There are many enduring controversies within science, and they are fun to follow. There are raging debates about the so-called Hobbit or Homo floresiensis, is it a new species or a diseased human? You may be surprised to hear that there is still a controversy over whether or not the dinosaur extinction was due to a meteor impact or other terrestrial factors (although I think this one is heavily tilting toward the impact theory).
One controversy I have been following, here and on the SGU, concerns the Young Dryas and whether or not the cooling characteristic of that period was due to melting glaciers or a local comet impact.
Such controversies always raise a few general issues for me. The first is how the mainstream media covers them, which I always find disappointing. Properly covering genuine scientific controversies is challenging, but that is what science journalists are supposed to do. What I find is that they tend to present each new study in the debate as if it is definitive and has ended the debate, rather than putting it into the proper context of the ongoing controversy.
Another common mistake is to rely on one expert rather than getting a reasonable sample. They tend to weight the story toward the side of the expert on which they relied, and maybe provide only token coverage of other views. There is also, of course, the issue of proper balance. Reporting should reflect the balance of opinion in the scientific community. It’s OK to present minority opinions but they should be presented as such.
Another issue I find interesting is the relationship between different types of explanatory systems. In this case we are seeing a specific example of the greater debate between gradualism and catastrophism – are current geological features explained by gradual processes over millions of years or by sudden dramatic events? The history of geology started out far to the catastrophe end of the spectrum, influenced by stories of the great flood. But then the pendulum swung far to the gradualism end of the spectrum, which became dogma for many decades.
Now, as if often the case, it is recognized that both views are correct – there are gradual processes that are punctuated by occasional catastrophes.
With all that in mind, let’s take a look at the Younger Dryas. The last glacial maximum ended about 20,000 years ago. That glacial period was followed by interstadial (warm) periods and stadial (cold) periods. The term Dryas refers to the indicator genus (Dryas octopetali) which is a tundra flower that was much more widely distributed during cold periods. Its pollen in core samples is therefore a good indicator of a stadial period.
Following the last glacial period there were three Dryas mini-cold periods, the Oldest Dryas from 18,000-15,000 bp, the Older Dryas from 14,000 to 13,700 bp, and the Younger Dryas from 12,800 to 11,500 bp.
The Younger Dryas also coincides with the extinction of much of the North American megafauna (like the mammoths) and the Clovis culture. The Clovis, named after Clovis, New Mexico, are a paleoindian culture defined by their distinctive stone spear points. They were big game hunters, so it’s not surprising that the Clovis industry went away with the big game (it’s not clear if the people went away, or just their hunting culture, which had to be replaced with a small game culture).
The Younger Dryas was not only cold, it turned North America into a dry, windy, and inhospitable place. The controversy is over what triggered the Younger Dryas. There are two main theories. The first is that the melting of the North American ice sheet at one point opened a river of fresh water into the north Atlantic ocean. The sudden dumping of massive amounts of fresh water into the Atlantic reduced its salinity and shut down the ocean currents that bring warm tropical waters north, warming the continent. This lasted until the ice sheets melted and the fresh water river stopped.
The more recent rival theory is that a comet impact in present day Canada threw up dust and triggered extensive continental cooling. In 2013 a major study in support of this theory was published. They found:
Now, in one of the most comprehensive related investigations ever, the group has documented a wide distribution of microspherules widely distributed in a layer over 50 million square kilometers on four continents, including North America, including Arlington Canyon on Santa Rosa Island in the Channel Islands. This layer –– the Younger Dryas Boundary (YDB) layer –– also contains peak abundances of other exotic materials, including nanodiamonds and other unusual forms of carbon such as fullerenes, as well as melt-glass and iridium.
Critics of the impact theory, however, has recently replied with yet another study, this one looking at the Younger Dryas Boundary layer in Syria. The authors write:
Siliceous scoria droplets, measuring from 1 to 10 mm, from one late Pleistocene and four early Holocene archaeological sites in northern Syria are compared to similar droplets previously suggested to be the result of a cosmic impact at the onset of the Younger Dryas global cooling event. The findings demonstrate that the presence of siliceous scoria droplets are independent of age and thus are not specific to the beginning of the Younger Dryas. Occurrences have not been reported from natural deposits, but are instead associated with buildings destroyed by fire and thus appear to be restricted to archaeological sites. We therefore conclude that melting of building earth in ancient settlements can occur during fires reaching modest temperatures. There is no evidence to suggest that siliceous scoria droplets result from very high temperature melting of soil and are the result of a cosmic event.
Therefore, at least in Syria, some of the evidence used to support the impact theory may instead come from ancient house fires. The authors further point out that the droplets were formed of local dirt, not dirt from another continent, that the droplets were mot likely formed from modest heat (rather than the intense heat of an impact), and that they were spread out over 3,000 years (not one moment in geological time as would be expected from an impact).
Impact theorists, however, have other lines of evidence on which to stake their claims, and this is certainly not going to end the controversy.
The reasons for the ongoing controversy include that fact that there are many independent lines of evidence, no one of which is definitive, and they can point toward different conclusions. There are also different interpretations of these lines of evidence.
It is also possible that the history scientists are trying to reconstruct is in reality more complex than either theory currently states. Perhaps, for example, there was a meteor impact around the time of the Younger Dryas, but it was small and didn’t trigger the Younger Dryas.
In any case, I love reading about scientists engaging in such narrow debates. They are passionate, often brutal, but in the end focus on the evidence. All sides may have picked a pony, but ultimately they want to discover the truth and will have no choice but to listen to the evidence. Such debates also show how clever scientists can be, as they search for alternative explanations and subtle ways of interrogating the evidence.
Such controversies also reveal the caricature of science and scientists often presented by science deniers and anti-scientists. They try to portray scientists as dogmatic, closed minded, and lacking in imagination. Nothing could be further from the truth. Following these narrow science controversies, ones that do not have huge political or ideological implications, in a way is like observing scientists “in the wild.” We get to see how they think and operate when they are not acutely aware that anyone is really paying attention.
Registration for NECSS, the North East Conference on Science and Skepticism is now open. Included in the program will be a day of Science-Based Medicine.
Speakers will be Harriet Hall, Jann Bellamy, David Gorski, Steve Novella and Mark Crislip.
NECSS will be April 9–15, 2015 in New York City at the Fashion Institute of Technology. The SfSBM part of the program will be Friday, April 9 and you can attend one or more of the days. $95 for one day or $195 for the entire conference.
The precise program will be announced soon.
The Society for Science-Based Medicine is a co-sponsor of NECSS and paid SfSBM members can get a 15% discount using the code SFSBM2015.
Humans have a massive footprint on our ecosystem. Enough so that we have to think carefully about anything we do on a large scale, such as agriculture, industry, shipping (because of invasive species), and using drugs to fight bacterial infections.
The development of antibiotic resistance is a particular worry of mine, and one that I feel does not get proportional attention in the media. It is quite possible that in the future more people will die from antibiotic resistant bacteria than global warming, food shortages, or disrupted ecosystems (depending on how each of these things develop).
We are already seeing more deaths from drug-resistant bacteria, longer hospital stays, and greater costs. I have seen this change during my career. When I round in the hospital I now have to don protective garments before entering many patient rooms because they are infected or even just colonized with a resistant strain of bacteria.
There is no way around the fact that were are engaged in a war with the subset of bacterial species on this planet that are capable of infecting humans. We have been winning for a while, but the bacteria are now rallying.
Antibiotics either stop bacteria from reproducing (bacteriostatic) or kill them outright (bacteriocidal) by disrupting some aspect of their biology that is different than eukaryotic cells (the kind of cells that comprise multicellular organisms like people). The problem is evolution – random mutations can change the targets of the antibiotics in order to make the bacteria resistant. During a single infection bacteria may reproduce billions of times, offering many opportunities for such mutations. The antibiotic then provides the selective pressure, allowing the resistant bacteria to survive, and perhaps even fine tune their resistance.
Making matters worse, bacteria can easily swap genetic information through plasmids, little circles of DNA, and so one resistant strain can share their resistance with others. In fact plasmids that contain the ability to resistant multiple antibiotics can be swapped and selected for, even if only one of the resisted antibiotics is being used.
This is all unavoidable, but is worsened by overuse of antibiotics or improper use of antibiotics, for example using a broad spectrum antibiotic instead of a targeted narrow spectrum drug. Resistance is also worsened when patients stop their antibiotic regimen prematurely allowing resistant bacteria to bounce back.
The worst-case scenario is that we will enter a post-antibiotic era where humanity is plagued by a host of completely resistant bacteria. Right now we are moving in that direction, as bacteria are evolving resistance faster than we are developing new antibiotics. The FDA has not approved a new class of antibiotics (one that works on a new target, rather than just a new version of an existing class) for almost thirty years (since the late 1980s).
There are, however, several potential new antibiotics in the pipeline. One new drug is making headlines because of a recent Nature article publishing early research, and because of a novel mechanism of antibiotic discovery. The drug is teixobactin, which disrupts the cell membrane of some bacteria. It is potentially effective against gram-positive, but not gram-negative bacterial species.
There are two encouraging aspects of this research. The first is that the researchers, Lewis et. al. developed a new assay to screen for possible antibiotic compounds. Many antibiotics were discovered by culturing bacteria from soil to look for those that inhibited the growth of infectious bacteria (some bacteria produce compounds that inhibit the growth of other bacteria). However, only about 1% of soil bacteria can be cultured, and that pool has been mined long ago.
Lewis and his fellow researchers developed what they call an iChip which is capable of culturing the other 99% of soil bacteria. The chip contains hundred of little chambers containing soil that would allow for bacteria to be culture in their required environment. After the bacteria are cultured on the chip they are overlayed with a gel containing either Staphylococcus aureus or Mycobacterium tuberculosis (two bacteria that cause infections in humans). If a colony fails to form over one of the chambers, then the bacteria growing in that chamber may be producing an antibiotic.
They have already screened over 10,000 bacteria in this way, discovering many potential antibiotics, including teixobactin. This technique may therefore lead to the discovery of many new antibiotics.
The second reason for optimism is that, so far, none of the Staphylococcus aureus or Mycobacterium tuberculosis tested showed any resistance to teixobactin. This does not mean resistance will never develop, but hopefully it will mean the antibiotic will remain effective for at least decades.
The caveat here is that this is pre-clinical research only. The drug now needs to be tested in animals and then humans. Many potentially very useful drugs die at the early clinical stage because it is discovered they have some toxicity. Drug companies may still synthesize different versions of the drug, trying to reduce toxicity or change it pharmacological properties, and that could add many years to development with no guarantee of an approved drug at the other end.
There are three other antibiotics in the pipeline with novel mechanisms of action. One is brilacidin, which is described as a peptide mimetic, because it mimics a protein used by our immune system to attack bacteria. This drug is in early human trials, but is still several years away from approval if all goes well. The company, Cellceutix, claims the drug is broad spectrum, rapidly bacteriocidal, with a low potential for resistance.
There are also two new beta-lactamase inhibitors, avibactam (Forest Laboratories) and MK-7655 (Merck). These are also in early clinical trials, meaning that if all goes well they are 3-5 years from approval.
These new drugs are encouraging, but again there is no guarantee any of them will make it through the research process.
The evolution of bacterial resistance is a major problem for our civilization. I know we face many challenges, and this is just one, but every expert I talk to or read seems to be expressing the same opinion – this is very serious and we are not paying enough attention to this problem.
We need to continue to improve standard practice in terms of antibiotic use to minimize resistance, to educate the public about the importance of proper antibiotic use, and to research novel mechanisms for fighting bacterial infections.
The situation is not hopeless. We just need to keep ahead of the curve. At some point we may need to take existing antibiotics off the shelf and allow resistance to fade so that we can then cycle them back in in the future.
As with many of these long term problems facing our civilization, we need to start thinking in terms of a sustainable strategy. There may always be game-changing technology in the future, but we can’t predict or count on such technology, so for now we need a sustainable solution.
I read a lot of the pseudo-medical websites. The writing is at best pedestrian, often turgid, and, at its worst, incoherent. It is rarely is either engaging or clever.
Wit, the clever bon mot, the amusing turn of phrase or retort is rare at best. So rare I cannot think of an example. It is ironic that those who engage in fantastical treatments are so often lacking in cleverness with language and thought. The closest you get to humor are the painfully lame cartoons at the Natural News. I am sure that the readers will flood the comments with examples of all the clever writing I have missed in the world of pseudo-medicine just to prove me wrong. Not that the reality-based world is much better. It is the rare author on the internet whose style keeps me coming back for more.
For some reason I found Dear Science Based Medicine, Just a Few Questions About Acupuncture funny and engaging, at odds with most of the purple quasi-paranoid articles I normally read. Just the right amount of chatty snarkiness to be enjoyable, at least for me. So refreshing given the style of the usual pro-acupuncture comments. Your millage may vary.
I thought when reading the article that I would enjoy discussing acupuncture over a beer with Mel. And may I call you Mel? It is how you signed the entry, but I do not want to be creepy, so I am a find and replace away from changing it to Ms. Koppelman. If there is any personality in an article I tend to form a totally erroneous mental picture of the writer. Oh, and sorry Mel, the first few times I read the article I didn’t look at your bio or picture (it was on a phone) and assumed Mel was a male name. My bad. It says something about my biases, n’est pas?
Mel asks many questions of SBM and I will try to answer them as best I can, although I lack the time to reply to all of them. And I will take the opportunity to ask some of my own questions as well. Mel can have a part two to her article. The gift of blog fodder keeps on giving.
Before she gets to the questions, Mel makes a key statement:
I now understand that the positive results I see in practice are due to the subjective impression of improvement without actual improvement and the lack of a controlled setting and basically people in general being, how do you describe them? Kinda simple and a bit moronic? I mean, people actually think that they’re in less pain, sleeping better, feel better in themselves, pooping more when they were constipated, pooping less when things were moving too quickly, taking less medication, and taking fewer days off of work, etc etc. What a bunch of gullible dodo brains, am I right? That post hoc, ergo propter hoc gets them over and over (and over and over) again. Poor dears.
To be clear I never think of users of pseudo-medicine as ‘kinda simple’ or a ‘bit moronic’ or as having ‘gullible dodo brains’. Mel: can you give me a half dozen examples from the bloggers (as opposed to the commenters). I would be curious of an example. Oh yeah. Food Babe. But as my kids would say, based on her content, objectively those adjectives may very well apply. So besides Food Babe.
While I may think acupuncture is a bit moronic, I (and I would wager my colleagues as well) do not have the same opinion of most of its users or practitioners. I try hard in my dotage to disparage the message, not the messenger, but I have no doubt you can find examples where we have referred to those who use acupuncture as some version of idjit.
Proponents of most pseudo-medicine are human and, like me, are at risk for the innumerable ways, the cognitive biases, that make our interpretation of causality suspect. We are horrible at understanding reality. Being wrong does not make a person a gullible dodo brain. Only wrong. Otherwise we would all be dodo brains, perhaps a poor example.
So Mel, I would ask the question, what criteria would you use to judge whether a therapy works? Subjective endpoints? Objective endpoints? Personal experience? Careful clinical trials?
And what do you mean by works? When I say acupuncture does not work, I mean it does not alter any primary anatomical or physiologic processes causing the disease in question. Do patients perceive benefit from acupuncture or other pseudo-medical therapies. You bet. Like all effective placebos, it can have positive psychological effects. Interactions with other, caring humans have perceived benefit, the same benefit that occurs when a child has a boo boo kissed or two apes groom each other.
And Mel, how would you control for the endless ability of people to see what they want to see, to have their biases confirmed. To quote the masters
There’s an old saying in Tennessee — I know it’s in Texas, probably in Tennessee — that says, fool me once, shame on — shame on you. Fool me — you can’t get fooled again.
or perhaps more coherently
The first principle is that you must not fool yourself — and you are the easiest person to fool.
I always remember N-Rays: at the beginning of last century some physicists ‘saw’ a new form of radiation that made no sense based on the understanding of radioactivity and published 100’s of articles in the physics journals. The researchers continued to see N Rays even after the machine was disabled without their knowledge; it turned out N Rays were a figment of their imagination.
And that is in the hardest of the hard of sciences, experimental physics. When ever I see an alleged therapeutic effect, due to a pseudo-medicine or a reality-based intervention, I always ask if they are publishing the equivalent of N Rays. And a good deal of the time, unfortunately, they are.
I would note up front that Mel and I differ in our standards: I never, ever, trust my experience for determining if a therapy is effective. There are too many ways I can be fooled into thinking what I am doing is effective. It is why the three most dangerous words in medicine are “I lack insurance.” No. Sorry. In my experience. And I remember everyday that I am the one most likely to be fooled by my experience.
It is why I generally trust independent studies where bias is removed and the endpoint is not dependent on the whims of the patient and researcher: the double blind placebo controlled trial. One of the issues I look for in acupuncture trials is whether the patient and researcher were blind and if the blinding was successful, since there is
pronounced bias due to lack of patient blinding in complementary/alternative randomized clinical trials with patient-reported outcomes.
Lack of blinded outcome assessors in randomized trials with subjective time-to-event outcomes causes high risk of observer bias. Nonblinded outcome assessors typically favour the experimental intervention, exaggerating the hazard ratio by an average of approximately 27%
Warping bias can even happen in animal studies:
Lack of blinding of outcome assessors in animal model experiments with subjective outcomes implies a considerable risk of observer bias.
Combine the above with the issues of placebo effect and bias for pain
We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important.
And I conclude that it can be very difficult to know if therapeutic effects are real if blinding is not fastidious, especially if the endpoints are subjective. People see what they want to see.
So Mel, I ask, since we here at SBM are often called arrogant, although not by you I hasten to add. What is more arrogant given the sins to which memory is prone, those who rely on their experience or those who are skeptical of that experience?
Why do you trust your experience as valid given all the potential biases that could be coloring your perception of efficacy? In other words, Mel, how do you know that you are not seeing N Rays when you see acupuncture efficacy?
On your site, you define acupuncture as “the practice of placing very thin needles through the skin in specific locations of the body for the purpose of healing and relief of symptoms.”
Mel does not object to the definition; it describe acupuncture but is inadequate, so I would ask, as long we are asking questions, Mel are all 30–40–50 styles of acupuncture equally legitimate: Chinese, Japanese, Korean, Ear, Wonli etc. etc. etc.
I ask because as I understand diseases, such as ‘pain, sleeping better, feel better in themselves, pooping more when they were constipated, pooping less when things were moving too quickly’ as due to the result of different physiologic processes and anatomy.
The causes of insomnia are different than the causes of diarrhea, and each can have multiple different potential etiologies. The insomnia of existential angst and guilt (am I over sharing?) is not the same as too much coffee. The constipation of hypothroidism is not the constipation of narcotic abuse.
From my reductionist reality-based approach to disease, each process would require a different intervention. Different mechanisms result in different treatments of the underlying process. And yes, I try to treat underlying processes, not symptoms. If all forms of acupuncture are equally effective for all forms of healing and relief of symptoms, then what is the underling mechanism? Because I cannot see needles in the skin having an effect of such a wide variety of fundamentally diverse processes. Or any process for that matter, at least based on known anatomy and physiology.
According to the World Health Organization, the following are amenable in some way to acupuncture (Mel, any you disagree with?)
Diseases, symptoms or conditions for which acupuncture has been proved—, through controlled trials—to be an effective treatment:
Adverse reactions to radiotherapy and/or chemotherapy, Allergic rhinitis (including hay fever), Biliary colic, Depression (including depressive neurosis and depression following, stroke), Dysentery, acute bacillary, Dysmenorrhoea, primary, Epigastralgia, acute (in peptic ulcer, acute and chronic gastritis, and, gastrospasm), Facial pain (including craniomandibular disorders), Headache, Hypertension, essential, Hypotension, primary, Induction of labour, Knee pain, Leukopenia, Low back pain, Malposition of fetus, correction of, Morning sickness, Nausea and vomiting, Neck pain, Pain in dentistry (including dental pain and temporomandibular, dysfunction), Periarthritis of shoulder, Postoperative pain, Renal colic, Rheumatoid arthritis, 23 Acupuncture: review and analysis of controlled clinical trials, Sciatica, Sprain, Stroke, Tennis elbow,
Diseases, symptoms or conditions for which the therapeutic effect of, acupuncture has been shown but for which further proof is needed:
Abdominal pain (in acute gastroenteritis or due to gastrointestinal spasm), Acne vulgaris, Alcohol dependence and detoxification, Bell’s palsy, Bronchial asthma, Cancer pain, Cardiac neurosis, Cholecystitis, chronic, with acute exacerbation, Cholelithiasis, Competition stress syndrome, Craniocerebral injury, closed, Diabetes mellitus, non-insulin-dependent, Earache, Epidemic haemorrhagic fever, Epistaxis, simple (without generalized or local disease), Eye pain due to subconjunctival injection, Female infertility, Facial spasm, Female urethral syndrome, Fibromyalgia and fasciitis, Gastrokinetic disturbance, Gouty arthritis, Hepatitis B virus carrier status, Herpes zoster (human (alpha) herpesvirus 3), Hyperlipaemia, Hypo-ovarianism, Insomnia, Labour pain, Lactation, deficiency, Male sexual dysfunction, non-organic, Ménière disease, 24 3. Disease and disorders that can be treated with acupuncture, Neuralgia, post-herpetic, Neurodermatitis, Obesity, Opium, cocaine and heroin dependence, Osteoarthritis, Pain due to endoscopic examination, Pain in thromboangiitis obliterans, Polycystic ovary syndrome (Stein–Leventhal syndrome), Postextubation in children, Postoperative convalescence, Premenstrual syndrome, Prostatitis, chronic, Pruritus, Radicular and pseudoradicular pain syndrome, Raynaud syndrome, primary, Recurrent lower urinary-tract infection, Reflex sympathetic dystrophy, Retention of urine, traumatic, Schizophrenia, Sialism, drug-induced, Sjögren syndrome, Sore throat (including tonsillitis), Spine pain, acute, Stiff neck, Temporomandibular joint dysfunction, Tietze syndrome, Tobacco dependence, Tourette syndrome, Ulcerative colitis, chronic, Urolithiasis, Vascular dementia, Whooping cough (pertussis)
That is one hell of a list Mel. How can needles in the skin have so many effects? What is the mechanism that ties them all together, the one ring to bind them, the commonality underneath acne, schizophrenia, Whooping cough and excess saliva? Or is there a different mechanism for each disease? To my way of thinking either these all have the same underlying mechanism to provide healing from acupuncture OR it is all N-Rays. Which brings us to the quote
But when you say that acupuncture doesn’t work, the main argument you repeat over and over (and over and over again) is that acupuncture doesn’t work because there’s no such thing as qi.
It is, by the way, a side comment but when writing a blog entry do you presume that the reader has the background of all the prior blog entries or should the entry be self contained? I choose self contained, and that does lead to lots of repetition. As this entry no doubt confirms.
Mel: if there is no qi, how does so many one process (needles in the skin) accomplished dozens of different ways (Chinese, Japanese, etc) effect so many radically different processes? Seems far fetched to me.
Mel continues with a good point:
Whether or not inserting and stimulating small needles for therapeutic benefit is effective for symptom reduction or disease resolution really doesn’t rely on the existence of qi as an explanatory model.
That is true. Acupunctures could work for both infertility and pain as well everything else on the list from as of yet unknown underlying unified mechanism. Because I can’t see how acupuncture could work for all those processes based on what we do know about anatomy and physiology.
But the plausibility the mechanism is important if you are Baysean kind of gal. If you have an implausible intervention then any efficacy is likely to be a false positive and due to bias/poor methodology
Needles in the skin to alter constipation and fertility and acne and schizophrenia seems highly implausible. And as much as Bayes makes my head hurt, it appears to be the way the world works, so that it is highly probable that any effect of acupuncture is likely bias.
Smarter people than I have written about Bayes and its application of pseudo-medicine. There is some arbitrariness to deciding prior plausibility. But given the above discussion of the issues of bias and the difficulty in ascribing one therapy with such a multitude of effects, you can see how I could rate the prior plausibility of acupuncture as close to zero as you can get without reaching it. And in your essay you do not offer compelling reasons I should change my mind.
You’re basically saying that in order for sticking needles into someone to have a therapeutic effect, then qi must exist and if qi doesn’t exist, then acupuncture has no therapeutic benefit.
Yes and no. I am saying that if qi does not exist than you have no mechanism to account for the effects of acupunctures on a multitude of processes that are all fundamentally different. You have no reason for a specific effect on a specific process.
That is different from a therapeutic benefit. To repeat my favorite metaphor, acupunctures are beer goggles: it gives the appearance of improvement with no actual change. Kind of a zen koan, huh? Although the only thing I got out of my time in the Zen temple in Kyoto all those years ago was a welt on the back from being hit by a board during meditation to shock me into enlightenment. Fail.
Penicillin will cure S. mitis endocarditis every time, whether you believe in germs or not. Acupuncture works best when the patient believes they are getting acupuncture and believes that acupuncture is effective. When a therapeutic effect depends primarily on belief it suggests that any effect on the WHO list is illusory given the lack of a reasonable mechanism.
But Mel you remain vague throughout, and vagueness is a wee bit harder to discuss than specifics. What then is acupuncture, and which style and how does it work and for what process?
One of your main arguments against acupuncture is that it “lacks a plausible mechanism.”
But you also argue that the copious amount of research into acupuncture’s mechanisms is “not relevant to the argument” of whether or not acupuncture works. I find this really confusing because you say that “basic science considerations are, in essence, ignored in determining whether there is
sufficient prior scientific plausibility of acupuncture to treat, for instance, infertility (1) or depression (2), and equivocal, bias-prone clinical trials are ranked much higher than the basic science considerations that make the hypothesis that acupuncture can do anything for infertility so implausible as to border on impossible, barring new evidence speaking to its plausibility.”
So, if I understand you correctly, you’re saying that acupuncture as a treatment modality is implausible but you’re not going to look at the research that explores its plausibility because it’s irrelevant to the argument? In order to take a “science-based” approach to the question of acupuncture’s biological plausibility, you are going to make a conscious decision not to evaluate the research into its effects on
the brain using fMRI studies, purinergic signalling, autonomic tone using heart rate variability, effects on gene expression using high throughput metabolimics, and mechono-transduction studies compared to sham. That’s an interesting stance to take.
Assuming of course that these results are valid. To paraphrase another
According to Professor John Ioannidis’ very well-respected and highly cited article on research methods, most published research findings are actually false.
Yep, you read that correctly.
For a variety of reasons, including funding sources, poor research design, and good old bog standard bias, most published research findings end up being unrepeatable and/or overturned. And it is on these very results that the entire institution of medical acupuncture is poised. Shaky foundations, indeed. When your acupuncturist prescribes you a needle or recommends an herb, assuming that these decisions are even based on the most up to date and highest quality research, there’s a good chance that those conclusions will be shown to be flat out wrong in due course.
Sobering, ain’t it?
Yep. Sobering. Most of the positive research on acupuncture is likely wrong.
As you note later that
Wow, that’s a very … nuanced position. I feel relieved that the good people of Science Based Medicine are equipped to tease out these subtleties
Nuance is important in these issues. The devil, and the fascination, is in the details of a topic. Precision of language hopefully reflects precision of thought, so here’s hoping I can be precise and clear. Wish me luck.
Sticking needles in animals, especially as part of healing ritual in humans, is going to have local effects and effects in the brain. So will stubbing your toe. The question is whether it is more than the effects of the needle in the skin and results in altering the panoply of processes the WHO says are amenable to treatment from acupuncture.
I see the literature about the alleged mechanism(s) of acupunctures as than the literature of the effects of poking needles in the skin. It has no wider applicability to treating any disease or symptom, the raison d’etre of acupuncture
So Mel, how do those fMRI studies, purinergic signalling, autonomic tone using heart rate variability, effects on gene expression using high throughput metabolimics, and mechono-transduction studies compared to sham shed light on mechanism for using acupunctures for stroke, leukopenia and depression? Or the GI issues noted in your opening statement.
And I wonder. As I understand it, in TCM the diagnoses for which acupuncture is used is based on tongue and pulse characteristics. Mel, just how do you translate the tongue/pulse diagnosis to reality-based diagnosis and fMRI and purinergic signalling as examples?
Any mechanistic studies about acupuncture that you have managed to read that do show a plausible mechanism don’t actually address acupuncture, just the insertion of tiny acupuncture needles in an acupuncture treatment-reminiscent fashion. Got it.
Correct. By Jove, I believe she’s got it. The nee(dle) near knee does nothing to the qi. The pin near the shin does nothing… The point near the joint…. I really should edit that out… Trying way to hard but so close…
And think back to N Rays. They had all sorts of research and theories to explain how N rays worked. Or cold fusion. If the the effect you are seeing is an illusion, then the research explaining it is either an illusion or, more likely, irrelevant.
Harriet coined the term tooth fairy science:
Tooth Fairy science” is an expression coined by Harriet Hall, M.D., (aka the SkepDoc) to refer to doing research on a phenomenon before establishing that the phenomenon exists…Fairy Tale scientists mistakenly think that if they have collected data that is consistent with their hypothesis, then they have collected data that confirms their hypothesis. Tooth Fairy science seeks explanations for things before establishing that those things actually exist. For example:
You could measure how much money the Tooth Fairy leaves under the pillow, whether she leaves more cash for the first or last tooth, whether the payoff is greater if you leave the tooth in a plastic baggie versus wrapped in Kleenex. You can get all kinds of good data that is reproducible and statistically significant. Yes, you have learned something. But you haven’t learned what you think you’ve learned, because you haven’t bothered to establish whether the Tooth Fairy really exists.
Given issues of prior plausibility and issues of bias in studies, I am more inclined to see such explanatory studies through the lens of tooth fairy science.
By assigning a low prior plausibility score to acupuncture, any positive studies now magically have very little positive predictive value – in other words the chances that a positive study is a true, rather than false positive, are inversely proportional to the prior plausibility value that you made up off the top of your head without reading the literature! Bravo!!
You got it. Perfect. You do understand. Except for the reading the literature part. I did. You just cannot apply it to your own practice.
Mel continues with
Pragmatic studies – Better to be a skeptic with a migraine than a pain free idiot, am I right? (Up high!!)
If we take a condition like migraines, for example, we see in double blind RCTs that needling acupuncture points is roughly equal in effectiveness as needling non-acupuncture points and that both of these are very very effective, indeed.
The classic interpretation is that if an intervention is no better than placebo, it does nothing specific for the process being treated and you are seeing the sum total of the nonspecific and usually beneficial effects of a medical intervention aka the placebo effect.
My favorite example is internal mammary artery ligation, which was used for angina in the 1960’s until it was shown that fake surgery had the same effects as the procedure.
Mel: How would you interpret the internal mammary artery ligation studies and, more importantly, how would you apply it? By your interpretation should we still being doing internal mammary artery ligation?
Or arthroscopic partial meniscectomy? Both are equal to a sham procedure. Look at the graphs: real and sham surgery had an equal decrease in their knee pain, about 50%. About the same degree of effect you credit to both real and sham acupuncture. As a Gedankenexperiment lets ignore the specifics and say acupuncture and arthroscopic partial meniscectomy cause an equal (50%) decline in knee pain and ignore the cost/risk/morbidity of surgery. So would you say arthroscopic partial meniscectomy works for knee pain as well as acupuncture and should be used? And how about sham arthroscopic partial meniscectomy? I mean, if you wanna be all ‘pragmatic-study’ about it?
Although not done, I would wager both sham and arthroscopic partial meniscectomy are better than wait list or medical therapy. The more complicated the placebo the larger the effect. I see all of them as not working: not effecting a specific anatomical or physiologic process. They do have beneficial effects. They are placebos. Like acupuncture.
It is one of the ongoing ethical/interesting questions. Are placebos ethical? I think no, since to use them requires lying to the patient.
And if you’re saying that these studies show that acupuncture doesn’t work because acupuncture and minimal acupuncture are similarly effective, what do they say about the pharmaceuticals?
Some pharmaceuticals are often overrated in their effects? Water is also wet and fire is hot. The numerous issues with modern medicine and the perversion of clinical trials are a different question. It is the “there are issues with airlines, so lets use flying carpets” argument.
Don’t you like people and want to learn more about what’s effective in making them better?), doesn’t it at least make you ask a couple of questions about the so called “science-based medical treatment” and why it’s not more effective than “SCAM” (as you so cleverly call it) in the real world? I mean, if being nice to someone for an hour a week while duping them into buying expensive woo is more effective than science-based medical drugs, with all the risks that they entail, then shouldn’t that be further explored? I mean, if you wanna be all ‘science-based’ about it?
I suspect you are using the term ‘duping’ ironically as is the rest of the sentence, but at a fundamental level that is how I un-ironically see virtually all the pseudo-medicines discussed on this site, except the duping part, which implies willfully fooling people.
Which again raises interesting questions of approach to health care. Here is mine.
My job as a physician is accurately diagnose my patient, tell the patient what is going on, what their options are and make them better if I can. They have entrusted me with their health, their life, their hope, their money and their time, all of which are precious and I take that responsibility very seriously. Although an atheist all my life, I curiously see being in health care a calling, although a calling to what I will be damned if I know. Pseudo-medicines like acupuncture can and do waste health, waste time, waste money, waste hope because at their core they are N Rays.
So no, it shouldn’t that be further explored. The answer to bad medicine is to improve it, not to explore magic systems divorced from reality.
Don’t you like people and want to learn more about what’s effective in making them better?
Mel. Mel. Mel. Such a wonderful snarkfest ruined by disparaging the motives of messenger rather than message, albeit a minor example. I have to admit it fries my bacon, gripes my cookies or whatever angry food analogy that whips your smoothie. I am proud of the work I have done for the last 33 years and have always strived to do the best I can for my patients. I do this gig, and medicine, because I hope I am a caring, committed health care provider whose primary motivation is help my patients. Certainly that is true of almost every HCW I have known, reality-based or otherwise. But that is another difference between pseudo-medicine providers and those of us at SBM, we usually do not presume malign intent. I think you are wrong about acupuncture, but I presume your motives are beneficent. But as someone said
some haters always gonna hate. That’s ok, we’ll let them.
I know. Boo hoo, poor poor pitiful me. I have an issue, where is my tissue?
Mel has more questions and I lack the time to address them further. I have a finite time for SBM and need some time with my family and other parts of my growing multi-media empire. I usually do the final draft Thursday nights but with my eldest off for his final semester of college I will be taking him out for dinner instead of answering the rest of your questions. Damn. Time does fly.
Mel, I hope that helps answers at least some of your questions. I also learn a lot by writing these articles and I hope you did too.
I do not think we will ever agree, but I enjoy your style on the blog even if I do not agree with the content. I look forward to your answers and, I hope, at least one laugh at my expense.
All the best to you as well,
Recently Eric Metaxas wrote an opinion piece in the Wall Street Journal in which he argues that, “Science Increasingly Makes the Case for God.” (Sorry, it’s behind a paywall, but I will quote the salient parts.) Metaxas is an author and speaker, but not a scientist, and it shows in his writing.
His essay is based on two instances of the anthropic principle, which simply notes that in order for life to exist the universe must possess conditions compatible with life. He applies the anthropic principle to the earth specifically and to the universe as a whole. Starting with the earth he writes:
As factors continued to be discovered, the number of possible planets hit zero, and kept going. In other words, the odds turned against any planet in the universe supporting life, including this one. Probability said that even we shouldn’t be here.
Today there are more than 200 known parameters necessary for a planet to support life—every single one of which must be perfectly met, or the whole thing falls apart. Without a massive planet like Jupiter nearby, whose gravity will draw away asteroids, a thousand times as many would hit Earth’s surface. The odds against life in the universe are simply astonishing.
He states this as if it is an accepted scientific fact without any kind of reference. It is hard to know, therefore, exactly what he is talking about. What are these 200 known parameters? The only references I can find to such a claim is from Christian apologist sites trying to make the case for god, as is Metaxas.
This site, for example, lists 68 parameters. In them we can see the error in logic that this line of argument is making. First, Metaxas is being imprecise with his wording. He is referring to “advanced life,” not any life. If we assume that he is talking about complex life as it exists on earth, he is still making a massive error in logic – a common error referred to as the lottery fallacy.
Essentially Metaxas and other apologists are asking the wrong question – what is the probability of the kind of life found on earth coming into existence. This is like asking what the probability is of John Smith winning the lottery, rather than asking the better question, what is the probability of anyone winning the lottery.
Of course life on earth is fine-tuned for and takes advantage of conditions on earth, because that is where it evolved. Lawrence Krauss correctly points out in an open letter to the WSJ:
This is more likely an example of life being fine-tuned for the universe in which it evolved, rather than the other way around.
We only have one example of life. It seems likely that there are very different beings on a very different planet in another part of the universe marveling at how well suited their environment is for them.
Going through lists of alleged parameters it is also clear that Metaxas is massively overstating his case. There is no reason to believe that each parameter (if it has to be met at all) has to be “perfectly met.” As we are increasingly learning from extremophiles, life can evolve to adapt to a wide range of conditions. Conditions that we would find hostile might be perfectly comfortable to life that evolved in those conditions.
In fact if anything over the recent decades scientists have discovered that life can probably exist over a much wider range of conditions than previously imagined. Life in the universe is getting more likely, not less.
Metaxas is also partly falling for an earth-centric bias. For example, we think of stars and therefore planets as existing within galaxies. However, in 2014 scientists discovered that as many as half of all stars exist in the space between galaxies. This just doubled the number of stars in the universe that can host planets and life. Also, life is probably safer between the galaxies, far away from gamma ray bursts and supernovae. Perhaps more life exists between galaxies than within them.
There are also more rogue planets in the galaxy than planets around stars. Conditions on rogue planets are likely to be very different from earth, but that doesn’t mean they can’t support complex life. Again, I can imagine beings on a rogue planet assuming incorrectly that life on a planet near a star would be impossible.
Assuming that every one of these alleged 200 parameters need to be perfectly met also makes many unwarranted assumptions. It ignores, for example, the role that life plays in the homeostasis of the environment.
Metaxas then follows up with:
There’s more. The fine-tuning necessary for life to exist on a planet is nothing compared with the fine-tuning required for the universe to exist at all. For example, astrophysicists now know that the values of the four fundamental forces—gravity, the electromagnetic force, and the “strong” and “weak” nuclear forces—were determined less than one millionth of a second after the big bang. Alter any one value and the universe could not exist. For instance, if the ratio between the nuclear strong force and the electromagnetic force had been off by the tiniest fraction of the tiniest fraction—by even one part in 100,000,000,000,000,000—then no stars could have ever formed at all. Feel free to gulp.
Multiply that single parameter by all the other necessary conditions, and the odds against the universe existing are so heart-stoppingly astronomical that the notion that it all “just happened” defies common sense. It would be like tossing a coin and having it come up heads 10 quintillion times in a row. Really?
This is just the old anthropic principle argument. Yes – the physical properties of the universe allow for complex life. But again Metaxas is committing the same lottery fallacy again.
It is possible that the laws of the universe are not random (as Metaxas is assuming with his coin-flipping analogy). Perhaps they have to be what they are for some deeper reason. We just don’t know.
It is also possible that there are many configurations of physical laws that allow for complex life (although very different from our own), and this is just one.
It is also possible that there are many universes, perhaps even infinite. In those universes where the laws are such that complex life is allowable, such life would consider itself highly unlikely – just like every lottery winner considers themselves extremely lucky and must marvel at the impossible odds that led to their win.
Metaxas’s arguments fail on multiple levels. I also found them not only unconvincing, but profoundly lacking in that he did not even acknowledge the counterarguments that are already out there. Either he ignored them or was unaware of them.
I also found his arguments an excellent example of motivated reasoning. He is trying a bit to hard to make the scientific case for god, grossly exaggerating his position and ignoring counterarguments.
We currently do not know how common life in general, complex life, or intelligent life is in the universe. There are simply too many variables, and we do not yet understand the full possibilities for which this universe might allow. The universe might be teeming with complex life. It is also quite possible that life as we know it on earth is very rare, perhaps even unique. As Sagan himself noted, someone has to be the first intelligent species in the universe, and they would correctly find themselves to be unique.
Perhaps we have won the cosmic lottery. That does not mean there is a purpose behind our existence.
I am happy to report some good news: chiropractors, naturopaths, acupuncturists and assorted other practitioners of pseudo-medicine didn’t fare too well in the 2013-2014 state legislative sessions.
We’ve been following their legislative efforts all year over at the Society for Science-Based Medicine. Some state legislatures meet in yearly sessions. At the end of the year, pending bills die with the session. Some meet only every other year. Others meet in two-year sessions and, in some of these, legislation introduced in one year carries over to the next year. All states with two-year sessions ended these sessions at the close of 2014, except New Jersey and Virginia. If you want to see how your state operates, several websites can help you: MultiState Associates, National Conference of State Legislatures and StateScape.Chiropractors
Chiropractors are already licensed in all 50 states and all of their practice acts permit the detection and correction of the non-existent subluxation. Having achieved that goal, the focus of chiropractic legislative efforts is to expand their scope of practice (the holy grail, for some, being primary care physician status), turf protection and mandates requiring insurance reimbursement or their inclusion in various activities, such as sports physicals, concussion treatment, and scoliosis detection programs.
The most interesting chiropractic bill, one from Oklahoma, didn’t fall into any of those categories:
Chiropractic physicians in this state shall obtain informed, written consent from a patient prior to performing any procedure that involves treatment of the patient’s cervical spine and such informed consent shall include the risks and possible side effects of such treatment including the risk of chiropractic stroke.
The Oklahoma Chiropractors’ Association thinks informed consent legislation is “dangerous.” According to Chris Wadell, President of the Oklahoma Board of Chiropractic Examiners, informed consent “isn’t needed.”
“We don’t hide from this but it just hasn’t been necessary to do it,” Wadell said. He insists that chiropractors are helping people and are being unfairly blamed for strokes after a patient’s neck is adjusted.
The bill was watered down to a “Task Force on Neck Manipulation.” It passed in the House but not the Senate.
Fortunately, a bill passed and was signed into law by the governor in Wisconsin requiring chiropractors (who already had a duty to obtain informed consent) to inform patients of reasonable treatment alternatives and the risks and benefits of those alternatives. It does not require disclosure of “extremely remote possibilities that might unduly alarm the patient.” The standard for determining what must be disclosed is that of a “reasonable chiropractor,” not what a “reasonable patient” would want to know. We’ll have to see whether chiropractors will inform patients of the risk of cervical manipulation from now on, since the official position seems to be that chiropractic cervical manipulation is not a cause of stroke at all.
Bills in New Mexico and Hawaii sought to expand the chiropractic scope of practice, but both failed. In New Mexico, which I’ve discussed before, chiropractors wanted to get their hands on even more drugs than their limited formulary already allows, which includes injection of “nutritional medicine,” bioidentical hormones and glandulars, among other substances. (They must have all of 90 additional hours of training for this privilege.) This time, they wanted to expand their formulary to include all drugs, including “dangerous drugs” (other than Schedule I and II) used in primary care practice. They’d need a “post-graduate degree in a clinical specialty” (not otherwise defined) for this, plus 650 hours in a supervised “clinical rotation” (again, not otherwise defined).
Both the New Mexico and Hawaii bills contained language which would essentially default to the chiropractic schools and boards to decide the chiropractic scope of practice. Of course, the bills don’t say that specifically. What they do say is that chiropractors could diagnose and treat any disease or condition for which they are “educated and trained” (New Mexico) or diagnose and treat with methods taught by chiropractic schools and approved by the state chiropractic board (Hawaii). Even though these bills didn’t pass, I think we are going to see more of this type introduced in the future, pressed by the “DC as PCP” faction. Like naturopathic schools, chiropractic schools could claim they train DCs to be primary care physicians, and thus they would – voila! – become PCPs under state law.
Chiropractors are threatened by physical therapists because PTs are educated and trained to use manual manipulation, but without all the mumbo-jumbo. In California, a bill failed that would have prevented PTs from performing joint manipulations, while in Washington, the governor signed a law that specifically allows PTs to perform spinal manipulations. The law has a comical provision that prevents PTs from using exactly the sort of mumbo-jumbo they avoid in the first place — “adjustments” and “maintenance or wellness manipulation.”
Finally, and thankfully, chiropractors won’t be performing mandated scoliosis screening in New York or sports physicals and commercial driver’s license exams in Washington. Those bills failed as well.Naturopathy
During 2013-2014, 10 naturopathic licensing bills were introduced, all of which attempted to give naturopaths a broad scope of practice. Treatments specifically permitted in some bills include colonic irrigation and prescription of “natural” medicines, vitamins, minerals and homeopathic substances, including administration by injection or IV. Pennsylvania would allow “visceral manipulation.” An interesting feature of many licensing bills is a provision allowing naturopaths to perform or order diagnostic testing, such as x-rays or those “commonly used” by MD PCPs, as long as it is “consistent with naturopathic education and training.” This is the same sort of open-ended permission we are seeing in chiropractic bills, defaulting to the schools to determine the scope of practice.
Eight of these naturopathic licensing bills were rejected (New York, Massachusetts, Michigan, Pennsylvania, Illinois, Iowa, Idaho, Rhode Island) leaving naturopaths licensed or registered in only 17 states and D.C. One bill, in New Jersey, is still pending because NJ is one of the two states to carry 2014 legislation over to 2015.
Only one licensing bill, in Maryland, passed, albeit with a scope far short of what they wanted. Maryland will not permit naturopaths to call themselves primary care physicians (or even “physicians,” for that matter). Nor will it allow them to prescribe drugs, use colon hydrotherapy or practice under the jurisdiction of their own board. Instead, they will be under the jurisdiction of the Maryland Board of Physicians, which is currently working on regulations, a subject I covered in a previous post.
Naturopaths also fought to have restrictions on their practice removed in Colorado. In 2013, after numerous attempts by naturopaths (also here), the legislature finally passed a registration (but not licensing) bill. The law prevents them from seeing patients under 2 years of age at all, and places severe limitations on their ability to treat patients between 2 and 8: they must disclose they are not physicians, recommend that the child have a relationship with a licensed pediatric practitioner, and give parents the CDC-recommended vaccination schedule. One of the main purposes of these restrictions was to thwart their efforts to dissuade parents from vaccinating their children. Fortunately, the bill watering down patient protections did not pass and those restrictions remain in place. On the other hand, a Colorado bill to eliminate their ability to prescribe drugs on their formulary and perform minor office procedures did not pass.
Another bill designed to protect patients was passed in Hawaii but only after having been defanged as it moved through the legislature. What began as a bill requiring that naturopaths who wanted to prescribe drugs have the same education as an MD or DO ended up as a law requiring more continuing education.
Naturopaths did get an expansion of their scope of practice in 3 states, but it was significant only in Connecticut, a topic I covered in an earlier post. (A humorous aside: There is a slide presentation, “About Naturopathic Medicine,” on the American Association of Naturopathic Physicians’ website comparing naturopathic “medical” school education to that of the Yale School of Medicine. You’re in good hands, Connecticut!) They can now practice “telemedicine” in Arizona and perform minor office procedures in Utah. A practice expansion bill in Alaska failed.Insurance Coverage
CAM providers crave coverage of their services by public and private health insurance. This can be a mixed blessing, since private insurers generally won’t cover diagnoses and treatments with insufficient evidence to support their use, such as many diagnostic and treatment methods used by chiropractors. This leads CAM practitioners to call on their friends in the legislature to force insurers to cover their services. (State mandates become more problematic under the Affordable Care Act, although the ACA has its own troublesome non-discrimination provision.)
Because bills mandating coverage are so numerous, we don’t follow them on SFSBM. One bill bears mentioning, though, because it is a good example of how CAM providers try to force themselves on health insurance programs via state legislatures.
Oregon created “coordinated care organizations” to provide health care services to Medicaid patients. Obviously, the state gets more value for the taxpayer dollar when ineffective treatments are excluded. So that is what the state did, by requiring that all CCO providers practice evidence-based medicine. Naturopaths, naturally, balked at this.
Not to worry, though. Legislators came to the rescue with a bill that required CCOs to include all state-licensed healthcare providers in sufficient numbers and geographical distribution to give all patients reasonable access. This would include
Reasonable access to chiropractic physicians [and] naturopathic physicians . . . for all primary care services that are within the scope of the provider’s license . . .
Acupuncturists would have to be included as specialty care providers.
The CCO would have to pay
. . . the same reimbursement rate for a service to all providers who are acting within the scope of their license . . . and may not vary reimbursement rates solely on the basis of a provider’s license . . .
Fortunately, this bill didn’t pass. Of course, CCOs can choose to include naturopaths, chiropractors and acupuncturists in their provider panels, they just won’t be forced to by the state. Nor will it have to pay the same rate it pays MD or DO physicians.Acupuncture, TCM and Oriental Medicine
Acupuncturists really struck out. Of the 7 acupuncture bills proposed, only one passed, and it wasn’t much. Pennsylvania acupuncturists must refer a patient to a physician if he treats a “condition” beyond 60 days. Now they can avoid referring if the patient doesn’t present with a “condition.” This is mystifying, because I can’t imagine why a patient would be getting acupuncture treatments at all if he didn’t have a “condition” that needed treating. The Pennsylvania House also passed a resolution making Oct. 24, 2014, “Acupuncture and Oriental Medicine Day,” because those modalities have been
used for thousands of years to diagnose and treat illness, prevent disease and improve well-being.
“Used,” maybe. Effective, no.
On a brighter note for consumers, the Pennsylvania acupuncturists must now carry $1 million in liability insurance, which will be enough to attract a personal injury attorney to take a plaintiff’s case should matters go south with the acupuncturist.
Speaking of going south, things did exactly that for acupuncturists in the Deep South. A licensing bill failed in Alabama, Louisiana wouldn’t even create a committee to look into licensing, and Mississippi refused to ditch a requirement that patients have a physician referral to see an acupuncturist.
Arizona didn’t pass a bill expanding the scope of “auricular acupuncture” to include PTSD treatment. A bill to create a “Traditional Chinese Medicine Traumatologist” certification passed the California Senate but not the House. If it had become law, these practitioners could treat musculokeletal conditions by stimulation of “acupressure points” to
open the body’s defensive chi and stimulate energy movement in the meridians.“Alternative Health Care Practitioners”
“Alternative Health Care Practitioners” are pretty much anyone who wants to hang out a shingle and advertise himself as such. The Colorado legislature passed a law in 2013, which I call “the Quack Full Employment Act,” allowing folks to do exactly that, but put the same sort of restrictions on their treating children as it did on naturopaths. (Not very flattering for the naturopaths, if you think about it.) A bill tried to remove those restrictions, but failed.
All in all, the 2013-2014 legislative session (or sessions, depending on where you live) were a bust for chiropractors, naturopaths, acupuncturists and assorted other practitioners of pseudo-medicine. Let’s keep it that way for 2015-2016. We’ll be following CAM bills over at SFSBM. These are target-rich subjects, making it inevitable that SBM bloggers will “review” them from time to time as well.
Even better, we at SFSBM aren’t stopping with the Maryland naturopaths in our efforts to give science and consumers a voice when CAM practitioners go for licensing or try to expand their scope of practice. You can help by keeping up with what is going on in your state using the vast amount of information on SFSBM and SBM to educate your legislators. Looks like they could use some help.
A newly-published review of neuroscience research looking at the predictive value of functional and anatomical imaging raises interesting questions about the role of such studies in learning, psychiatric treatment, and even the treatment of criminals. “Prediction as a Humanitarian and Pragmatic Contribution from Human Cognitive Neuroscience” by Gabrieli, Ghosh, and Whitfield-Gabrieli and published in Neuron, does a thorough job of explaining the current state of the research and pointing to where future research is needed.
The basic idea is to use noninvasive imaging to look at the structure or function of the brain as a way of predicting future behavior, and then using those predictions to help guide treatment and education interventions, and perhaps decisions regarding parole or further treatment of criminal behavior. This concept raises many issues, including the technology being used, the state of the research, the ultimate potential for this line of research, and ethical considerations.
The major question underlying this entire endeavor is, to what extent is brain anatomy and function destiny?The technology
There are two basic ways to look at the brain to determine its functional potential with regard to specific tasks (such as reading, impulse control, tendency toward depression, etc.). The first is to look at anatomy independent of any current task being performed. Essentially this approach uses MRI scanning to measure the thickness or overall size of gray matter regions or of white matter tracks. If, for example, the “cable” that connects the two main language processing areas (called the arcuate fasciculus) is thicker, this may correlate with a greater ability to learn a new language or improve reading skills.
The advantage of this approach is that the technology is highly reliable and precise. This is simply a physical measurement.
The second approach is to look at brain activity during a specific task. There are several options for this approach: fMRI scanning (which measures blood flow) has a good spatial resolution but a poor temporal resolution, while looking at electrical or magnetic activity through EEG or MEG respectively has better temporal resolution, but worse spatial resolution.
These approaches have the advantage of looking at actual brain activity – seeing which parts of the brain are active during a specific task. They are currently less precise than purely anatomical techniques. They also have the added difficulty of being dependent on the subject performing the task that they are being instructed to perform (such as attempting to match words that rhyme). The researchers cannot know for sure how focused a subject is on the target task, or what mental method they are using to achieve the task.
Taken together, these techniques are relative new and powerful tools for looking at brain anatomy and function. They are detailed enough to be useful, but still have significant limitations.The research
The authors do an excellent job of reviewing the logic and methods behind research looking into using imaging technology to predict future outcomes (although their paper can get very technical at times). I will give a simplified summary here. Essentially, the first phase of such research is to look for correlations between some brain attribute and some outcome measure (such as reading skill or level of depression). Researchers can look for correlations within a group, between groups, or with change from baseline.
They correctly caution that correlations do not necessary equal causation. They further point out that such correlations are always overestimates, and that the more variability there is in the brain regions and markers being measured, the greater the ability to tease out some correlation (to find some apparent signal in the noise). Correlations therefore need to be confirmed by making predictions with a fresh data set.
They outline various statistical methods for creating a model based on correlations and then testing the model by using it to make predictions about a different data set.
The bulk of the paper then reviews existing research in various areas. Overall existing research is mostly preliminary. Most studies are small in size and look mainly at correlations. Few have done the follow up of testing their models with predictions using fresh data. Therefore, while this may be an exciting area of research, the published studies have not yet matured to the point where we can make practical use of the results.
What the current research does show is that there is a modest but real correlation between brain imaging and various cognitive outcomes. The data is most robust and convincing with respect to language. This makes sense, since there are brain structures dedicated to language processing, and the robustness of this processing is likely to correlate to language ability.
Another area where the authors point out the research is fairly solid is depression, for example looking at brain responses to depressed faces and outcomes of treatment for depression. I also assess the research looking at impulse control and the frontal lobe structures that correlate with such control as being fairly solid.
However, even in these areas where there is a clear correlation, the amount of predictive value tends to be fairly modest. In many of the studies reviewed, positive imaging predicts only 20% or so of later variability. In a study of reading outcomes, traditional ability measures predicted 65% of later outcome, while brain imaging predicted 57%. However, when the two types of information were combined, predictive value increased to 81%.Future research and applications
The authors correctly point out that if this line of research is to be useful clinically then the research needs to progress to much larger studies which look at the predictive value of models based on correlations. In addition, we need to get more and more detailed in terms of correlating specific brain structures or activity and specific clinical outcomes.
I do wonder, however, what the ultimate limit will be for this line of research. The brain is a complex system, with many different tasks and abilities interacting in a complex way to yield an end result. There may be some low-hanging fruit to pick, such as with reading and language skill. With such tasks there may be a tight correlation between the organization of the brain and ultimate ability. For other more complex outcomes, such as criminality, there may be significant limits on how predictive such approaches can be.
It may be necessary to take the research farther still – looking at many different parts of the brain and then computer modeling their interaction. We may still get to the limits predicted by chaos theory, however. We can’t predict weather accurately beyond 5 days or so, and we may not be able to predict human behavior and outcomes beyond a certain limit also.
In addition there is the issue of the relative contribution of brain anatomy compared to plasticity (the ability of the brain to change its wiring), environment and learning. We are likely only looking at potential by looking at the brain. This of course will have a statistical predictive value, but this does not mean that brain anatomy is destiny for an individual. If we can’t apply this data to an individual (only statistically to groups) then perhaps the vision of the authors will never be fully realized.
This issue blends into the ethics of looking at the brain in order to determine future outcomes. Should a criminal be denied parole because his brain imaging shows relatively-low impulse control, which predicts a higher probability of recidivism?
Where this type of information can be useful (and the authors do point this out) is adding predictive information to help guide treatment decision in certain psychiatric disorder and education interventions. If we can identify at an early age those students who will have difficulty with language and reading, then they can be given greater resources in that area to help them keep up with their peers. This is already being done, using standard testing, but the evidence suggests brain imaging might add to the predictive power of such testing.
In the clinical setting brain imaging may help predict who will respond better to one type of drug over another, or to cognitive behavior therapy. Medical interventions are largely based on statistical data with large groups, and this approach would be no different.Conclusion
I largely agree with the authors that the new wave of brain anatomical and function imaging has brought with it a new age of understanding the brain. I also agree that there is tremendous potential to use this type of imaging to guide interventions for education and psychiatry. Applications to criminal justice are more complex and fraught with ethical considerations.
We are, however, still years away from practical applications. We need, as the authors suggest, to do large studies of predictive value. But then we also need, in my opinion, to do clinical outcomes research – looking at the net outcomes from employing this type of data in real world situations.
One fear that I have (and the authors also point this out) is that the allure of such data will give it a mystique that goes beyond its real world applicability. If people think we can peer into someone’s brain and predict their future, there would be the strong temptation to treat brain scans as if they were destiny, and short circuit more thorough and nuanced methods for evaluating individuals and optimizing interventions.
In the end I think that this approach will be one more tool in our toolbox, and it can be a powerful tool. Such data will still need to be used thoughtfully, with a full appreciation of its limitations.
At the most recent meeting of the Indian Science Congress Association, Captain Anand J Bodas, apparently under the aegis of Mumbai University, gave a lecture in which he claimed that airplanes existed in India 7,000 years ago, that they were able to fly to different continents, and even to different planets.
These claims are obvious nonsense (although I will link to a summarize resources which painstakingly demonstrate this). What is more interesting is that such a talk was able to infiltrate what is apparently a science conference. This is a disturbing phenomenon, all too common, in which rank pseudoscience is able to work its way into the domain of respected science.
Universities, conferences, TED talks, journals, and scientific organizations have a responsibility, in my opinion, to maintain minimum standards for any material they present. Sometimes they try to evade responsibility by claiming that allowing the use of their venue or medium is not an endorsement, but that is patently not true. The public perceives it as such, the pseudoscientists exploit it as an endorsement, and therefore it is, de facto, an endorsement.
Given the proliferation of information (which is a good thing) it is all the more important for professional organizations and institutions to provide a guide to the public as to which sources are legitimate and reliable. The cranks want to blur the lines because they want the imprimatur of legitimacy.
There is another element here and that is cultural or nationalistic pride. This is also a common phenomenon – scientists engaging in pseudoscience in order to bolster the esteem of their culture, by claiming ancient origins, historical accomplishments, or the legitimacy of their cultural beliefs. Perhaps this motivation causes scientists to be more tolerant of dubious methods than they otherwise would be. Of course, the potential conflict of interest should motivate them to be more skeptical, not less.
Let’s get to the ancient Indian planes. Fortunately I don’t have to spend too much time debunking the specifics of this claim, because scholars have already done so, back in 1974 – over 40 years ago. As an aside, this is an excellent example of why scholars at times need to pay attention to pseudoscience and debunk it. Their work can then serve as a resource when the pseudoscience pops up again, as they always seem to do.
The source of this particular myth comes from two books published in the 1950s in which the authors interpret ancient writings at face value while at the same time imaginatively interpreting the text. Many cultures imagined building machines that would fly like birds. Just because someone wrote about it doesn’t mean such devices existed.
As you can see from the image above, the described machines could never have flown. They are fanciful and lack any knowledge of aerodynamics, or any plausible mechanism for lift, propulsion, or control. There is no description in the text of the underlying knowledge that would be necessary to design and build such machines. They simply describe machines that could not possibly fly, lacking in sufficient detail, and what details they do give are contradictory and nonsensical.
If you are interested in the gory details, then read the original report linked to above.
The story here is that a bit of obvious pseudoscience, debunked 40 years ago, worked its way into a prestigious science conference, over the objections of some members. It is reported that:
An online petition by a scientist at the NASA research centre had demanded that the scheduled lecture be cancelled as it mixes mythology with science.
The purpose of the organization is to promote science in India. Allowing such nonsense into their conference has diluted that mission, and distracted from the conference.
In a recent “Perspective” article in The New England Journal of Medicine, three physicians (Drs. Cox, Borio, and Temple) make a strong case for not letting the rush to save Ebola patients tempt us to deviate from good science and skip the randomized controlled trial (RCT). Their arguments cut to the essence of the scientific approach to medicine, and they deserve careful consideration.
Ebola is uniquely scary
Ebola is the kind of threat that really gets our attention. The virus was first identified in 1976, and prior to 2013 there were several small outbreaks in Africa with death rates as high as 90%. This time the death rates are lower, but the numbers are much greater. It has spread to several African countries, and a few cases have even reached the US and Europe due to infected travellers and health care workers. We face a risk that Ebola may become endemic, smoldering along as a constant presence in Africa.
There is no known effective treatment. Fear of Ebola has sparked bizarre conspiracy theories and claims of “natural” cures and prevention kits from homeopaths, alternative medicine advocates like Mercola, and purveyors of remedies like colloidal silver and essential oils. These have been covered on SBM here, here, and here.
The current approach consists of early identification, isolation, rigorous infection control protocols with space-suit-like personal protective equipment for health care providers, supportive care with intravenous fluids, and conventional treatments for symptoms and complications. The death rate is lower where good medical care is readily available. As of 31 December 2014, the WHO announced there had been 20,206 reported cases with 7905 reported deaths, for an overall fatality rate of 39%. But the reported case fatality rate in the three intense transmission countries among all cases for whom a definitive outcome is known is 71%, and the numbers are uncertain because under-reporting continues to be a challenge.
A number of experimental treatments have been tried or are being considered. Several patients have been given serum transfusions from recovered patients to passively supply them with antibodies to the virus. ZMapp, a combination of monoclonal antibodies, has been used to treat 7 individuals; some of them recovered, some did not. Several anti-viral drugs are under development, and certain selective estrogen receptor molecules and ion channel blockers have also shown promise in vitro.
In the face of such a deadly threat, we can’t afford to sit back and wait for the results of randomized controlled trials (RCTs) published in peer-reviewed journals. We are tempted to try any reasonable-sounding experimental treatment before the results of clinical trials are in. Some of these experimental treatments might be unsafe and ineffective, but we know Ebola is definitely unsafe and deadly. The doctors who gave their critically ill patients serum transfusions or ZMapp did exactly what most of us would have done in the same circumstances. But was it really the best thing to do?
The need for RCTs
If we give patients ZMapp without a control group and some of them recover, how are we to know whether ZMapp contributed to their recovery? Some have argued that we wouldn’t want to deny treatment to a control group, and that we can compare the recovery rate with ZMapp to the historical recovery rate without it. That approach is particularly problematic with Ebola, since the historical recovery rate is so variable and so dependent on differences in supportive treatment and other confounding factors. As Cox, et al. point out, “the historical case fatality rates are irrelevant if current study patients receive better supportive care.”
They argue that allowing patients access to investigational drugs outside of properly designed randomized controlled trials can have tragic consequences. Using no controls or only historical controls might lead to rejection of treatments that have real but modest benefits, or it might lead to widespread adoption of a treatment that is useless or even harmful. And there are ethical considerations. Limited supplies of investigational drugs have been given to favored Western health care workers instead of being equitably distributed to all candidates.
RCTs tend to be slow and cumbersome, but there are ways to streamline the process. They explain,
…advances in trial design can and should be incorporated into Ebola RCTs. For example, such trials should include ongoing monitoring of results (e.g., group-sequential designs), adaptive elements, and other trial efficiencies to reduce the time required to identify an effective treatment, particularly a very effective treatment. If one investigational drug clearly shows benefit, trials should incorporate it into the new standard of care for all treatment groups thereafter. Then a regimen adding a different investigational therapy to the new standard of care could be compared with the new standard of care alone. If multiple investigational drugs are simultaneously available for clinical testing, an RCT could include more than one drug and a shared control group. Trials could be designed to assess effects on survival (recovery from disease) as the most important and measurable end point…
Scientists at the National Institutes of Health, in collaboration with the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Defense, and clinicians caring for patients with EVD in the United States, are leading efforts to develop and implement such trials.
This is a principle that applies to all new treatments in mainstream medicine as well as to the treatments offered by so-called “alternative” medicine and “integrative” medicine. A single anecdote about a single patient tells us nothing, and an uncontrolled study is little better than a collection of anecdotes or testimonials. Anything can seem to work in an uncontrolled study; we have seen many examples of studies with apparently positive results even for things as ridiculous as homeopathy, therapeutic touch, and retroactive prayer.
It has been argued that patients should have ready access to untested and experimental treatments, and that they have the right to try anything they want, especially when their life is at stake and there is no treatment available that has been tested and proven effective. In some cases, trying an untested treatment might very well help the individual patient; but if the treatment is really effective, providing it outside of controlled trials tends only to slow the progress of science and delay the day when that treatment will be proven effective and added to the armamentarium of conventional medicine so that it can benefit all patients. We need to determine whether a treatment works or doesn’t work, and there is only one way to do that: using scientific methodology.
From bloodletting for fevers to internal mammary artery ligation surgery for heart disease, the history of medicine is littered with treatments that were believed to work until they were discredited by rigorously controlled studies. Randomized controlled trials are the most reliable way to determine whether any new treatment is safe and effective. It is tempting to bypass them and offer experimental treatments to desperately ill Ebola patients outside of a properly designed RCT. We would be wise to resist that temptation and to insist on enrolling patients in a proper clinical study.
Please don’t misunderstand. I am not saying we shouldn’t use untested treatments in a last-resort situation. I am not saying that access to experimental treatments should be restricted. I am only saying that when experimental treatments are used, they should be used as part of a well-designed clinical trial so that we can learn something from the experience. I recognize that enrollment in a clinical trial is not always feasible, but it is a worthy goal. As a society, we should aspire to take whatever actions are necessary to develop and fund such trials for as many patients as possible.
This is one of those glass-half-full / glass-half-empty news items. Different headlines reporting on the same study present the results in opposite ways. The BBC, for example, writes, “Life choices ‘behind more than four in 10 cancers.’” Meanwhile the press release from Johns Hopkins states, “Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows.”
The Hopkins headline is more accurate. The BBC headline is not just focusing on life choices vs bad luck, it actually gets the data wrong.
What the researchers did was look at the replication rate of stem cells in different tissue types (they did not include breast cancer and prostate cancer as they could not find published replication rates). They then compared differences in these rates to differences in adult cancer rates in the same tissues. For example, colon cancer is more common than cancer of the small intestine, and colon cells replicate more frequently than small intestine tissue. (In mice, this is reversed, but the correlation holds.)
All cancers, the authors emphasize, are a result of random mutations, lifestyle factors, and inherited genes. The latter two can affect the rate of random mutations and perhaps also the probability of cancerous cells being destroyed by the immune system vs growing into a cancer. The mutations result in cancer by altering the cell’s growing characteristic, allowing them to grow without limit. Normally cells posses mechanisms that keep them from growing out of control, and mutations may disable one or more of those mechanisms.
The authors hypothesize that if getting unlucky random mutations were the sole cause of cancer, then 100% of the difference in cancer rates among various tissue types could be explained by variation in their stem cell division rates. Statistically this means there would be a complete correlation between these two variables (a correlation of 1.0). They found a correlation of 0.804. This translates into 65% of the difference in cancer rates being explainable by differences in stem cell mutation rates.
The correlation was not the same for all tissue types. Some tissues had a very tight correlation, meaning cancers of those tissues are almost entirely due to random mutations. Other tissue types had a low correlation, the obvious one being lung cancer, which is largely caused by smoking. Of the 31 tissue types they looked at, 22 had a strong correlation between cancer rates and stem cell division rates. Those that did not were basal cell skin cancer (sun exposure is a major risk factor), head and neck and lung cancer (smoking is a risk factor), hepatocellular (liver) cancer, thyroid cancer, and several types of colon cancer.
The study, however, did not look directly at the contributions of inherited genetics and lifestyle factors, which is why the BBC headline is wrong. They assumed that not bad luck equaled lifestyle, but it equaled lifestyle plus genetics, which was not separated by this study.
The two cancer types not included, breast and prostate, are not largely lifestyle cancers, and so once they are included I suspect the percentage of overall cancers that are due to random mutations will increase.
This is an interesting study and it will be interesting to look at replications and other methods, if they are available, of making the same sort of estimation. What this study suggests is that at least 2/3 of all all cancers are due to random mutations – bad luck. The figure may be higher once breast and prostate cancers are included. Of the remaining third it is not clear how much is due to inherited genes vs lifestyle factors.
The logic of the study is sound, in my opinion. The authors assume that lifestyle and genetic factors affect the risk of tissue specific cancers, but not cancer in general. This study would miss, however, lifestyle or genetic factors that affected the risk of all cancers (regardless of tissue type) equally. One might argue, therefore, that it overestimates the role of random mutations, but that is only if you accept that there are universal risk factors out there.
Of course we want to focus on the lifestyle factors, because that is the one thing we can control. If you avoid smoking, avoid excess sun exposure, and have a generally healthful diet, you are probably covering the vast majority of lifestyle factors that affect cancer risk. That is some comfort.
But still the majority of cancer risk is something we cannot do anything about (our own genetics, and just being alive). The researchers emphasize from this that we therefore need to focus our attention on early detection and treatment of cancer.
The good news is we are making progress. The latest figures show that death from cancer has declined by 22% since its peak in 1991. This translates into 1.5 million cancer deaths avoided if rates had remained at their peak level.
Also, 27% of cancer deaths are due to lung cancer, which is strongly linked to smoking. Therefore, if you avoid smoking then you are avoiding most of the lifestyle associated cancer risk. Breast, colon, and prostate are also among the most common cancers, with these four representing half of all cancers. Breast cancer deaths have decreased by 35% and colon and prostate by 47%.
Hopefully these trends will continue, with improved detection and treatment of various types of cancer. Meanwhile, if you want to reduce your own risk, then don’t smoke. Avoiding excess sun is also important, but not nearly as large of a risk factor. There are many reasons to have a generally healthy diet – well rounded with plenty of plants. Just as important, however, if to follow screening guidelines. See your doctor and follow their recommendations.
One of the more difficult conversations to have with a patient as a cancer doctor occurs when a patient, recently informed of her diagnosis of, for example, breast cancer, asks me, “Why did I get this? What caused it?” What almost inevitably follows is an uncomfortable conversation in which explanations of the multiple known causes of breast cancer do not satisfy the patient. The reason, of course, is because when a patient asks, “What caused it?” she doesn’t mean what causes breast cancer in general or in statistical terms. Rather, she means, what caused my breast cancer? It’s a question that can only occasionally be answered. For instance, if it’s lung cancer and the patient is a smoker, then it was almost certainly smoking that caused the cancer, because lung cancer is a relatively rare cancer in the absence of smoking. In the case of breast cancer, contrary to the prevailing belief that leads women with breast cancer to be puzzled about how they could get it when there’s “no cancer” in their families, only around 5-10% of cases have a familial or genetic component. That means that around 90% of breast cancers are what we call “sporadic,” which means that we can’t identify a specific cause. Or, as I like to say, “We just don’t know.” Worse, in the case of breast cancer, the environmental factors we know about appear to contribute at best, modestly, to the risk of cancer. (More on this later.)
Understandably, patients hate hearing, “We just don’t know,” some vague handwaving about genes, and that there is nothing that we know of that they did that caused their cancer. People—including oncologists—really don’t like the concept of “sporadic” cancer, mainly because humans crave explanation. The default assumption is that everything must happen for a reason and there must be a cause for every disease or cancer. Perhaps the most ridiculously emphatic statement of this that I’ve encountered thus far comes from (who else?) über-quack Mike Adams when he heaped contempt on the idea of sporadic disease as “spontaneous disease.” He did this in the context of a story describing how, after Dr. Mehmet Oz had followed recommended care and undergone screening colonoscopy to look for polyps, he was shocked that he actually had some. This led Adams, in his usual inimitable fashion, to construct a straw man so massive that it could be seen from space when he set it on fire, declaring that “colon polyps, in other words, appear without any cause!” and that “mainstream medicine…believes in the theory of ‘spontaneous disease’ that ‘strikes’ people at random.”
On the other hand, there is a lot of randomness in disease, not just cancer, as hard as it is for Mike Adams, or anyone to accept. Just because there is a varying amount of randomness in who gets a disease does not mean that mainstream medicine claims there is no cause to these diseases. Rather, for diseases like cancer, it’s a stochastic process, meaning that chance can play a role—sometimes a big role—in determining who gets sick. Indeed, just last week there was more evidence supporting this idea published in Science. Unfortunately, much of the mainstream press coverage presented the message of the paper a bit too simplistically. Even more unfortunately, it was the authors who encouraged this, as did the Johns Hopkins University press release about the study, which was entitled, Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows. Yes, I groaned when I read these titles.
Other headlines followed Hopkins’ lead:
I groaned. Then it was once more unto the breach.Is cancer mostly “bad luck”?
The paper itself, by Cristian Tomasetti, a biostatistician interested in cancer evolution, genomics, and stem cell dynamics, and Bert Vogelstein, the latter of whom is a giant in cancer research, the man who pioneered the concept of tumor suppressor genes, validated p53 (TP53) as a tumor suppressor gene, discovered (with collaborators) the APC tumor suppressor gene, and whose team developed a major model explaining the progression of colorectal cancer from normal epithelium to polyp to dysplastic polyp to in situ cancer to cancer, is entitled Variation in cancer risk among tissues can be explained by the number of stem cell divisions. This, of course, is a different message than what is being promoted in the Hopkins press release and all the news stories that flowed from that. It is, however, a fascinating paper, although certainly not without issues, and it does support the idea that a large percentage of cancers tend to be due to mutations that occur during DNA replication during cell division.
The authors start out by noting:
Extreme variation in cancer incidence across different tissues is well known; for example, the lifetime risk of being diagnosed with cancer is 6.9% for lung, 1.08% for thyroid, 0.6% for brain and the rest of the nervous system, 0.003% for pelvic bone and 0.00072% for laryngeal cartilage (1–3). Some of these differences are associated with well-known risk factors such as smoking, alcohol use, ultraviolet light, or human papilloma virus (HPV) (4, 5), but this applies only to specific populations exposed to potent mutagens or viruses. And such exposures cannot explain why cancer risk in tissues within the alimentary tract can differ by as much as a factor of 24 [esophagus (0.51%), large intestine (4.82%), small intestine (0.20%), and stomach (0.86%)] (3). Moreover, cancers of the small intestinal epithelium are three times less common than brain tumors (3), even though small intestinal epithelial cells are exposed to much higher levels of environmental mutagens than are cells within the brain, which are protected by the blood-brain barrier.
Another well-studied contributor to cancer is inherited genetic variation. However, only 5 to 10% of cancers have a heritable component (6–8), and even when hereditary factors in predisposed individuals can be identified, the way in which these factors contribute to differences in cancer incidences among different organs is obscure.
So this is what we know about cancer. Its incidence varies tremendously among tissues in a way that can’t be explained by environmental exposure or heredity. I might quibble with the authors’ not discussing lung cancer more as a major exception to this tendency, given that nearly all lung cancer is caused by tobacco smoking, but overall for most other cancers this is basically accurate. Given the inadequacy of environmental factors and inherited genetic mutations as explanations for how cancers arise, the authors then tell the reader how this led them to look at what they call a “third factor”: the stochastic effects associated with the lifetime number of stem cell divisions within each tissue. The first thing that struck me as I read this paper is that this is not a new or radical idea. Far from it! It’s long been known that tissues with cell types that undergo rapid division over a life time tend to be more susceptible to developing cancer; e.g., the epithelial cells of the colon, which are prone to cancer, compared to cancers arising in the brain or in muscle, where cells divide much less. The reason, it’s been hypothesized, is that more rapid cell division leads to more errors in DNA replication, which leads to more mutations. However, there are glaring exceptions, such as small intestine, whose epithelial cells replicate rapidly and continuously throughout the human lifespan. Yet small bowel cancer is rare.
The question most readers have, probably, is why Tomasetti and Vogelstein wanted to concentrate on stem cells. The reason is simple and fairly obvious. Most cells are fully or partially differentiated, and the population of cells responsible in most tissues for the development and maintenance of the tissue and its architecture as well as for replacing cells that are lost is in most organs a relatively small proportion of the cells there. As is pointed out in the paper, until recently, the nature, number, and hierarchical division patterns of various stem cells were not well characterized. In any case, the hypothesis being tested in this paper relies on three key concepts: (1) that cancer is mostly the result of acquired genetic and epigenetic changes; (2) genetic changes occur primarily by chance during DNA replication; and (3) that the endogenous mutation rate of all human cell types appears to be very similar. These concepts, taken together, predict that the number of cell divisions among stem cells in each organ during a lifetime should correlate strongly with the lifetime risk of cancer in that organ. To test this prediction, Tomasetti and Vogelstein set out to estimate the lifetime number of stem cell divisions in each organ and determine if it correlates with cancer risk in that organ.
So Tomasetti and Vogelstein reviewed the current literature, identifying 31 tissue types in which stem cells had been quantitatively assessed. They then plotted the total number of stem cell divisions during the average human lifespan on the X-axis and the the lifetime risk for cancer as recorded in the Surveillance, Epidemiology, and End Results (SEER) database in that organ on the Y-axis. Here’s the end result in Figure 1:
As you can see, there is a striking highly positive correlation on a log-scale graph. As noted by the authors, this correlation extended across five orders of magnitude and encompassed cancers with tremendous differences in prevalence. The authors note:
No other environmental or inherited factors are known to be correlated in this way across tumor types. Moreover, these correlations were extremely robust; when the parameters used to construct Fig. 1 were varied over a broad range of plausible values, the tight correlation remained intact…
A linear correlation equal to 0.804 suggests that 65% (39% to 81%; 95% CI) of the differences in cancer risk among different tissues can be explained by the total number of stem cell divisions in those tissues. Thus, the stochastic effects of DNA replication appear to be the major contributor to cancer in humans.
It seems pretty bullet-proof, right? Well, maybe. Maybe not. As was pointed out by Paul Knoepfler, the single most difficult issue in this analysis is how to accurately and consistently calculate reliable estimates of the number of lifetime stem cell divisions in a series of diverse tissues. This is far from a trivial matter, or, as Dr. Knoepfler describes it, “extremely difficult and it’s not difficult to imagine such calculations being off by one or more orders of magnitude.” For instance, take a look at this description in the supplemental data how stem cell divisions were calculated for adenocarcinomas and squamous cell carcinomas of the esophagus (which I’ll quote because I realize that most of you don’t have access to the paper itself):
The lifetime incidence of cancer of the esophagus is ~0.51% (3). The vast majority of these cancers are either adenocarcinomas or squamous cell carcinomas, and the ratio of these two types has changed considerably in the last few decades. Currently, ~38% of esophageal cancers are squamous cell carcinomas (66, 67). The lifetime incidence of esophageal squamous cell carcinoma is therefore 0.0051·0.38 = 0.001938. The esophagus is 18 to 26 cm long and 2 to 3 cm in diameter (68), resulting in an average surface area of ~172.79 cm2. The area of a squamous cell in the basal layer is ~80μm2 (69). The fraction of stem cells in the basal layer has been estimated to be 0.4% of the total basal layer cells (70), so there are a total of ~2.16·108 basal cells and 8.64·105 stem cells in the basal layer. As the normal mucosal epithelium is ~10-20 layers thick, the total number of epithelial cells in the esophagus is estimated to be ~2.16·108 ·15= 3.24·109. Cells have been estimated to turn over ~ every 21 days (71, 72).
As you can see, multiple assumptions had to be made for each parameter, and then these parameters are multiplied together to estimate the total lifetime number of stem cell divisions. To be fair, one thing Knoepfler didn’t mention is that there was a statistical analysis done to test the robustness of the correlation in which the estimates of total stem cell divisions was allowed to vary by 100-fold in either direction, but even so, there are a number of other issues. For instance, not all cancers originate with stem cells, and some organs have more than one type of stem cell population. Yet the paper seemed to treat stem cells as one population for each organ. Still, as a first approximation, it’s not unreasonable to do it this way.
In addition, to try to tease out which tissues are more prone to cancer than their stem cell replication totals would suggest, Tomasetti and Vogelstein calculated what they call an “extra risk score” (ERS), defining it as the product of the lifetime risk and the total number of stem cell divisions (in log10). Machine learning methods were then used to classify tumors based only on this score. The details are a bit much, even for me, but the bottom line is that the ERS is meant to be a measure of how well that particular tumor type “fits the model.” More specifically:
If the ERS for a tissue type is high—that is, if there is a high cancer risk of that tissue type relative to its number of stem cell divisions—then one would expect that environmental or inherited factors would play a relatively more important role in that cancer’s risk (see the supplementary materials for a detailed explanation). It was therefore notable that the tumors with relatively high ERS were those with known links to specific environmental or hereditary risk factors.
The authors referred to tumors with high ERS values as “D-tumors” (for “deterministic,” meaning deterministic factors such as environmental mutagens or hereditary predispositions strongly affect their risk) and tumors with low ERS values as “R-tumors” (for “replicative”) in which stochastic factors, most likely errors during DNA replication as stem cells divide, most strongly affect risk. Not surprisingly, cancers that came up as D-tumors with high ERS scores included colorectal cancer related to familial adenomatous polyposis (FAP), which is due to a mutation in a tumor suppressor gene (APC) and whose most severe form results in a 90+% risk of colorectal cancer by age 50, and to Lynch syndrome (HNPCC or hereditary nonpolyposis colorectal cancer), which is due to an autosomal dominant inherited mutation that produces a high risk of colorectal cancer, as well as endometrial cancer, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Lynch syndrome is due to defects in DNA mismatch repair, which lead to—you guessed it—more mistakes during DNA replication, leading to more mutations. People with Lynch syndrome have an 80% lifetime risk of colorectal cancer. Indeed, in general, so high is the risk of colorectal cancer in people with FAP or HNPCC that close monitoring with regular colonoscopies is always recommended, and prophylactic surgery to reduce the risk of cancer by eliminating the tissue at risk is frequently recommended. The recommended operation is usually total proctocolectomy (removal of the entire colon and rectum) as young adults, although because there are less aggressive variants of FAP sometimes close monitoring is appropriate for FAP.
One little nit I have to pick with this graph is that the lung cancer cases are divided into smokers and non-smokers. Again, lung cancer, which is such a leading cause of preventable cancer (with the authors noting that smoking increases lung cancer risk 23-fold in men and 13-fold in women, for an overall 18-fold increase in risk), is a special case, but that doesn’t justify dividing the cases of lung cancer into those related to smoking and those unrelated to smoking. Doing so smacks of trying to downplay one case of environmental factors being very important. After all, there are other cancers whose incidence is very much influenced by smoking, including esophageal cancer, head and neck squamous cell cancers, and pancreatic cancer, but no such effort was made to divide these tumors into smoking-induced and not smoking-induced. This lapse is curious and not explained in the paper at all. Either all the strongly smoking-induced cancers or none of them should have been divided into groups based on smoking.
Another issue is that most of the “D-tumors,” the ones known to have definite genetic or environmental causes that fell out were tumors caused by genetics. Of tumors known to have a strong environmental component, only smoking-induced lung cancer, basal cell carcinoma (due to sun exposure), and thyroid cancer (follicular or papillary types, known to be significantly due to radiation exposure) showed up in the D-tumors group. This made me wonder if Tomasetti and Vogelstein’s model was sensitive enough to pick up tumors that have a significant environmental component, given that environmental influences tend not to produce cancer risks as high as seen in people harboring genes for inherited cancers, for which mutant gene carriers can have up to a 90% lifetime risk of cancer when they have a particularly nasty genetic predisposition.
There are other problems. The first is a rather glaring anomaly. Oddly, malignant melanoma, which is known to be strongly associated with sun exposure, showed up as an “R-tumor,” and no discussion was offered to explain why this might have happened. Again, this brings into question the sensitivity of the model. Next, two major cancers, breast and prostate cancer, were not included in the analysis because Tomasetti and Vogelstein could not find good estimates in the literature for stem cell proliferation rates for these cancers. Given that these are two of the “big three” cancers with the highest incidence in the US (breast, prostate, and lung cancers), this omission presents a problem for generalizability. Overall, I wonder why Tomasetti and Vogelstein didn’t just show the first graph, which pretty much gives us all the information we need. The second analysis involved a transformation of the data whose rationale is not clear and even questionable, and that is not particularly informative. I understand why they did it, but I think it weakens the paper.
As has been pointed out elsewhere by Bob O’Hara and Grrlscientist, what is being represented as “bad luck” might or might not be that. What Tomasetti and Vogelstein’s calculations show is that, in their model, 65% of the variability in cancer incidence between tissues, which, they argue, is not the same thing as what proportion of cancer is due to “bad luck.” What they are, in fact, describing is the stochastic component related to differences in stem cell proliferation, but “bad luck” is pithier and easier to understand. Therein, I suspect, lays their problem. It would have been a lot less interesting to the press to say that 65% of the variation in incidence between 31 cancers is explained by variations in lifetime stem cell proliferation in those tissues.
Perhaps the most reassuring thing about this paper, oddly enough, is that, even after their having estimated the variability in incidence explained by stem cell proliferation and determined that 65% of tumors risk is correlated with stem cell proliferation and thus the accumulation of errors in replication, Tomasetti and Vogelstein’s estimate isn’t too far off from what we already know, as you will see. That’s part of the reason why I tend consider objections to the paper by bloggers like Bob O’Hara and GrrlScientist and The Stats Guy, to be at least partially missing the point, at least from my perspective as a cancer biologist and clinician, in that they tend to focus on semantics (namely the use of the term “bad luck”) and purely statistical issues rather than considering these findings in context of what we already know about cancer biology. PZ Myers noted this problem before I did (damn this publication schedule in which I had to wait until Monday to post this!), but, for example, one of O’Hara and GrrlScientist’s key objections is:
So, what proportion of cancers are due to bad luck? Unfortunately it’s difficult to tell from the paper. The figure from the paper is on the log scale, and if we extrapolate the model to zero (no cell divisions), we’d see it assumes there is no risk of cancer.
To which PZ PZ replied:
That’s what we’d expect if the magnitude of Mystery Factor X was 0, and the baseline rate of somatic errors leading to cancer was set by the replication error rate.
I’ll also add that this is not at all unreasonable of an assumption as a first approximation for such a model. After all, without cell division there can’t be cancer, regardless of the source of cancer-causing mutations, random during DNA replication, epigenetic changes, or other sources. If the cells don’t divide, even mutations caused by something other than errors in DNA replication won’t be passed on and can’t accumulate to result in carcinogenesis. In any case, what Tomasetti and Vogelstein were correlating was the variability in cancer incidence that could be attributed to variations in stem cell proliferation. That’s it. Absolute cancer risk for each tissue isn’t the issue, but rather variability in cancer risk and what contributes to it.In the ballpark
Let’s try to put Tomasetti and Vogelstein’s finding in context with respect to what we already know about cancer biology and epidemiology.
Any cancer biologist (like me), oncologist, or oncologic surgeon (like me) should know that we already have copious data for a large number of tumors that provide us with estimates of the relative effects of lifestyle and environment versus genetics versus randomness on risk. Part of what bothered me about this paper is that this was not adequately discussed. (Actually, it was hardly discussed at all, but then, it is a Science paper, and Science imposes ridiculously tight word limits on most articles.) While it is not really possible to prevent most inherited cancers short of relatively radical or invasive interventions (chemopreventative drugs like Tamoxifen for familial breast cancer, which reduces the relative risk by only around 50%, or surgery to remove the organ before cancer can develop, as is done to prevent familial breast and colorectal cancer), it is theoretically possible to prevent a lot of cancer. I say “theoretically” because actually implementing the interventions designed to prevent these cancers would often be incredibly difficult as a practical matter. Just consider how difficult it has been to get people to quit smoking and lose weight if you don’t believe me.
Perhaps my favorite quick and dirty (not to mention, reliable) reference guide to estimates of what percentage of different cancers are potentially preventable is published on the Cancer Research UK website. On a page entitled Statistics on preventable cancers, you can peruse the estimated relative contribution to various factors, such as smoking, alcohol consumption, diet, sunlight, radiation, and others, to a wide array of different human cancers. Not surprisingly, by far the most common cause of preventable cancer is tobacco, causing an estimate 86% of cases of lung cancer, 65% of cases of esophageal cancer and cancers of the oropharynx and head and neck, 37% of cases of bladder cancer, and 29% of cases of pancreatic cancer. Diet is estimated to contribute to 31% of bowel cancers, 46% of esophageal cancer, 51% of stomach cancers, and 56% of head and neck cancers. Alcohol contributes to several cancers, including breast, bowel, esophagus, oral cancers, and liver cancers, but the effects are much more modest. Sunlight contributes to 86% of cases of malignant melanoma, which, again, makes it very curious that melanoma showed up as an “R-tumor” in Tomasetti and Vogelstein’s analysis.
Overall, if you look at CRUK’s estimates of the percentage of cancers that are potentially preventable, you’ll find that, not surprisingly, it’s very high for smoking-related cancers like lung cancer (89%), esophageal cancer (75%), oral cancers (91%), pancreatic cancer (37%), and bladder cancer (42%). In contrast, it’s very low for cancers like non-Hodgkin’s lymphoma, prostate cancer, brain cancers, and myeloma. For the rest, it’s somewhere in between. Also included in the list are cancers caused by viral infections, such as cervical cancer, which can be prevented by preventing HPV infection.
One problem with much of the reporting of the study seems to be a misinterpretation of what the authors were getting at, which is stated near the end of the paper:
In formal terms, our analyses show only that there is some stochastic factor related to stem cell division that seems to play a major role in cancer risk. This situation is analogous to that of the classic studies of Nordling and of Armitage and Doll (10, 29). These investigators showed that the relationship between age and the incidence of cancer was exponential, suggesting that many cellular changes, or stages, were required for carcinogenesis. On the basis of research since that time, these events are now interpreted as somatic mutations. Similarly, we interpret the stochastic factor underlying the importance of stem cell divisions to be somatic mutations. This interpretation is buttressed by the large number of somatic mutations known to exist in cancer cells (14–16, 30).
In other words, even if taken at face value as reported in the media, Tomasetti and Vogelstein haven’t really demonstrated anything new. We’ve known for a long time that there is a strong stochastic (probabilistic) component to cancer development. The risk for some cancers appears to be mostly stochastic; the risk for other cancers is more strongly influenced by heredity; and the risk of other cancers, such as lung cancer, is more strongly influenced by environment. Some are influenced significantly by all three. These observations are, quite frankly, trivial. What Tomasetti and Vogelstein have done that’s different is to recast the stochastic component of cancer risk as not being due to just any old mutations in the cells in a tissue but rather to the accumulated mutations in stem cells, which is proportional to the total number of cell divisions. They then tried to estimate what percentage of cancers are primarily related to these stochastic factors and estimated that it’s around two thirds.
Now here’s the funny thing. If you interpret Vogelstein’s estimate the way it’s been represented in the press and by Vogelstein, as representing the percentage of cancers that are due primarily to “chance” and thus not related to environment and not potentially preventable (a not unreasonable interpretation, by the way), it turns out not to be such a bad first approximation at all. It’s actually not far off from what has been a fairly accepted estimate for quite a few years now, namely that between one third and one half of cancers are potentially preventable, implying that they are due to environmental causes that can be altered, such as smoking or diet. Given the level of uncertainty inherent in such estimates, even if you interpret Vogelstein and Tomasetti’s conclusion that two thirds of cancers are due to “bad luck,” their estimate of the percentage of cancers that are probably not preventable is definitely in the ballpark of commonly accepted estimates, albeit at the lower end. Does that mean they’re on to something in concluding that stem cell replication over one’s lifetime primarily determines the “stochastic” component of cancer risk for each organ? That remains to be seen, but their preliminary finding makes sense, both from the sense of producing a result that’s in the ballpark of what we already know based on epidemiology and being biologically plausible based on basic cancer biology.
There are two things that were probably responsible for the objections to this article. First, was its being presented as concluding that two thirds of cancers are due to “bad luck.” While I understand that Vogelstein probably wanted to simply things so that they would be comprehensible to everyone, he might have simplified them a bit too much in search of the pithy, memorable phrase. (He certainly succeeded at getting the study noticed!) Lost in the shuffle was a more nuanced discussion of what Vogelstein was getting at when he said:
“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.
“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,’ but the truth is that most of them simply had good luck,” adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.
That cancer is due to a combination of random probabilistic processes, environmental exposures, and heredity is a non-controversial statement. What is controversial are estimates of the relative contribution of environment, given that the percentage of cancers due to inherited cancer-causing mutations is known and low. Take the example of breast cancer, which is a cancer for which environmental and lifestyle contributions are not particularly high, with perhaps 27% of breast cancers being due primarily to environment (which includes diet and exercise, as well as hormone replacement therapy). The vast majority of those environmental contributions come from obesity and alcohol consumption, neither of which reaches the double digits, percentage-wise. Yet there are organizations that promote the idea that “chemicals” in our environment are a major cause of breast cancer. Unfortunately, about 5-10% of breast cancer is inherited, while perhaps up to 27% has a strong environmental component. That leaves around 60% of breast cancer (or, even using higher estimates, at least 50%) as falling into the “we don’t know” or “stochastic” category, with, sadly, nothing that we know of right now that can be done to prevent these cases, while the 10% of hereditary cases can only be prevented by aggressive means, such as chemoprevention or prophylactic surgery.
In other words, some of the objections to this paper seem to flow from a belief in inflated estimates of just what proportion of cancer is due to “environment” and therefore potentially preventable. It’s been suggested that cancer biologists might be too fast to blame unknown causes on “randomness,” the assumption being that not knowing something means that we will know it in the future and more prevention will be possible. The problem is that not knowing something doesn’t mean that there’s a realistic way of obtaining that missing knowledge or that even if we obtained that knowledge that we’d be able to do anything with it. Also, from a biology standpoint, we already know a lot about the stochastic nature of cancer formation, and within this framework Tomasetti and Vogelstein’s study “makes sense,” although it might have under- or overestimated the actual component due to errors in DNA replication in stem cells. Clearly the model needs refinement.
I have got to say that one question came to my mind instantly: who funded this cancer study? Sorry to be cynical, but when a study comes out that essentially clears all environmental factors from blame, I start to wonder if any of the funding came from, say, Monsanto. Whose interests might this study serve? Might we learn anything more if we follow the money? Maybe these questions have nothing to do with anything, but I think that they should be at least asked. We’ll certainly never find out the answers otherwise.
According to the acknowledgments, the work going into this paper, by the way, was supported by the The Virginia and D. K. Ludwig Fund for Cancer Research, The Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, and NIH grants P30-CA006973, R37-CA43460, RO1-CA57345, and P50-CA62924. No corporate funding there. It’s also a misstatement of the findings of the paper to say that it “essentially clears all environmental factors from blame. You can argue if it overestimates what percentage of cancer is related to variability in stem cell proliferation on some good statistical grounds, but a key finding of the paper is that at least one third of cancer incidence is not explained by this.
Unfortunately, Tomasetti and Vogelstein, did fall for another trap. Faced with their results, they demonstrated that they do probably do not understand the concept of overdiagnosis and overtreatment:
The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say. “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” says biomathematician Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. “We should focus more resources on finding ways to detect such cancers at early, curable stages,” he adds.
Unfortunately, as I and others have documented here time and time again, early diagnosis is a lot more complicated an issue than even most physicians—even oncologists and radiologists—realize. Overdiagnosis and overtreatment are real phenomena because detecting cancers at ever-earlier stages and ever-smaller sizes picks up cancers that would never threaten the life of the patient, but we have to treat them as though they would because we can’t (yet) predict which ones are safe to watch and which ones will progress. Early diagnosis does not lead inevitably to improved survival. We’ve discussed this issue again and again here with respect to mammography, PSA testing for prostate cancer, screening for cancer in general, and screening for other diseases. More screening is not necessarily better.
In actuality, if Tomasetti and Vogelstein are correct, the proper conclusion would be to try to reduce environmental exposures for cancers known to have a large environmental contribution. For tumors that are largely driven by accumulated errors in DNA replication in stem cells we need to work on understanding the pathways that drive their growth and progression in order to develop better targeted therapies, and to develop better surgical techniques to remove tumors for which extirpation is curative. Don’t get me wrong. Early detection can be useful, but it is very cancer type-specific and depends upon a tumor that progresses predictably from early pre-malignant stages and for which early intervention either prevents progression (as in removing polyps from the colon) or results in better outcome (which is true of several cancers, but not to the extent that we like to think, being confounded by lead time and length biases). Finally, because screening sensitivity and specificity depend strongly on the prevalence of the cancer being screened for, screening only makes sense for the most prevalent cancers, like breast, prostate, lung, and colorectal.
It’s understandable that humans crave explanation, particularly when it comes to causes of a group of diseases as frightening, deadly, and devastating as cancer. In fact, both PZ Myers and David Colquhoun have expressed puzzlement over why there is so much resistance is to the concept that random chance plays a major role in cancer development, with Colquhoun going so far as to liken it to ” the attitude of creationists to evolution.” Their puzzlement most likely derives from the fact that they are not clinicians and don’t have to deal with patients, particularly given that, presumably, they do have a pretty good idea why creationists object to attributing evolution to random chance acted on by natural selection and other forces.
Clinicians could easily have predicted that a finding consistent with the conclusion that, as a whole, probably significantly less than half of human cancers are due to environmental causes that can be altered in order to prevent them would not be a popular message. Humans beings don’t want to hear that cancer is an unfortunately unavoidable consequence of being made of cells that replicate their DNA imperfectly over the course of our entire lives. There’s an inherent hostility to any results that conclude anything other than that we can prevent most, if not all, cancers if only we understood enough about cancer and tried hard enough. Worse, in the alt med world, there’s a concept that we can basically prevent or cure anything through various means, most recently through the manipulation of epigenetics. Unfortunately, although risk can be reduced for many cancers in which environmental influences can increase the error rate in DNA replication significantly, the risk of cancer can never be completely eliminated. Fortunately, we have actually been making progress against cancer, with cancer death rates having fallen 22% since 1991, due to combined efforts involving smoking cessation (prevention), better detection, and better treatment. Better understanding what the contribution of stochastic processes and stem cell biology to carcinogenesis could potentially help us do even better.
Fad diets pop up on a regular basis. I believe that is because they are so easy to manufacture and there is a ready made market for them. Add to that the fact that it is difficult to lose weight. There is also a great deal of misinformation out there about diet and health, so the environment is very friendly to pop pseudoscience.
If you want to create your own fad diet, here is a handy formula. These things pretty much write themselves.
#1 – You need a catchy title, usually taking the form of “The blank Diet.” You can fill in the blank with almost anything. For example, a recent fad diet is called “the bulletproof diet.” This doesn’t say anything about the diet itself, it’s just a catchy phrase, a brand. You can fill in the blank with a title that does reflect the diet itself, but this is optional. Creating a catchy title is actually the most creative work you have to do in making a fad diet.
#2 – Make outrageous claims of success. The bigger the lie, the more people are inclined to think that it’s not a lie because no one would be that audacious. So just come up with a very impressive figure – a pound a day, 10 pounds a week, or whatever. In reality, on a healthy weight-loss diet people will lose about 1.5-2.5 pounds per week maximum, depending on their current weight, fat percentage, and other variables. Also, weight loss itself is not the ultimate goal, just a marker. People really want to reduce fat and build muscle. Following waist size is also a good measure, and perhaps better. Using the scale is helpful to make sure you are staying on track, however. Liberally use the world “miracle,” although admittedly Dr. Oz has tainted this word a bit by overusing it.
#3 – Testimonials. Personal stories, starting with your own, is the bedrock of fad diets. Don’t worry if there is absolutely no scientific evidence to support your claims – fad diets are not about evidence. They are about selling a narrative, one in which people struggled endlessly to lose weight, but then started the X diet and the weight just fell off. Testimonial can be very compelling, even though they are almost worthless as evidence. Actually, that is there advantage for you as a fad diet marketer, because you can find testimonials to support whatever claims you wish to make.
#4 – The Secret. Your fad diet has to have the secret or key to weight loss. Make this as compelling as possible, using language like, “unlocking the secret,” “hacking the body,” unleashing the genetic code,” or whatever. People know that sustained healthy weight loss takes hard work and that you have to change your habits and lifestyle. You won’t sell any books telling the truth. What people are looking for is the magical solution, a hidden secret that will allow them to lose weight without changing their habits, without diet and exercise. That is what you are selling.
#5 – Cherry pick the research. If you want to add a little optional bling to your website, you can link to research supporting your diet. Now, there won’t be any research that actually indicates your diet works, but don’t worry about that. You can cherry pick studies that appear to support your diet. For example, if your diet is low in carbohydrates, then link to studies showing some change in a petri dish with low carbs, or short term effects from a low carb diet, or any apparent advantage to lowering carbohydrates. You don’t even have to read the studies, just look for titles that seem impressive and seem to support your diet. Most people won’t click the links to read and understand the research anyway.
#6 – Sciencey Explanations. This part can be real fun – make up BS explanations for why your diet works. There are some good old standbys if you can’t think of anything original, so don’t worry. You can’t go wrong with toxins. Just mention toxins a lot, and say that your diet eliminates toxins. You don’t have to name specific toxins, or indicate how the toxins are eliminated, or any other details. Just mention that your diet eliminates toxins. Anti-inflammatory is another great buzz term. Your diet has anti-inflammatory effects, which enables the body to superburn fat. (You can just make up words like “superburn,” in fact it is encouraged.)
#7 – Demonize a food group. Every narrative needs a villain, and every fad diet needs a demonized food or food group. These are evil foods that make your body store fad and sap you of energy. Avoiding them is a key to the diet, and one of the secrets you discovered. You can just pick them at random, or if you are ambitious you can tie them into your overall diet narrative. The flip side of this is that there are also magic foods that should be encouraged. Again, they can be anything, even unhealthy or fattening foods. You can even recommend that people eat a huge helping of butter every day. Really!
#8 – Attack your critics. You may get some blow back from scientists and doctors about how pseudoscientific and unhealthy your diet is, and criticized because the research does not support your claims. Don’t worry about this – miracle claims and testimonials will shield you from any legitimate criticism. If you are feeling the pressure, however, then just attack your critics. Here again there are some good standbys, such as doctors don’t know anything about nutrition. All the diets that scientists have recommended before failed so they obviously don’t know what they are talking about. Scientists and doctors are all part of a giant conspiracy so they can’t be trusted. (Feel free to throw in mention of the AMA.) Your critics are just behind the times, or closed minded, or jealous of your success.
Making up your own fad diet can be fun and lucrative. All you have to do is relinquish any self-respect or integrity. You may even convince yourself that your diet is legitimate, because anyone can lose weight on almost any diet if they reduce calories. Testimonials will also be convincing to you (if you ignore the scientific evidence, which is recommended) and this will make you a more compelling promoter of your own diet.
The real trick is not becoming discouraged by the fact that fad diets are all bogus, they don’t produce sustainable results, they may be unhealthy, and they distort or ignore the actual science.
The practice of medicine, particularly our pharmaceutical and surgical interventions, involves a constant struggle between risk and benefit. If the physiology or anatomy of the human body is altered, even with the best of intentions, there is always a potential downside. There are certainly instances where the risk to benefit ratio is extremely favorable or unfavorable and the right recommendation is obvious, and unfortunately there are times when it isn’t entirely obvious what the next step should be. But there has been a trend of steady progress in regards to improved safety and efficacy over the past several decades.
The treatment of pain has of late been one of those areas where the picture is becoming a bit less cloudy. We are learning more and more about the potential negative outcomes related to the long term use of opioid medications, such as physical dependence, addiction and even chronic pain. The way that these drugs have been prescribed in many patients has caused more harm than expected, and in some instances more hurt than help. Doctors generally strive to alleviate pain and suffering but, once again, good intentions don’t decrease risk.
In the neonatal and young infant population, the management of pain has had a rocky history. I’ve written about pediatric pain in the past, in particular the potential difficulties in managing acute pain. I won’t go into detail (read my prior post), but we have truly come a long way since the days of performing major surgery on newborns without any analgesia at all. There are areas where we need to do better, however. Children are still less likely than adults to be adequately treated for pain.
But things have improved. And as more children receive appropriate management for pain, the side effects of that management must increasingly be dealt with by healthcare professionals, the patients and their families. One of the issues that is typically observed and managed in neonatal and pediatric intensive care units is physical dependence and the subsequent occurrence of withdrawal symptoms.
What are dependence and withdrawal?
No different than with adults, children experience pain for a variety of reasons, and some require the use of opioid medications for extended periods of time. Physical dependence with opioids can occur after just five to seven days of daily exposure. In the setting of the intensive care unit, there are children that are sometimes on medications for pain and sedation for weeks and even longer.
The American Academy of Pediatrics, in their 2014 clinical report on the subject, provides the following definition for physical dependence:
Physical dependence is a state of adaptation that is manifested by a drug class–specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.
Withdrawal symptoms occur when there is less of the drug in the patient’s system, which happens for essentially three reasons. As the patient recovers, opioid pain medication dosing is often decreased or spaced out. Intravenous medications are switched to oral formulations, which isn’t always a predictable transition. And sometimes the absorption of medications is decreased because of illness or injury to the gastrointestinal tract. Also, as referred to in the above definition, a medication that blocks the action of another drug, such as naloxone (Narcan) used for opioid overdose, can lead to withdrawal symptoms even when there hasn’t been a drop in the blood level.
Not every pediatric patient experiences withdrawal, and when they do it can be mild enough to escape the awareness of caregivers or to be blamed on something else. Is the baby fussy because of mild withdrawal from morphine, or is it just gas, for example. Of course the symptoms of more serious conditions can be blamed on withdrawal as well. When significant withdrawal does occur, it can interfere with recovery of the patient, expose them to increased risk of medication side effects and increase caregiver anxiety tremendously.
The most common and obvious changes seen during withdrawal in children are behavioral. Anxiety, agitation, difficulty sleeping and jitteriness are frequent examples. Also common in withdrawal are stiffening of the muscles, nausea and vomiting, poor feeding/appetite, increased respiratory and heart rate, elevated body temperature, sweating and elevated blood pressure.
Allow me to plant a seed and point out that there can be significant subjectivity to the assessment of most of these manifestations when caring for neonates and older infants. Was that just a little spit up or should we count it as an episode of vomiting? Is the baby not interested in the bottle because of withdrawal or because premature infants who have been ill sometimes just need more time to work up on feeds? Is the baby agitated, or just a little overstimulated? Perception is reality in the case of withdrawal.
There are validated assessment tools, the most well known probably being the modified Neonatal Abstinence Scoring System and the Withdrawal Assessment Tool-1 (WAT-1), that can used to help determine if an infant is undergoing symptoms of withdrawal. These tools can be used in the setting of potential withdrawal from opioids or benzodiazepine medications. The WAT-1, which I’ll focus on for reasons that will soon become clear, involves eleven items with a total possible score of twelve and is performed every twelve hours by a nurse caring for the patient.
How is the WAT-1 performed?
It breaks down as follows:
1. The nurse will review what happened over the previous twelve hours. Infants score a point (points are bad) for having had any loose/watery stools, wretching/gagging/vomiting, or temperature elevations above 37.8C (100F) up to a maximum of 3 points. Again, I’d like to point out the subjectivity inherent in this assessment. The nurse must decide if the baby’s stool is loose/watery compared to normal baby stools, which are often considered loose/watery. Also perfectly healthy babies have spit ups and brief gagging episodes all the time.
2. The nurse will then observe the baby for two minutes to get a sense of their behavioral state prior to any stimulation. A baby will only get 0 out of 5 possible points if they are asleep or awake and completely calm. They score a point for any crying, moderate to severe tremor (subjective), sweating, moderate to severe uncoordinated/repetitive movements (subjective), or more than one yawn or sneeze.
3. The nurse will then progressively stimulate the baby over one minute. They get a point for a moderate to severe startle reaction to touch or if they demonstrate increased muscle tone, both subjective assessments. Finally, the baby is left alone and the nurse documents how long it takes for the baby to calm. One point is scored if it takes the patient between two and five minutes. Greater than five minutes results in a score of two points.
I hope it doesn’t sound like I am trying to say that an assessment like the WAT-1 is worthless. It definitely isn’t. It is an improvement over previous methods which were much more cumbersome, involving many more items and more frequent assessments. And it is certainly less subjective than relying solely on the clinical judgement of the nurses and physicians. Although, tools like the WAT-1 are validated by comparing them to just such previous methods. They all must be taken with a grain of salt. Their greatest benefit is likely the fact that their use forces us to consider the possibility of withdrawal and to approach it systematically.
How is withdrawal managed?
The best approach to withdrawal in the pediatric population, and I imagine in adult patients as well, is anticipation and prevention of withdrawal if at all possible. If a child has been on a daily opioid for more than one week, although there are reports of withdrawal occurring after only five days, the medication should probably not be discontinued abruptly. And an assessment tool like the WAT-1 should be used consistently and as recommended.
It is common practice in hospitals to take into account how long the patient has been on a daily opioid, how high the doses are at the time weaning begins, concurrently administered medications (benzodiazepines, paralyzing agents, etc.) and the patient’s overall medical condition. It is also standard of care to follow an approved weaning protocol, generally with only one drug (if the patient is on more than one associated with withdrawal) being weaned at a time and the rapidity of the wean being determined by the length of time the patient had been on the drug. Naturally there are potential individual differences between patients, so signs and symptoms of withdrawal trump following a strict algorithm.
A typical approach would be to transition the patient to a stable dose of a longer acting form of the drug to be weaned, and then to decrease the amount by 10%-20% every couple of days if excessive rescue medication dosing hasn’t been needed. An approved assessment tool should be used to determine signs or symptoms of withdrawal and the need to delay a decrease in dosing or to give rescue dosing of a short acting version of the drug being weaned. A WAT-1 score greater than or equal to three, for example, is a typical cutoff for consideration of rescue dosing. Depending on the individual circumstances it can take a few days to weeks for a child to be successfully weaned and ready for discharge home.
Is there a role for acupuncture in the management of withdrawal in neonatal and pediatric intensive care units?
No, no there isn’t.
Weaning babies off of these medications can go smoothly or be a frustrating roller coaster ride. I confidently speak for parents, patients and medical professionals when I say that we would all love a safe and effective means of weaning these medications more quickly and with less occurrence of withdrawal. If such a means exists, there is no reason to think that it would consist of placing tiny steel needles through the skin or pressing on the ears in order to manipulate the flow of mystical energy through nonexistent pathways in the human body.
But thanks to a team of pediatric anesthesiologists at Stanford University, there is now another in a very long line of studies seemingly designed to be positive and to serve as fodder for believers looking for some science, any science, to hold up as proof of their beloved alternative medical belief system. This “research” was published in the October issue of Medical Acupuncture, a journal which as been discussed in the pages of Science-Based Medicine before, and not in a good way. The Editor-in-Chief happens to be Richard Niemtzow, the man who brought us “battlefield acupuncture.”
The authors start off by lamenting the need for painful procedures in young infants and the possible repercussions of poorly managed pain in the very young, such as an amplified pain response down the road. This is true…sort of. Some neonates exposed to a few painful experiences, such as heel sticks or circumcision, may have an exaggerated response to the jab from routine immunizations during the first year of life. But babies who experience repeated and prolonged pain, such as those riding vents for weeks or having major surgeries, are actually at risk of having blunted responses to pain during the first year of life. What is clear however is that pain causes remodeling of our response to it, perhaps for a long time, and we should do our best to reduce it whenever it is safe and possible to do so.
They also point out the downsides to our new and improved approach to pain management, which to be honest is simply the fact that we have an approach to pain management at all in neonates. But, as I discussed above, it can lead to dependence and withdrawal as well as possible acute side effects with overdoses such as respiratory suppression and death. They mention the possible need for adding additional medications to the mix, like clonidine, to help manage withdrawal. I didn’t get into that in detail, but it’s true. And like every other drug, there are potential risks when prescribed.
So far, so good.
The authors then go off track, although not unexpectedly, when they begin to praise the successes of acupuncture for withdrawal. They state that there is a long history of safety an efficacy starting with the incidental discovery of the indication in 1972 when “acupuncture anesthesia” was performed on a man addicted to opium in China. As Dr. Atwood’s excellent four part series explains, acupuncture anesthesia was and is a fiction, and anything associated with it is highly suspect.
They describe the protocol for acupuncture detoxification as established by the National Acupuncture Detoxification Association (NADA), which initially involved multiple points on the body and ears as well as electrical stimulation. Because of logistical issues and “reasons of efficiency in clinics”, both the electricity and the body points were eventually abandoned, luckily without any negative impact on the effectiveness of the treatments. That’s curious. The current NADA protocol consists of “bilateral ear acupuncture of the following five points: Kidney; Liver; Lung; Shen Men; and Sympathetic.
They claim that acupuncture treats anxiety, pain and agitation in a variety of pediatric contexts. After admitting that the only prior study related to pediatric withdrawal, which involved using acupressure in neonates suffering from abstinence syndrome, did not work, they point out the “suggestive trend toward less need for pharmacologic support.” All of this is used to bolster their case for an “exploration of the feasibility and efficacy of performing acupuncture on infants in the ICU.”
The authors enrolled ten neonates and infants in the study with the goal of determining the feasibility and efficacy of acupuncture as part of the management of withdrawal in the ICU. They obtained IRB approval from Stanford and informed consent from caregivers. These infants had few similarities. They were on different doses of medications or were on different medications entirely. One was on a ventilator and still getting doses of a paralyzing agent. They were at varying stages of their wean off of medications, and had extremely different reasons for why they were on these medications in the first place.
The treatment protocol consisted of NADA approved ear points but they also threw in some body points to “help stabilize symptoms of autonomic dysfunction.” They state this without a reference, as if it’s just a well-accepted thing that doctors do. Like stating that “fevers were treated with standard dosing of acetaminophen.” The authors did their own acupuncture and inserted the needles until they felt the De Qi sensation. After needling the babies, acupressure beads were placed on the points for 24 hours or until the next session. The NADA protocol they were supposedly following only calls for 30 minutes. All but one of the subjects had five sessions. That one went home after three days.
The authors report that all ten of the patients improved while receiving acupuncture and acupressure. Based on WAT-1 assessments, they needed fewer doses of rescue medications and their opioid and/or benzodiazepine infusions were weaned. There were no major complications, although one child suffered a minor skin abrasion from an acupressure bead. And although the nature of the study did not permit any statistical analysis, a survey of bedside caregivers (nursing, physicians, parents) revealed universal belief that the patients benefited from the intervention. The authors even provide several comments from the surveys, such as “Can we please do this for other patients?” and “She really likes her acupuncture.”
So to sum up, ten babies received an intervention for a highly subjective process, and were assessed without any blinding using a tool that is very susceptible to placebo. The authors of the study, two pediatric anesthesiologists, performed the intervention themselves at the bedside for all to see and included in their methods for no clear reason a means to make sure that anyone assessing the patients during a different shift knew which babies were involved. Then to cap it off, they included a likely non-anonymous survey that is even more subjective than the WAT-1 as part of their evidence for efficacy. I would have been shocked if the results were any less positive.
There are three possible explanations for the results of this study that I can think of. One is that acupuncture and/or acupressure works, not only for withdrawal from opioids but also benzodiazepines, and in a patients with a variety of medical histories. Or we accept that acupuncture functions as theatrical placebo and the biased perception of the caregivers led to the infants receiving fewer rescue medications and continuing on their weans. If this is the case, which in my opinion it almost certainly is, some or all of the infants may have not received medication that they truly needed. Finally, it all may just be the result of random factors. Placebo didn’t play a role, acupuncture doesn’t work, the process of withdrawal and weaning is highly variable and this was a very small number of subjects.
Regardless, I would love to have been privy to those IRB discussions and to the informed consent process. The latter isn’t described in the paper unfortunately. But this was not one of those papers where the researchers attempt to come up with a scientific sounding explanation for the proposed benefits of acupuncture. In addition to the “De Qi” reference, they state that “children may require less stimulation than adults because their Qi may be more responsive to stimuli.” So did they really discuss Qi with the parents? Did they mention that a better study looking at this very issue, which was published in the same journal in 2011 and even cited by the authors, showed no benefit whatsoever?
Why does this matter?
Although merely a collection of ten worthless anecdotes published in a journal that warps the concept of peer review beyond all meaning or recognition, there are already individual acupuncture practices touting it as evidence that acupuncture “truly is for everyone!”
Stanford researchers have found that acupuncture helps newborns in intensive care. Acupuncture has been effective for pain relief and sedation, the study showed. “High doses of opioids and benzodiazepines are often required for neonates and infants for the purposes of pain management and sedation. Cessation from medications lead to withdrawal symptoms and irritability. The researchers cite acupuncture’s documented ability to reduce pain, irritability and withdrawal symptoms in adults.”
Here is a website offering continuing medical education credits based on the study.
This study, a painfully unnecessary attempt to determine the feasibility and efficacy of acupuncture in neonatal and pediatric intensive care unit patients at risk of withdrawal, was a complete waste of time. You can not determine efficacy at all based on it and the question of feasibility was answered a long time ago. This study added nothing to our understanding of withdrawal or even of acupuncture.
Considering the reams of research showing that there are no benefits associated with the insertion of needles into, or pressing on, particular points on the body beyond placebo, it never should have happened. But it can’t be undone. It’s out there, adding to the cultural inertia of acupuncture. It will find its way to more websites and it will be cited in future poorly designed studies. Although less of a fuss was made about this paper than I would have expected, there are almost certainly many more people that are believers now because of it.
Although many forms of alternative medicine are like this to varying degrees, acupuncture really is the best Weeble of the bunch. It has proven time and time again to be able to right itself despite devastating blows in the literature. It’s nearly ubiquitous in academic centers and the modality that shruggies will usually cite when pressed for a reason for their lack of motivation. It’s widely accepted by the public as legitimate. Acupuncture doesn’t appear to be going anywhere anytime soon. In the meantime, why don’t you make supporting the Society for Science-Based Medicine one of your resolutions for 2015.
I have been saying for several years that if there is a pseudoscientific medical treatment that is especially vulnerable to critical analysis it’s homeopathy. There’s a lot of nonsense in the world of medicine, but homeopathy takes the prize. First, it is complete and utter nonsense.
There is no need to equivocate. Homeopathy violates basic scientific knowledge in physics, chemistry and biology. It is transparent witchcraft that cannot possibly work by any known or even semi-plausible mechanism. Further, clinical studies unsurprisingly show that it does not work, for anything.
And yet the public does not generally understand what homeopathy actually is. The most common belief is that homeopathy is natural or herbal medicine. Rather, homeopathy is based upon several dubious notions. The first is that like cures like, and idea based on sympathetic magic and not science or any knowledge of the real world. Further, the actual starting ingredients are based upon a fanciful and often absurd interpretation of this dubious notion, leading to things like using duck liver to treat the flu.
None of this actually matters, however, because most homeopathic remedies are diluted beyond the point that there is any chance of a single molecule of starting ingredient left. All of this is supposed to work, however, because the potion is “activated” by shaking it.
There is therefore a great opportunity to reduce the popularity of homeopathy simply by explaining to people what it is. This is why skeptics have started embracing homeopathy awareness week. We want people to be aware.
Articles in mainstream non-skeptical outlets are appearing, pointing out the utter ridiculousness of homeopathy.
There have been a number of comprehensive reviews of homeopathy in recent years, all concluding that there is no evidence or plausibility to homeopathy. Even the Swiss report, which was trumped up by homeopaths, had to conclude that there is no good clinical evidence to support homeopathy.
2014 added a new review to the list, by Australia’s National Health and Medical Research Council (NHMRC). They concluded:
Based on all the evidence considered, there were no health conditions for which there was reliable evidence that homeopathy was effective. No good-quality, well-designed studies with enough participants for a meaningful result reported either that homeopathy caused greater health improvements than placebo, or caused health improvements equal to those of another treatment.
Homeopaths tried to criticize the report, as they always do, but to no avail. The evidence is the evidence.
Also in Australia a Federal court found that claims being made by Homeopathy Plus! for their homeopathic vaccines was misleading and dangerous. They found:
The Court found that Homeopathy Plus! and Ms Sheffield engaged in misleading and deceptive conduct and made false or misleading representations by publishing statements on the Homeopathy Plus website to the effect that:
when in fact the whooping cough vaccine is effective in protecting a significant majority of people from contracting whooping cough.
As a result, we are making progress, especially in the UK. Michael Marshall from the Good Thinking Society reports:
In 2010, when I first became involved in alternative health activism, the NHS funded no fewer than five homeopathic hospitals; today all have either closed or faced a serious threat to their existence. Recent figures, obtained through a freedom of information request by the Nightingale Collaboration, show an encouraging swing away from homeopathy, with prescriptions falling from a high of 170,000 per annum in 1996 to just over 10,000 last year.
As I wrote above, there is no need to equivocate. Homeopathy is a dangerous scam. It should not be sold, and should not be supported in any way by governments, universities, or hospitals. There is no need to research it further, that would be a complete waste of resources. It is transparent witchcraft that belongs to a prescientific age.
At least the word seems to be getting out.
A wish a happy new year to all my readers.
Happy New Year! Today’s post dusts off some old material, repackaged and updated for 2015.
New Year, New You, right? We’re just into 2015, and you’ve resolved to finally get serious about your health. Starting today. But first need to cleanse yourself, eliminating last year’s lifestyle and dietary sins. You’ve seen the ads and the Facebook links, all suggesting you need a “detox”, “cleanse” or “flush” to be healthy. Supplements, tea, homeopathy, coffee enemas, ear candles, and footbaths promise you a detoxified body. Amazon has entire detox and cleansing categories in supplements and books. The descriptions all suggests detoxing will deliver a renewed body and better health – it’s only seven days and $49.95 away. Dr. Oz has several detox plans – you just need to decide which one. The local naturopath sells detoxification protocols, including vitamin drips and chelation. Even your pharmacy probably has a wall of products for sale. Wouldn’t a purification from your sins of 2014 be a good idea to start the year? Unfortunately, there’s something very important that detox promoters aren’t telling you:“Detox” isn’t Real
“Detox” is a legitimate medical term that has been turned into a marketing strategy – all designed to treat a nonexistent condition. Real detoxification isn’t ordered from a menu of alternative health treatments, or assembled from ingredients in your pantry. Actual detoxification is provided in hospitals under life-threatening circumstances – usually when there are dangerous levels of drugs, alcohol, or other poisons. These are not products you can purchase in a pharmacy for personal use. What you’re seeing promoted as “detox” is using medical terminology, but only to give the perception of scientific legitimacy to medically useless products and services. Fake detox is built around a number of easily debunked premises. Once you can spot the flaws, it’s easy to tell fact from fiction:Premise one: Our bodies are accumulating toxins, so we need to detoxify
There’s a reason we fall for the marketing of detoxification – we seem hardwired to believe we need it, perhaps related to our susceptibility to ideas of sympathetic magic. Purification rituals date back to the earliest reaches of recorded history. The idea that we’re somehow poisoning ourselves and we need to atone for our sins seems to be a part of human nature, which may explain why it’s still a part of most of the world’s religions. It’s not miasmas or perhaps sin that we’re as worried about today, however. As our knowledge of biology grew, these fears manifested as “autointoxication.” Clean out the bowels, went the theory, and you could cure any illness. Science discarded autointoxication by the 1900′s as we gained a better understanding of anatomy, physiology, and the true cause of disease. Yet the term persists today, but now it’s used to sell useless products and services. Today’s version of autointoxication argues that some combination of food additives, salt, meat, fluoride, prescription drugs, smog, vaccine ingredients, GMOs, and perhaps last night’s bottle of wine are causing a buildup of “toxins” in the body. And don’t forget gluten. Gluten is the new evil and therefore, is now a toxin. So what is the actual “toxin” causing you harm? Detox kits and treatments never name the toxins that they remove, because they’ve never been tested to remove toxins. For example, Renew Life promises you:
CleanseSMART is a 2 part, 30 day, advanced herbal cleansing program. It is formulated to stimulate the detoxification process of the body’s 7 channels of elimination: the liver, lungs, colon, kidneys, blood, skin, and lymphatic system. In today’s toxic world, cleansing and detoxification is a necessity. Toxins enter our body daily through the air we breathe, the food we eat, and the water we drink. Over time, these toxins build up and slowly start to affect our health in a negative way.
Through cleansing and detoxification, you enable your body to better process this toxic load. Reducing the toxic load in your body decreases the risk of developing chronic health problems, improves overall health and immune response, and can increase energy levels. CleanseSMART works to cleanse and detoxify the entire body, but with focus on the body’s two main detoxification pathways – the liver and the colon. CleanseSMART is essential for helping eliminate constipation and improving bowel health.
Note the vague language. Toxins are alluded to – but not named. It sounds somewhat plausible, but is non-specific. Note that even if you’re well (and presumably toxin free?) a detox is still recommended.
The colon remains ground zero for detox advocates. They argue that some sort of toxic sludge (sometimes called a mucoid plaque) is accumulating in the colon, making it a breeding ground for parasites, Candida (yeast) and other nastiness. Fortunately, science tells us otherwise: mucoid plaques and toxic sludge simply do not exist. It’s a made-up idea to sell detoxification treatments. Ask any gastroenterologist (who look inside colons for a living) if they’ve ever seen one. There isn’t a single case that’s been documented in the medical literature. Not one.Premise two: Illness is the result of chemical toxins
Marketing materials for detox treatments typically describe an array of symptoms and diseases linked to toxin buildup: A few that are general enough to apply to anyone (e.g., headache, fatigue, insomnia, hunger) with a few specifics to frighten you (cancer, etc.) Which toxins cause which disease is missing, and how the toxins cause the symptoms is never actually explained. Here again we see the contrast with real science. To establish that even a single chemical can cause disease requires a significant amount of research (i.e., the entire field of epidemiology). Despite the variety of toxins that are claimed to be causing your illness, marketing claims for detox treatments always fail to link specific toxins to specific symptoms or illnesses. That’s because they can’t – there is no scientific evidence to show that detox treatments have any useful medical effects.
The reality is that our bodies are constantly being exposed to a huge variety of natural and synthetic chemicals. The presence of any chemical in the body, (natural or synthetic) does not mean that it is doing harm. Many naturally-derived substances can be exceptionally toxic, and consequently the human body has evolved a remarkable system of defenses and mechanisms to defend against, and remove unwanted substances. The skin, kidneys, lymphatic system, our gastrointestinal system, and most importantly, the liver make up our astoundingly complex and sophisticated intrinsic detoxification system. Importantly, the dose makes the poison – even water can be toxic (dilutional hyponatremia) when consumed in excessive amounts.
Advocates for detox typically describe the liver and kidney as acting like filters, where toxins are physically captured and retained. It’s argued that these organs to be cleaned out periodically, like you’d rinse out a sponge, or change the air filter in your car. But the reality is the kidney and liver don’t work this way. The liver performs a series of chemical reactions to convert toxic substances into ones that can be eliminated in bile, or the kidneys. The liver is self-cleansing – toxins don’t accumulate in it, and unless you have documented liver disease, it generally functions without any problem. The kidney excretes waste products into the urine – otherwise the substance stays in the blood. Anyone that suggests these organs need a “cleanse” is demonstrating their ignorance of human physiology, metabolism, and toxicology.Premise three: Detox treatments remove toxins
A search of the medical literature for clinical studies of detox kits provides the following result:No Items Found
There is no credible evidence to demonstrate that detox kits do anything at all. They have not been shown to remove remove “toxins” or offer any health benefits. The same can be said for alternative medicine treatments like coffee enemas – there is no credible evidence to support claims that coffee enemas help the body to “detoxify” compounds, or help the liver function more effectively. Vitamin injections are another treatment that fail to offer meaningful benefits to consumers, and have no beneficial effect on the ability of your liver or kidneys to work effectively. Chelation injections are touted as a cure-all for all kinds of illnesses, but unlike real chelation, that’s administered in hospitals for real cases of poisoning, naturopath chelation is not science-based and doesn’t seem to do much of anything. The onus is on promoters of detox to show their kits and potions actually deliver as promised – but they don’t, because they haven’t done the studies.Is Detox Harmful?
If they provide no benefit, is there the potential for detox treatments to harm?
When it comes to simple dietary changes, there’s little evidence of harm. Eating more quinoa and kale, and less processed and refined foods is reasonable dietary advice for everyone. Homeopathic “detox” is also likely safe – with no active ingredients, homeopathy is an elaborate placebo system. As you get into more unorthodox detox treatments that actually contain active ingredients, there is the potential for harm. Coffee enemas are considered unsafe and should be avoided. Harms such as septicemia (bacteria in the bloodstream), rectal perforation, and electrolyte abnormalities have been reported. Even deaths. Vitamin injections won’t provide you with any medical benefits but don’t seem as risky, as long as you trust the sterile technique of your alternative provider. However, given some naturopaths seem to be willing to inject products intended for oral use, you might want to think carefully about taking a vitamin injection or chelation treatment, especially when there’s no upside – only risk to your health and to your wallet.
What about the detox kits? Contents vary, but typically contain two categories of ingredients:
Side effects can continue once a detox ends. Some people experience post-detox effects like nausea and diarrhea. Advocate call these “cleansing reactions” and will assure you it’s “toxins leaving the body”. A more plausible, science-based explanation is that this is a consequence of restarting the digestion process after a period of catharsis, where, depending on the extent and duration of fasting, little to no digestion occurred, and the normal gastrointestinal flora may have been severely disrupted. It’s the same effect seen in hospitalized patients who have difficulty initially digesting food after being fed intravenously. The detox ingredients, and resulting catharsis, may irritate the colon to such an extent that it may take time to return to normal.
Immediate weight loss is not uncommon after a detox, especially one that involves a laxative. Unfortunately this is usually due to losses in water and possibly muscle tissue, depending on the how disruptive the detox was to normal body function Regardless of the weight loss, the body will move back to its pre-detox weight over time if diet and activity levels remain the same.Red Flags for Detox Quackery
I’ve pulled a few advertisements from some of the most popular proponents of health quackery, and circled the red flags for quackery:
Homeopathic Detox: Homeopathy is an elaborate placebo system. Heel is a homeopathy manufacturer recently ceased operations in Canada and the USA under threat of a class action lawsuit. Now a new manufacturer is reselling the same products. They have no medicinal ingredients in them. Dana Ullman is a homeopathy proponent who often contributes to the Huffington Post, a site that more often than not gets the science wrong. In this advertisement from Ullman’s site, the Heel “Homeopathic Detox Kit” is now just called a “Cleanse Kit”:
Natural News: Mike Adams of Natural News is a conspiracy theorist and purveyor of pseudoscience and bad health information. It’s wise to ignore anything you read at Natural News. Here Adams uses the naturalistic fallacy to promote the idea that GMOs are toxic, when there’s zero evidence that’s the case:
The Food Babe: Vani Hari also promotes the nonsensical idea of “detox”. Her writing suggests she lacks an understanding of medicine, nutrition, or basic biology.
Any product or service with the words “detox” or “cleanse” in the name is only truly effective at cleansing your wallet of cash. Alternative medicine’s ideas of detoxification and cleansing have no basis in reality. There’s no published evidence to suggest that detox treatments, kits or rituals have any effect on our body’s ability to eliminate waste products effectively. They do have the ability to harm however – not only direct effects, like coffee enemas and purgatives, but they distract and confuse people about how the body actually works and what we need to do to keep it healthy. “Detox” focuses attention on irrelevant issues, giving the impression that you can undo lifestyle decisions with quick fixes. Improved health isn’t found in a box of herbs, a bottle of homeopathy, or a bag of coffee flushed into your rectum. The lifestyle implications of a poor diet, lack of exercise, smoking, lack of sleep, and alcohol or drug use cannot simply be flushed or purged away. Our kidneys and liver don’t need a detox treatment. If anyone suggests a detox or cleanse to you, remember that you’re hearing a marketing pitch for an imaginary condition.
There is an ideological subculture that is motivated to blame all the perceived ills of the world on environmental factors and corporate/government malfeasance. Often this serves a deeper ideological drive, which can be anti-vaccine, extreme environmentalism, or anti-GMO. The latest environmental bogeyman making the rounds is glyphosate, which is being blamed for (you guessed it) autism.
Glyphosate is the active ingredient in the herbicide Roundup. It has been widely used for about 40 years, and with the introduction of GM crops that are Roundup resistant, its use has increased significantly in the last 20 years. It has therefore become a popular target for anti-GMO fearmongering.
Glyphosate is one of the least toxic herbicides used. It inhibits the enzyme 5-enolpyruvylshikimic acid-3-phosphate synthase which interferes with the shikimic pathway in plants, resulting in the accumulation of shikimic acid in plant tissues and plant death. This enzyme and pathway do not exist in animals, which is why toxicity is so low. Still, chemicals can have multiple effects and so toxicity needs to be directly measured and its epidemiology studied.
Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies.
Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA.
As pesticides go, glyphosate has very low toxicity, and any dose a person is likely to get exposed to is well below the safety limits. A 2012 review looking specifically at reproductive and developmental effects found:
In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.
This includes exposure of farm workers spraying glyphosate, as the chemical is very poorly absorbed through the skin.
A 2011 review of epidemiological studies looking at the association of glyphosate and all non-cancer health outcomes found:
Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0.
Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate.
In short there is no evidence for any significant glyphosate toxicity. It breaks down quickly in soil, although can get into ground water, but environmental levels are orders of magnitude lower that accepted safety limits.
The current article spreading fears about glyphosate cites the work of Stephanie Seneff, making a clear argument from authority:
For over three decades, Stephanie Seneff, PhD, has researched biology and technology, over the years publishing over 170 scholarly peer-reviewed articles. In recent years she has concentrated on the relationship between nutrition and health, tackling such topics as Alzheimer’s, autism, and cardiovascular diseases, as well as the impact of nutritional deficiencies and environmental toxins on human health.
Seneff, however, has not actually performed any research into glyphosate. She is “a Senior Research Scientist at the MIT Computer Science and Artificial Intelligence Laboratory.” She is also an anti-GMO activist. That does not mean she is wrong – it just means it is misleading to cite her as a researcher and authority. He has published only speculations and gives many presentations, but has not new data.
The dramatic claim she is currently making, the one prompting many scary headlines, is that “Half of All Children Will Be Autistic by 2025.” This is not based on any new research. It is simply a naive extrapolation of current trends indefinitely into the future – which is always dubious. Seneff also is naively equating correlation with causation. Here is her big evidence, in the graph on the left:
She then assumes correlation is causation – this is the same error the anti-vaccine ideologues make when looking at thimerosal and autism (although conveniently ignore the lack of correlation after the removal of thimerosal from the routine childhood vaccine schedule). The graph on the right, however, nicely demonstrates that correlation is not necessarily due to causation.
Seneff makes many other dubious claims as well:
“Dr. Seneff points out, however, that our gut bacteria do have this pathway, and that’s crucial because these bacteria supply our body with crucial amino acids.”
This is pure speculation. There is no evidence that glyphosate has any adverse effect on gut bacteria, or that such effects are linked to any disease.
She makes further claims based purely on correlation as well, including blaming glyphosate for celiac and gluten sensitivity.
The article also repeats a common anti-GMO claim, that wheat in the US is routinely sprayed with glyphosate just prior to harvest. There is never any source given for this claim, and a careful investigation reveals that it is untrue.
Dr. Seneff gives every indication of being an anti-GMO ideologue. She is not a biologist, but rather is a computer scientist, and yet she is being presented as an expert. She has also not conducted any original research, but is spreading fears about glyphosate based on pure speculation, bad science and bad logic.
Meanwhile, numerous published systematic reviews show clear evidence that glyphosate has very low toxicity. More careful study when it comes to any agent being used as heavily as glyphosate is always welcome. Science is complicated, and it is always a good idea to consider factors that may have been previously missed. However, failure to show any adverse effect from glyphosate in epidemiological studies is very reassuring. Given its widespread use, any adverse effect must be tiny or non-existent to be missed by the evidence we have so far.
The evidence, however, will not stop ideologues from cherry picking, misusing evidence, presenting pure speculation as if it were evidence, assuming causation from correlation, and generally fearmongering about a safe chemical in order to grind their ideological axe.
Living things move. In fact our visual system uses the way things move to decide whether or not an object has agency and is able to move on its own. In the pre-technological world only things that are alive have agency, but in the technological era we have animatronics and animated video that can mimic the movement of living things and trick our brains into treating objects or representations as if they are alive.
There are several applications for detecting the signatures of life. So far such efforts have focused mainly on chemical signatures – looking for the products of biochemistry. Researchers publishing in PNAS, however, have taken a new approach. They are trying to detect the motion signatures of life at a microscopic scale.
They use nanoscale motion detectors that are actually tiny cantilevers. Even a single bacterium twirling its flagella can cause the cantilever to move. Lasers then detect the motion of the cantilever, and that motion is analyzed for the signatures of life. The researchers tested their setup on soil and pond water, and found that it accurately detected microscopic life. They then used drugs to kill any living cells, and the detection stopped.
The most immediate application of this technology would be in drug development and research. If, for example, an antibiotic or anti-cancer agent is being studied, it could quickly be detected if the bacteria or cancer cells were dying off. This could accelerate the process of such research.
Perhaps the more interesting application, and of course the one that the press release focused on, is detecting life in extreme conditions, including extraterrestrial life. Such an apparatus could, for example, be included in a Mars probe, or one to Europa or Enceladus. If the Martian soil contains any living microorganisms, regardless of their chemistry, this technique might be able to detect them.
In fact, movement may be a more universal signature of living things than any particular chemical reaction. We currently only have one example of biochemistry, and that is from life on Earth, all of which is related. Scientists and science fiction writers have speculated about what kinds of alien biochemistry might exist, but it is all speculation. It’s interesting to think about silicon-based life instead of carbon, for example. Some doubt the plausibility of this because silicon, while similar to carbon, does not have its chemical flexibility. Others have speculated about hydrogen breathers, methane breathers, and life in conditions vastly different from those on Earth.
Using chemical signatures we can look for what we know, but might completely miss the unknown.
With movement, all we would need to have a suspicion of life is any movement, particularly movement that is non-inertial, meaning that it cannot be explained by passive movement following the laws of physics.
I find it hopeful that this technology has some immediate practical applications, such as in drug development. This makes it more likely that it will be fully developed, and therefore be available for less commercially viable applications.
“A Book of Verses underneath the Bough,
A Jug of Wine, a Loaf of Bread–and Thou
Beside me singing in the Wilderness–
Oh, Wilderness were Paradise enow!”
– The Rubaiyat of Omar Khayyam
Alcoholic beverages have always inspired strong opinions pro and con. Omar Khayyam included wine in his vision of Paradise; Carrie Nation took a hatchet to saloons. Humans have been drinking alcoholic beverages for at least 12,000 years. In earlier eras beer and wine were dietary staples that provided essential calories and were safer to drink than water. Early cultures worshipped wine deities; today, some religions ban all forms of alcohol while others embrace red wine as an essential part of a holy sacrament. Alcoholic beverages are widely used as an accompaniment to meals and as a social lubricant (as Ogden Nash put it, “Candy is dandy, but liquor is quicker”). Prohibition didn’t work.
It’s always good when opinions can be backed up by scientific evidence. Those who drink, especially wine lovers, can bolster their personal preference with the evidence from recent studies showing that moderate alcohol consumption prolongs life and improves health in various ways. Those who prefer not to drink are being told they can get the same benefits from resveratrol, a component of red wine. Just how good is the evidence, and what does it really tell us?
Benefits of Alcohol
According to this website, there is evidence that drinking wine provides these health benefits:
This sounds very encouraging. Is it reason to rush out and buy stock in a vineyard or build a wine cellar? To make you start drinking if you don’t already? To make you buy resveratrol supplements to get the benefits of wine without the intoxication?
Risks of alcohol
Maybe you shouldn’t jump on the bandwagon just yet. According to another website, there is evidence for an even longer list of health problems caused by alcohol:
That list is incomplete, leaving out things like fetal alcohol syndrome. And what about the social costs of drunkenness, alcohol-fueled violence, addiction, and accidents?
Wine and other alcoholic beverages have been used for medicinal purposes throughout history, but modern science-based interest began with the discovery of the French paradox. Researchers studying risk factors for coronary disease discovered that after controlling for known risk factors, heart disease was less common in France than in the US; and it was proposed that the much larger consumption of red wine in France might explain the difference. The average annual consumption of red wine was 60-70 liters in France compared to 5-10 liters in the US.
Just how credible is the research supporting the claims of health benefits? Does it extend to drinking beer and other forms of alcohol, or just red wine? If moderate intake is beneficial, how much is enough to get the benefits? Let’s take a closer look.
Some people decry the use of Wikipedia as a source, but in this case the Wikipedia article on long-term effects of alcohol consumption is an excellent place to start. It provides an exhaustive overview of the research on alcohol with plenty of citations. I’ll try to summarize what we know.
There is considerable high-quality evidence that moderate drinkers live longer than either abstainers or heavy drinkers, but there are some caveats. The subject does not lend itself to randomized placebo controlled studies, so we have to rely on other, less certain kinds of evidence. That’s not a problem per se. We had the same problem in studying the health effects of smoking, but in that case we had a mountain of corroboratory evidence from various kinds of studies and basic science that led to a firm conclusion. The evidence on alcohol has not yet reached a comparable consistency or critical mass. It relies mainly on epidemiologic studies, a type of research that has a lot of drawbacks. Correlation doesn’t necessarily mean causation. We can never be sure all possible confounders have been eliminated; for instance, people who drink red wine might belong to a higher social status and have a healthier diet and lifestyle than the average nondrinker. And there are studies from non-Western cultures that found the opposite: no benefit and even possible harm from alcohol consumption. Most importantly, there is no evidence that people who don’t drink would improve their longevity if they started drinking. Or that people who do drink would decrease their longevity if they stopped drinking.
Many of the studies looked at total alcohol consumption without breaking it down into wine, beer, and other spirits. When red wine was singled out, multiple studies found it was more beneficial than other alcoholic drinks, even white wine. It was suggested that this might be due to the high polyphenol content of red wine. Antioxidant polyphenols are concentrated in the skin and seeds of the grape, which are omitted from white wine. Alcohol is a pro-oxidant, but the polyphenol content makes red wine an overall antioxidant. Older wine has a lower antioxidant capacity than younger wine. Red grape juice also contains polyphenols and shows some of the same antioxidant benefits as red wine. Polyphenols in red wine inhibit platelet aggregation; this effect is only seen when the skins and seeds are both used, so there may be a synergistic effect between different components. Polyphenols relax arteries and reduce blood pressure; this effect occurs with alcohol-free red wine but the opposite effect occurs with alcohol. The evidence for the superiority of red wine is inconsistent: some studies have indicated that other alcoholic beverages are equally beneficial.
Might it make a difference whether alcohol is a regular accompaniment to meals in a culture consuming a Mediterranean diet versus drinking in non-meal settings or with other kinds of food? That hasn’t been tested. We simply don’t know. And we’re not likely to find out, since randomized controlled trials can’t be done. We are left with guesswork based on epidemiologic studies and basic science.
The benefits and risks for cancer are not clear. Overconsumption of alcohol has been correlated with several types of cancer, and moderate consumption is correlated with a higher risk of breast cancer. One study found that red wine reduced DNA damage but alcohol alone did not. The list above of benefits includes “cuts risk of colon cancer,” citing a 2005 study showing that moderate drinkers of red wine were 45% less likely to develop colon cancer. But that is belied by a 2011 meta-analysis that found strong evidence for an association between alcohol and increased risk of colon cancer.
Sirtuin is an enzyme associated with increased lifespan in mice but not yet verified for humans. The resveratrol in red wine is thought to increase sirtuin levels. I have written about resveratrol before. The longevity benefits of massive doses of resveratrol for obese mice are impressive, but there is little evidence that resveratrol supplements benefit humans. This 2013 review of clinical trials concluded:
The relevance of the huge output of in vitro and animal studies looking at the health benefits of RES is unclear. Scientific literature is filled with plenty of studies where unrealistic assay conditions have led to many effects and mechanisms that are far from being confirmed in humans.
As for the evidence that wine slows cognitive decline, this 2012 review shows that alcohol has both a neurotoxic and neuroprotective effect, and warns that study findings should be interpreted with caution.
Can (should?) alcoholic beverages be part of a healthy diet? As usual, science doesn’t give us the kind of clear-cut answers we would like.
There are known risks to heavy use of alcohol. Moderate use of alcohol has been associated with improved health and longevity; but the evidence is not entirely consistent or conclusive, and the benefits may be from components of red wine rather than from alcohol per se. Claims that the benefits of red wine can be achieved with resveratrol supplements are premature. The optimum dose of wine or alcohol has not been established.
There are plenty of reasons not to drink to excess; but there is no firm evidence-based consensus about how much is too much. In my opinion, if you don’t drink, the prospect of health benefits is not reason enough to start. If you do drink responsibly and in moderation, you can reassure yourself that the health benefits may outweigh the risks, especially if you drink red wine.
Another Christmas has come and gone, surprisingly fast, as always. I had thought that it might make a good “last of 2014″ post—well, last of 2014 for me, anyway; Harriet and Steve, at least, will be posting before 2014 ends—to do an end of year list of the best and worst of the year. Unfortunately, there remains a pressing issue that doesn’t permit that, some unfinished business, if you will. I’m referring to a story I commented on last week, specifically the credulously reported story of how 86-year-old hockey legend Gordie Howe is doing a lot better after having undergone an experimental stem cell therapy for his recent stroke. As you might recall at the time, I saw a lot of holes in the story. It turns out that over the last week there have been developments that allow me to fill in some of those holes. Unfortunately, other holes still remain.
First, a brief recap is in order. (You can click here for a more detailed timeline). Gordie Howe suffered a massive stroke on October 26, leaving him hemiplegic and with serious speech impairment. Since then, judging from various media reports, he has been slowly improving, although not without significant setback. We also know that Howe suffers from significant dementia. Out of the blue, press release issued on December 19 by the the Howe family announced that on December 8 and 9, Gordie Howe “underwent a two-day, non-surgical treatment at Novastem’s medical facility. The treatment included neural stem cells injected into the spinal canal on Day 1 and mesenchymal stem cells by intravenous infusion on Day 2.” His response was described as “truly miraculous,” although, as I pointed out in my post, it’s not clear exactly what “miraculous” meant, given conflicting contemporaneous news accounts before the Howe family press release, particularly his hospitalization from December 1 to 3 for a suspected stroke that turned out to be dehydration.
I noted a number of problems with the story, the first of which is that Howe was clearly not eligible for the clinical trial offered by Stemedica, a company in San Diego that manufactured the stem cells used. Another glaring issue was my inability to locate any description of an actual clinical trial for stroke offered by Novastem. I could find no such trial listed in ClinicalTrials.gov, and you, our intrepid readers, searched the registry maintained by the Federal Commission for the Protection Against Sanitary Risk (COFEPRIS) and were not able to find any registered clinical trials for stroke being carried out by Clínica Santa Clarita, the clinic Novastem operates. What you, our intrepid readers, did find were trials of stem cells for: COPD, osteoarthritis, type II diabetes, metabolic syndrome, and erectile dysfunction (of course). I did the search again over the weekend, and there were no further trials that I could find.
So it was that I concluded my post having grave doubts that there actually was a clinical trial run by Novastem using Stemedica’s allogeneic mesenchymal stem to treat stroke. To me, it all looked very fishy, as though Dr. Maynard Howe (CEO) and Dave McGuigan (VP) of Stemedica Cell Technologies, knowing that Gordie Howe was not eligible for their clinical trial for stroke, given that Howe’s stroke was less than two months prior and the trial required that the stroke be six months old and that no neurologic improvement had occurred for two months, had shunted him to Novastem to be treated. Looking at Novastem’s website, in marked contrast to that of Stemedica, I saw no evidence of clinical trial activity at all, other than following up with patients by keeping in touch with their doctors. What I did see was (to me, at least) a very dubious-appearing stem cell clinic that charged patients large amounts of money for stem cells, cash on the barrelhead. (Seriously, Novastem only accepts cash or money transfers.) With Christmas fast approaching, I did not expect to find out anything more about this story before the end of the year.
My expectation was upended on Christmas Eve.In which I am sent a press release
On the afternoon of December 24, as I was preparing to head over to my aunt’s house for the traditional Gorski family Christmas Eve celebration, I received an e-mail from a woman named Kimberly Stoddard, who represents The Townsend Team, a marketing and branding firm representing Stemedica. Ms. Stoddard referred me to a press release entitled Novastem Treats First Patient Using Stemedica’s Mesenchymal and Neural Stem Cell Combination Therapy for Ischemic Stroke:
TIJUANA, Mexico, Dec. 24, 2014 /PRNewswire/ — Novastem, a leader in regenerative medicine, announces the treatment of its first patient in its study for ischemic stroke at Clinica Santa Clarita. According to the American Stroke Association, ischemic strokes account for 87 percent of all stroke cases. Novastem continues to enroll qualified patients in the study, entitled “Internal Research Protocol in Combination Therapy of Intravenous Administration of Allogeneic Mesenchymal Stem Cells and Intrathecal Administration of Neural Stem Cells in Patients with Motor Aphasia due to Ischemic Stroke.” All participants receive a unique, combination therapy using a method covered by a United States patent owned by Stemedica Cell Technologies for the therapeutic use of its allogeneic, ischemia-tolerant mesenchymal and neural stem cells.
My first reaction went along the lines of, “Well, that’s odd. Who issues a press release like this on Christmas Eve? Nobody’s paying attention now.” My second thought was a speculation, “Well, maybe that was the point.” My third question was whether this press release was a reaction to the skeptical posts about Gordie Howe’s treatment with stem cells by Paul Koepfler and myself. In checking to see of Dr. Koepfler had written anything else, I found a followup post by him dated December 23 and entitled Response from Stemedica on Questions on Stem Cell Treatment of Howe. It’s not very informative, its only new information being that Stemedica didn’t write the press release (its author was later revealed to be Gordie Howe’s son Murray) and that “Stemedica is not a sponsor of the clinical trial referenced below; that is Novastem…”
And now we have Novastem and Stemedica’s joint press release.
It was immediately obvious to me (and anyone else who had paid attention to the stories about Gordie Howe) that this first patient treated was, in fact, Gordie Howe, although the press release quite properly did not name him. One thing I wrote in my original post that this press release did confirm for me is that the principal investigator (PI) of this “trial,” if trial it is, appears grossly unqualified to be running a clinical trial on something as tricky as testing whether stem cells might help stroke victims. If you don’t believe me, take a look at Dr. Clemente Humberto Gil Zúñiga’s CV posted on the Novastem website. He’s a geriatrician who practices at Hospital Angeles Tijuana and appears to possess no relevant clinical trial experience that I can find listed. Certainly his publication record shows nothing related to stem cell biology or clinical trials.
I’m a clinical trial maven. That’s why I had hoped to learn a bit more about the trial design, but the press release, not surprisingly, reveals little. Still, there are clues here. First, off, this trial is designed to examine the effect of this stem cell treatment on aphasia. Briefly, the general term “aphasia” describes acquired speech/language difficulties due to brain injury or damage in which part or all of speech is impaired with no affect on intelligence. For example, in simple terms a patient with expressive aphasia can understand what others say and knows what he wants to say but just can’t say it. I have personally witnessed a family member with this after a stroke. It’s incredibly frustrating to the patient. There are other forms of aphasia, such as receptive aphasia, but it’s not important for purposes of this post to describe them now. All you need to know is that various forms of aphasia are very common sequelae of strokes. It struck me as odd that Gordie Howe would be on an aphasia trial, because (1) his post-stroke impairments go way beyond aphasia, judging from the news reports and (2) he suffers from significant dementia, which would make determining aphasia scores difficult. We don’t know for sure how bad Howe’s dementia is, but in some news reports I’ve seen it’s been described as “severe.”
Next, there is this part of the title of the protocol, “Internal Research Protocol.” Right away this tells us that there is no external funding; it’s an internal protocol. Next, if we look at the paragraph above, we see a curious sentence stating that the “protocol is approved by the Research Ethics Committee of Clinica Santa Clarita, which is federally registered and licensed by the Federal Commission for the Protection against Sanitary Risk (COFEPRIS), a division of Mexico’s Ministry of Health.” What does this mean? Not being familiar with Mexican law with respect to clinical trials, as I am with US law, I am struck by how this is described. In the US, we would say that a trial is IRB approved (Institutional Review Board), that there is an IND (investigational new drug) application, and that the trial is registered with the FDA, which presumably any company would do because trials being used as a basis for drug approval have to be registered with the FDA and conform to all the rules for clinical trials, including the Common Rule. In this press release, we see from the sentence structure that it is the clinic, Clinica Santa Clarita, that is “federally registered and licensed by the Federal Commission for the Protection against Sanitary Risk (COFEPRIS), a division of Mexico’s Ministry of Health,” not the trial. I suspected that this sort of registration is not the equivalent of what goes on in the US. Boy, was I correct, far more so than I thought! I’ll explain in the last section, when I look at this trial in more detail. First, however, I want to address a news story published Friday.What really happened?
On Friday, a reporter who’s interviewed me before, Bradley Fikes, published a news story about Gordie Howe in U-T San Diego entitled Did stem cells really help Gordie Howe? This is the first—and so far only—attempt by a mainstream media outlet that I’ve seen to cast a skeptical eye on the whole story as presented. In the story, Fikes reports a number of disturbing aspects of this case.
First, we learn from Dr. Murray Howe, Gordie’s son, how he’s doing:
Howe, 86, suffered the stroke in late October, leaving him unable to walk and disoriented. He began improving within hours after receiving the stem cells in early December, said Dr. Murray Howe, a radiologist and one of Howe’s sons. For example, Howe insisted on walking to the bathroom, which he previously could not do.
“If I did not witness my father’s astonishing response, I would not have believed it myself,” Murray Howe said by email Thursday. “Our father had one foot in the grave on December 1. He could not walk, and was barely able to talk or eat.”
“Our father’s progress continues,” the email continued. “Today, Christmas, I spoke with him on FaceTime. I asked him what Santa brought him. He said ‘A headache.’ I told him I was flying down to see him in a week. He said, ‘Thanks for the warning.’”
Yes, Gordie Howe did appear to have “one foot in the grave” on December 1. I even reported it in my last post that he looked bad then and everyone thought that he had had another big stroke. Fortunately, he was just dehydrated and rapidly improved with hydration, as several contemporaneous news stories reported before Howe was ever taken to Tijuana for Novastem’s stem cell treatment.
In fairness, I have to acknowledge that there’s more:
A physical therapist who works with the elder Howe, Deirdre Bailey, said Thursday he showed “marked improvement” when she saw him a few days after the stem cell therapy. Previously able to stand only with extensive help, Howe could stand and walk on his own, although unsteadily and in need of close watching.
Bob Jones, a speech language pathologist who has worked with Howe over the last several weeks, said Thursday that Howe greatly improved his understanding and response to questions after the treatment. He was further improved when seen on Thursday of last week.
“He interacts more than he had before,” Jones said. “He responds appropriately to such things as proverbs, idioms similes,” when prompted to complete them. His speech, almost unintelligible before, is less difficult to understand.
So it does sound as though Gordie Howe is doing better, which is great. However, it’s not possible to tell whether this improvement is due to his stem cell infusions. Remember, just before he went to Tijuana, he had recently been hospitalized for dehydration that had rendered him unresponsive. Before that, he had had a rough November, with setbacks but overall small improvement. Indeed, if you look at the news coverage of Howe’s condition since October 26, you’ll see reports of rapid recovery mixed with reports of setbacks. It’s clearly been a bit of a rollercoaster ride, which makes it very hard to tell if any improvement is due to anything other than nature or if it’s durable. The point is simple: Given Howe’s fluctuating, but overall slowly improving condition, it’s hard to attribute his current condition to the stem cell treatment.
As hard as it is for Dr. Murray Howe to realize, as well, human beings are very prone to observational quirks. In fact, it’s clear that he doesn’t recognize it, given that the story reprints a complete e-mail by him in which he declares himself “an expert in my dad’s medical condition” and “confident that my credentials attest to my capacity to be a reliable witness.” (He also stated emphatically that he had written the entire December 19 press release announcing Howe’s “miraculous” progress since undergoing stem cell treatment.) Unfortunately, doctors are arguably among the worst when it comes to overestimating our capacities to be reliable witnesses. Unlike our unfortunately frequent view of ourselves as being objective observers, unless we make a conscious, skeptical effort not to be, we are just as prone to confirmation bias, in which observations that agree with our beliefs or hopes are more likely to be remembered and those that do not tend to be forgotten, as anyone else. Like every other human, we confuse correlation with causation.
In fact, if there’s one thing I learned from watching my mother-in-law slowly die of breast cancer six years ago, it’s that being a doctor does not inoculate one from hanging on every observation hopefully, latching hopefully onto anything that seems like an improvement, even if ephemeral or not even real, and discounting anything that looks like a turn for the worse. And that was observing a disease that is my specialty. Dr. Howe is a radiologist; he’s not a neurologist or stroke expert. Let’s just put it this way: Emotional connection plus confirmation bias do not equal a witness any more reliable than average. There’s a reason why doctors generally do not treat loved ones. Emotional attachment affects judgment a lot more than we would like to admit. Emotional attachment also makes one prone to denial. I know this from personal experience too. Indeed, I could give you a specific example from when my mother-in-law’s cancer recurred in which denial led me to a very stupid conclusion about a finding, but I’m too embarrassed about it to admit the details to any but my closest family.
But let’s say that Howe really is as much improved as has been described, which, again, would be awesome. That still doesn’t really mean that it was the stem cells that are responsible, given that he had been recently hospitalized and had had a rocky course, although it must be conceded that it might have been the stem cells. Certainly everyone seems to be assuming that it was the stem cells. For instance, the physical therapist saw him “a few days after” the treatment. When did she see him last before that? When he was in bad shape at the end of November and in early December? The same question applies to the speech therapist. Again, correlation does not necessarily equal causation. For example, on December 3, the Detroit Free Press reported:
Son Mark Howe told the Free Press that Gordie Howe has had a hard time sleeping since being hospitalized Monday. “Anxiety from dementia does that to him,” Mark Howe wrote via text. “Change of surrounding makes his dementia worse as well.”
With this in mind, it’s hard for me not to ask: How much of Howe’s improvement was due to his having been home a few days after a hospitalization from December 1 to 3 followed by a trip to Mexico a few days later, and how much was due to the stem cell treatment? It’s really not possible to say, but news accounts before Fikes’ sure gave the impression that it just had to be the stem cells. Clearly Howe’s family believes that.Stemedica and Novastem’s responses: Not reassuring
After Fikes’ story broke, I knew, in light of Stemedica and Novastem’s joint press release, that I had to update the story. Being a clinical trial guy, I was frustrated, however, that what I really wanted to know was not in either Dr. Howe’s press release, Novastem and Stemedica’s joint press release, or Mr. Fikes’ story. Here’s what I wanted to know:
Regarding the last question, I was particularly curious about this issue in light of Novastem’s policies of cash on the barrelhead for treating basically anybody, as clearly delineated on its website, the statement in Fikes’ article that patients pay for this tria, and this statement from Dr. Howe:
Did Novastem treat our father for free? You betcha. They were thrilled and honored to treat a legend. Would you charge Gordie Howe for treating him? None of his doctors ever do. I certainly am not going to criticize them for being generous.
I find it fascinating that anyone would criticize Novastem for charging, or for not charging, for their services. They appear to have developed techniques and protocols which are safe and hold promise for countless individuals. My hat is off to them for the quality service they offer.
As sympathetic as I am to the Howe family, I’m sorry. I reluctantly have to say that Murray Howe really should know better. If Gordie Howe was treated as part of a clinical trial, then Novastem should have treated him for free! That’s because if it is running a clinical trial, it should treat everyone on the trial for free. That’s the way it’s done ethically. I realize that these stem cell treatments cost something like $20,000 to $30,000 a pop, but pharmaceutical companies testing new cancer drugs, for instance, not infrequently spend way more than that per patient on clinical trials. It’s the cost of drug development. Charging patients is also one of the big issues I’ve always had with Stanislaw Burzynski, for instance, charging patients to be on his clinical trials and justifying it by saying he’s not charging them for the experimental drug (antineoplastons) but rather a “case management fee.” In fact, I would argue that it’s even more unethical if a company doing a clinical trial charges some patients for the trial but doesn’t charge others, particularly if the reason it doesn’t charge a patient like Gordie Howe is because he is a sports celebrity. What about all the rest of the peons? According to Fikes’ story, they get charged $20,000.
In trying to answer other questions, through a circuitous route I found myself in e-mail contact with Dr. Maynard Howe (no relation to Gordie Howe), the CEO of Stemedica. He was pleasant and more than eager to talk to me about Stemedica’s products, but, after some back-and-forth by e-mail, it became apparent to me that he couldn’t (or wouldn’t) provide me with any useful information about the Novastem clinical trial that I craved. Even though it had been he and Dave McGuigan, VP of Stemedica, who had reached out to the Howe family and facilitated Gordie Howe’s treatment in Tijuana, my impression was that he was basically washing his hands of the matter, referring me to Novastem for all questions because it wasn’t Stemedica’s trial. So I tried the Novastem general contact page and, ultimately, the e-mail address for the PI of this trial, Dr. Clemente Humberto Zuniga Gil, listed on his CV page on the Novastem website. I don’t know whether it was my e-mail through the general contact page, my direct e-mail to Dr. Gil, or, again in fairness, my previous communication with Maynard Howe having led him to contact Novastem that provoked a response, but on Saturday afternoon I received an e-mail response from the president of Novastem, Rafael Carrillo.
To be fair, Mr. Carrillo was pleasant and accommodating. His e-mail responses struck me as very earnest and eager to explain his company’s position, stating that he was looking into registering Novastem’s clinical trial with ClinicalTrials.gov and COFEPRIS. He even sent me a PDF file containing a rather bare bones clinical trial schema and tried to educate me about Mexican regulations governing clinical trials. Unfortunately, the information he gave me confirmed some of my misgivings about the trial and created others. For example, remember when I expressed puzzlement earlier in this post about what the clinic’s being registered with COFEPRIS meant? Well, he informed me that it meant:
As it states in our press release Clinica Santa Clarita is federally licensed to administer stem cell therapy. This means that the Mexican regulatory agency has authorized Clinica Santa Clarita and its doctors to apply stem cell therapy as the doctor sees fit. With the abundance of research across the globe and with the safety profile and high level of manufacturing Stemedica utilizes the Mexican authorities have felt it is justified to grant us a license to administer, as well as importing and banking stem cells. We treat all patients under IRB approved clinical trial protocols. We do this for two reasons, 1. We want to publish all our results. We want to share information. We believe that the more structured our data the easier it will be to publish. 2. We want to protect the patient. We have inclusion/exclusion criteria, informed consent, adverse event reporting, etc. At this point not everyone is a candidate for treatment. We want to make sure we are ethical in selecting patients for treatment.
So, in other words, the “federally licensed” part that confused me means that Clinica Santa Clarita can do pretty much anything it wants with stem cells, which is no doubt how it has been able to advertise its services and treat patients off protocol in Tijuana. Learning this actually opened my eyes greatly as to how a weak regulatory environment in Mexico allows all sorts of dubious stem cell clinics to thrive in Mexico. In fairness, it is to Mr. Carrillo’s credit that he wants to do clinical trials and ultimately publish his company’s results. However, there is a problem—several, actually. First among them, as I pointed out before, the doctors with whom he is working appear not to have the requisite background in clinical trial design or stem cell science to produce a clinical trial that will generate useful data (more on that in a moment, when I discuss the clinical trial itself). He needs experienced clinical trialists, and I just don’t see any. More problematic from an ethical standpoint is that Mr. Carrillo what was reported in Fikes’ story and tried to justify why Novastem charges patients for clinical trials:
Another issue you have brought up is payment. We are participating in patient funded research. We feel patient funded research is a viable option for both patients and doctors alike. On one hand we are not a billion dollar corporation that can fund all research, on the other hand we are following the examples of institutions such as the Mayo Clinic and MD Anderson Clinic who use this model. Patients know they have to pay. No promises are made to patients. It is very clear to all involved. We, and the IRB, feel there is enough evidence of safety and efficacy in the journals and doctor experience to proceed. Patients who choose to participate with us feel the same way. At no point do we hide this point.
In this particular trial the cost is around $30,000. Over half the cost is the cells alone, in addition to that we pay for the follow up work, the cost of patient recruitment, doctors fees, facility use fees, etc. Although $30,000 is a lot of money, to put it in perspective, it is also the cost of a knee replacement. Without being an expert in the field I believe that if this therapy proves to be effective, the cost benefit analysis will prove that getting the treatment is a good option. Also, like everything else that is new, with time and economies of scale price will go down substantially.
It was at this point that I heard disturbing echoes of Stanislaw Burzynski and his justification for charging patients tens—or even hundreds—of thousands of dollars to be on his clinical trials. It’s also a misunderstanding of how cancer centers like M.D. Anderson do things. For example, the M.D. Anderson website specifically addresses this issue, stating that “if you are participating in a clinical trial, the trial sponsor, embassy or your insurance company may cover some of the charges. Items paid by the clinical trial will be listed in your Charge Estimate Letter” and that “you or your insurance will be responsible for the charges not covered.” Generally, sponsors of the clinical trial have to cover the cost of the drug (or, in this case, biologic) and care that’s normally not part of standard of care but is related to the trial (such as additional scans or tests). Presumably, that’s how Stemedica’s trials work north of the border. Admittedly, this method leaves a big hole. Patients who don’t have health insurance will often have a huge difficulty paying for their care not related to the clinical trial and thus will have difficulties accessing cutting edge clinical trials because they can’t pay for their own regular care. Yay, USA!
But what about the trial itself?
First, according to the document supplied me, this trial underwent IRB approval on September 28. It is summarized thusly:
This is a pilot study in which a group of 30 volunteer subjects, with motor aphasia due to stroke will receive 90 x 106 of NSC intrathecally and an intravenous infusion of 90 x 106 of MSC. Leaving a window of 24 hours in between therapies. The subject follow up will continue for six months to verify safety, tolerance and to evaluate preliminary efficacy over speech, neurological function and quality of life.
This is roughly the same number of stem cells used in the Stemedica trial (one million per kg), but given intrathecal (into the cerebrospinal fluid) and intravenously. Here is a diagram of the study:
It’s a fairly basic design, with these inclusion criteria:
Regarding #4, it is known that Gordie Howe suffers from significant dementia. It is thus highly unlikely that he was able to understand and sign the informed consent, but I suppose I could be wrong about this, given that I don’t know the result of his neuropsychiatric evaluation. There’s no mention that the family can give consent for the patient; so I assume that, strictly following the protocol, they can’t. In fact, the exclusion criteria are:
This study is a not-unreasonable phase I study, although it lacks a dose escalation component, in which doses are ramped up in order to estimate the maximum safe and tolerated dose, and some important inclusion criteria (more later). Also, its endpoints aren’t well described. It’s also highly unlikely to detect any statistically significant evidence of neurologic improvement, given that there is not a strong attempt to make the group being tested more homogeneous by, for instance, setting limits on various scores. I also wonder how Novastem defines ability to understand and sign the informed consent. There’s also the issue of how cognitive deterioration is defined. Given the news reports, it could well be that Howe’s cognition was deteriorating, but, equally importantly, it could well be that he was getting a bit better. That’s where the Stemedica trial is actually better. It includes criteria requiring neurologic stability; without that, so soon after a stroke, it’s almost impossible to tell if improvement is likely due to the treatment or if it’s just improvement that was occurring as a normal part of recovery.
There’s another issue. In Fikes’ story, Dr. Murray Howe gives the following rationale for wanting to get his father on the Novastem trial ASAP, based on his having “one foot in the grave”:
However, the [Stemedica] trial requires participants to have had the stroke at least six months ago. So Howe wouldn’t qualify until late May.
Even more to the point, there was substantial doubt whether the elder Howe would survive for six months, or even until Christmas, said Murray Howe. Howe enjoys physical activity, and if unable to move he would lose his will to live.
I totally understand the Howe family’s desire to throw a “hail Mary” pass to try to save their dad (or at least make him more functional and improve his quality of life). My wife and I looked for the same thing when her mother was dying from metastatic breast cancer, which is why we had her evaluated by the phase I group at my cancer center. I’ve been on both sides. However, in designing and carrying out a clinical trial it’s critical to be very careful not to feed into the normal desires of family to do something. It’s equally important to remember that, no matter how much you repeat that “there are no guarantees” or that “this probably won’t work,” the family will latch on to the chance that it will work. That’s part of the reason why “patient-funded” clinical trials, as Mr. Carrillo describes them, are inherently prone to becoming exploitative. Just look at Stanislaw Burzynski, if you don’t believe me.
If Gordie how really was deteriorating so rapidly four weeks ago that there was substantial doubt about whether he would survive until the end of the year, then he probably should not have been a candidate for any clinical trial for stroke. Indeed, most clinical trials for chronic conditions like stroke (and even cancer) exclude patients who are deteriorating so rapidly because they are incredibly unlikely to benefit and they make it hard to detect a real benefit if there is one. Indeed, notice how the Stemedica trial has an inclusion criteria of “life expectancy greater than 12 months.” In marked contrast, there is no equivalent inclusion criterion in the Novastem trial, which is a huge gap.
Finally, the Novastem clinical trial is designed to examine the effects of stem cells on aphasia. A man who suffers from, if news reports are to be believed, significant dementia and, if Murray Howe’s account of his father’s condition in early December is accurate (and I have no reason to doubt it), and Gordie Howe truly had “one foot in the grave” to the point where his son Murray didn’t think he could wait “even 30 days for a Compassionate IND treatment in the United States,” then he was not a good candidate for a clinical trial—any clinical trial, although an expanded use IND might still have been appropriate, particularly given that reports in early December from Howe’s other son Mark described him as “doing better overall than he was several weeks ago when he had a massive stroke” and that he had “improved enough in the past 24 hours to where we expect him to be out of the hospital and in his own bed at home before the night is over.”Hope vs science vs exploitation
In clinical trials of new therapies, particularly for conditions that are either currently irreversible and result in a greatly diminished quality of life (like a stroke) or that will ultimately kill the patient (like certain cancers), it is always difficult to balance rigorous science versus hope and wanting to help as many patients as possible. After all, hope is part of why such patients enroll in clinical trials; that cannot be denied, and good clinical trialists are acutely aware of this. However, the ethical researcher tempers that hope and tries to keep it from being unrealistic. Moreover, as the example of my own experience with my mother-in-law’s stage IV breast cancer and the writings of Dr. Murray Howe about his father show, being a physician does not inoculate one from unrealistic hope and human cognitive shortcomings like confirmation bias. As physicians, we find this hard to admit to ourselves, but it’s true.
Similarly, it is potentially exploitative to require patients to pay to be on a clinical trial. That’s why legitimate trials in the US don’t require it, except in very uncommon, highly defined situations, and even then it is generally frowned upon. It is also highly unethical to treat patients on clinical trials differently based on their status. Ideally, none should pay to be on a trial, but if patients are being made to pay then it is, in my opinion, breathtakingly unethical to excuse one patient from paying just because he is a famous sports icon. It’s more unethical when that patient is used for publicity, as Gordie Howe has been. Such a special financial arrangement is inherently unfair to other subjects on the trial. Worse, it also smacks of paying a clinical trial subject for an endorsement and is thus potentially coercive. It is profoundly disappointing to me that neither Mr. Carrillo, Dr. Maynard Howe, nor Dr. Murray Howe appears to grasp this. Indeed, Murray Howe dismisses such concerns by writing that there were “no strings attached to their [Stemedica and Novastem's] offer” and that they “never have asked us to share Mr. Hockey’s amazing response.” Assuming that’s so, unfortunately the lack of explicit “strings attached” or explicit requests to publicly share Howe’s response doesn’t make the arrangement any less unethical or potentially coercive. Indeed, Howe points out that he shared his father’s response out of a sense of obligation, which is exactly what such arrangements engender and why they are unethical!
The saga of Gordie Howe’s stroke and his treatment at Novastem is a textbook example of why clinics like Clinica Santa Clarita are a major problem. Accountability is minimal to zero, and patients pay for experimental treatment. Unlike the case with Dr. Burzynski, I actually think that the leadership of Stemedica and Novastem believes in the Stemedica stem cell treatment. However, it is very difficult now, knowing what I know, not to walk away with the impression that Novastem was a tempting way for Stemedica to sidestep the regulations of the US and that Stemedica, its leadership apparently believing in a stem cell miracle, yielded to that temptation. Meanwhile, Mr. Carrillo seems to want to do the right thing but appears not to understand what the right thing is—or to have any clinical trialists working for him who can tell him what the right thing is.
Perhaps the saddest thing to me is that Dr. Murray Howe feels sorry for “anyone who finds this miracle ‘troubling.’” Presumably he means skeptics like Dr. Knoepfler and myself who have publicly questioned the news reports. I can assure Dr. Howe that I do not find Mr. Hockey’s progress and recovery “troubling.” No one, least of all myself, begrudges the Howe family hope. Indeed, I really do hope that Howe is doing better. I even hope it was the stem cells! After all, I’m not as young as I used to be. Cardiovascular disease runs in my family. I could easily find myself in Howe’s situation 20 or 30 years from now. I would love it if there was an effective treatment for brain damage due to stroke, and I do believe that stem cells have great potential to treat conditions that were previously untreatable.
Unfortunately, it’s everything else about his story that I find troubling, particularly how it was announced in the media, leading to numerous credulous reports portraying Stemedica’s stem cell treatments as some sort of miracle cure for Mr. Hockey and how Howe’s story as related by his family came across as very much of a piece with alternative medicine cancer cures and cures for other conditions. There is a right way and a wrong way to test treatments like this. Novastem looks as though it is taking the wrong way, whatever the motives of its president. I felt obligated to point that out because not every stroke patient is Gordie Howe.
I’m cheating. No, I’m recycling. ‘Tis the season to have to no time to get anything done. Since I know none of you pay attention to the blog of at the Society for Science-Based Medicine and I have no time with work and the holidays to come up with new material, I am going to collect and expand on the entries on acupuncture I wrote from SfSBM. Anything I write really is worth reading twice. I really need to make my multiple personality disorder work for me, but the Goth cowgirl persona is a luddite at best, so you are stuck with the over -extended ID doctor. Here goes.
‘Works” is different from having an effect, even a beneficial effect. Positive interactions between a patient and a health care provider, even when offering a pseudo-medicine, will make some patients feel better about their disease. I compare these pseudo-medicines, like acupuncture, to beer goggles. They change perception but not reality.
While changing the perception of disease for the better is of benefit, it is just not ethical to base treatment on the lie that acupuncture ‘works’.
What happens with a process like acupuncture to alter patients’ perception? It doesn’t matter where the needles are placed or even if needles are used; twirled toothpicks are just as effective as ‘real’ acupuncture, what ever that may be. What matters most for efficacy is if the patient thinks they are getting acupuncture and if they believe acupuncture is effective. Then acupuncture will have a salubrious effect on subjective endpoints. That’s it. So what is going on?
Another hint as to the mechanism of acupuncture is found in “When pain is not only pain: Inserting needles into the body evokes distinct reward-related brain responses in the context of a treatment.“
In this study, 24 people received three identical stimuli: tactile, acupuncture, or pain stimuli. There were two groups to receive the three stimuli, an acupuncture treatment (AT) group and an acupuncture stimulation (AS) group. What differed is what they were told before the stimuli:
…participants in the AS group were primed to consider the acupuncture as a painful stimulus, whereas the participants in the AT group were told that the acupuncture was part of therapeutic treatment.
They had an fMRI (who doesn’t) and a questionnaire about their subjective experience:
Behavioral results generally revealed no differences between the AT and AS groups. The questionnaire results confirmed that there were no significant differences in expectancies, fear, or anticipation and subjective pain ratings related to needles being inserted into the body between patients in the AT and AS groups.
They found no analgesic effect in the acupuncture group. But there was a difference in the fMRI (for what that is worth):
We found that reward-related regions (specifically, the ventral striatum) of the brain were activated by acupuncture stimulation and that in response to painful simulation, activity in pain-processing regions(the SII and DLPFC) was decreased only when participants were told that acupuncture needles were a therapeutic tool.
As greater activation of the ventral striatum is generally correlated with more expectations of pleasure and rewards, our results could be interpreted to suggest that acupuncture stimulation was associated with the expectation of a reward – possibly an analgesic effect – for patients experiencing acupuncture in the context of a treatment (AT group).
So depending on the context, people process the same stimulus differently. A needle that is thought to be for therapeutic acupuncture is different than the exact same needle thought to be used for painful stimulation.
Maybe. It is a small study and fMRI’s have issues as we know from dead salmon. But taken in the context of the literature pointing to the predominantly positive subjective effects of pseudo-medicines it is curious finding. Maybe not beer goggles; probably more like making wine taste better by giving it a higher price.
Acupuncture needs belief to work
Well not really acupuncture, at least not as the ancient Chinese did it. I do not think they had electricity to apply to the needles. But this was an interesting study, “Expectancy in Real and Sham Electroacupuncture: Does Believing Make It So?”
They took patients with joint pain due to aromatase inhibitors being used to treat breast cancer. The patients had either sham electroacupuncture (no current applied), electroacupuncture, or a wait-list control group, only about 20 in each group.
No surprise, those who had an intervention, be it sham or electoacupncture, had more pain relief than the wait-list control. An intervention, even if worthless, usually changes the subjective complaint for the better.
But here is where it gets interesting. They used the Acupuncture Expectancy Score (AES), a measure of how much the patient thought acupuncture would help their problem.
Over all, the higher the AES score, the better the pain response:
Each point increase in Baseline expectancy in the SA group is significantly associated with a greater percent pain reduction at Week 8 (regression coefficient = 7.9, SE= 2.8, P = .007).
In the sham group those with a high AES also had a better pain response. What is also interesting is that in the sham group there was no increase in the AES score over time and the decrease in the pain was constant.
Some in the electroacupuncture group increased their AES score with time and with a concomitant decrease in pain. Those who maintained a low AES scores had a pain response that was unchanged over time.
What they do not mention, which is a flaw, is whether blinding was effective. A little current across an acupuncture needle could easily be noticed by some of the patients and might have affected their perception of the intervention.
They say in the discussion:
Expecting a positive outcome (expectancy) at the beginning of the trial was associated with the response to SA. In contrast, patients who responded to EA had increased expectancy over the course of their acupuncture treatment as compared with nonresponders, suggesting that positive responses during the process of EA increased the expectations of positive outcomes. Our findings imply that distinct mechanisms underlie the apparently similar clinical effect of EA and SA. These findings have important implications for acupuncture and pain research as well as for clinical practice.
It may be the responders to electroacupuncture were the ones who noticed a tingling from the current and responded accordingly. Electroacupuncture is just a TENS unit tarted up with Traditional Chinese Pseudo-Medicine and this study has no implications for acupuncture except to reinforce its mechanism as an elaborate placebo.
I will mention here that I had always been taught that TENS was a legitimate form of pain relief. A quick review suggests TENS may be nothing but a placebo as well. Since more elaborate placebos yield better responses, it may be that those with the increased AES score were also those who knew they were getting TENS, a more elaborate placebo.
I wish they had tested for effectiveness of blinding, it would have been a nice addition to understanding what happened in evaluating two different placebos.
The authors say in the introduction that:
Although the response to SA has led skeptics to consider the acupuncture effect no more than placebo
And conclude with:
Our findings suggest that distinct mechanisms exist between SA and EA and challenge the notion that acupuncture is “all placebo.”
Methinks you doth protest too much. I see the study has variations of placebo effect, all placebo and nothing but placebo.
There were four kinds of beer goggles evaluated in this study; sham acupuncture with low or high AES and electroacupuncture with low or high AES with the added potential confounder that some in the high AES group may have known what they were getting TENS. The increasing AES and subsequent improved pain response may be no more than the effects of a more elaborate placebo with a positive feedback loop.
To my mind this is more data to support the notion that the effects of acupuncture, like the effects of all of CAM, is simply the patient deciding they are getting better, the pseudo-medical equivalent of kissing a boo boo to make it feel all better.Animal torture
Psychology was, I admit, not my strong suit back in my pre-med days, the one class that ruined an otherwise-exemplary report card.
The only thing I took away from my psychology class was the concept of learned helplessness, perhaps because that describes a lot of medical education. To quote the ever-helpful Wikipedia:
Learned helplessness is a behaviour in which an organism forced to endure aversive, painful or otherwise unpleasant stimuli, becomes unable or unwilling to avoid subsequent encounters with those stimuli, even if they are escapable. Presumably, the organism has learned that it cannot control the situation and therefore does not take action to avoid the negative stimulus.
Put a dog in a box, shock it, and it gets depressed and stops looking for an escape. I think of learned helplessness when I see someone abusing an animal by jabbing it with useless needles (aka acupuncture). I know it is projection, but every time I see pictures of animals getting acupuncture, I see a depressed animal with learned helplessness.
Do any of these poor animals look happy with their acupuncture? Not to my eye.
The most recent animal to undergo well intentioned, and we know what the road to hell is paved with, torture, are Spanish owls.
1,200 injured owls are brought every year to a hospital in Spain where, for the last 6 years, then have been tortured with needles once a week for 10 weeks. Although they brag that 70% survive, I wonder if the added stress helped to kill the remaining 30%. Ten weeks of weekly torture cannot be good for wild owls. More likely they are improving in spite of the acupuncture rather than because of the acupuncture and given the lack of gloves with the punctures, I wonder how many died of inadvertent infections.
They give the usual nonsensical reason for using acupuncture and the usual denial of harm:
It stimulates self-curing mechanisms in the organism. It does not cause side-effects…
Don’t you think before you inflict pseudo-medicine on animals you would want to do a study not only to show efficacy, but to prove that you are not killing the animals with the added stress? I would. That is the nice things about animals: they are unable to complain about the numerous complications of acupuncture and so the practitioner can delude themselves as to the safety of their torture.
Poor owls. I am not a PETA kind of guy, but I am sympathetic to all the animals needlessly abused with completely worthless ‘therapeutic’ and experimental acupuncture.After the fact rebuttal
I spent 5 days wandering the NE: Boston, Newport, Plymouth, back to Boston, Salem and then home. I was invited to give a talk on influenza and participate in a panel discussion about low back pain. The panel consisted predominantly of those who take care of backs for a living and I felt a bit like an Alzheimer’s patient who wandered into the room by mistake.
The panel was asked about using pseudo-medicines and as one of the militant members of the science-based medicine community, I gave my best three-minute summary on which SCAMs are useless. Then one of the members of the audience made a comment that, due to time constraints, I was unable to respond to.
So here is a paraphrase of the comment, and my response.
He started by saying he was a big believer in science-based medicine but…
But. Beware the but. That often means the speaker is about to endorse some bit of pseudo-medicine that he thinks deserves our consideration because, hey, I use it and it works for me. I was not disappointed.
He continued, mentioning that he has treated plantar fasciitis for years, usually with a single needle, often with only one or two treatments and it works more often than not.
This is, I suspect, the greatest reason that pseudo-medicines continue to thrive.
First is relying on experience as a valid criterion for deciding on a therapeutic intervention. Experience makes us better health care workers in so many mays it is virtually impossible for HCWs to recognize that the three most dangerous words in medicine are not “I lack insurance” but “In my experience.” They are a powerful meme for the speaker and totally useless to the listener.
Variations of the concept are found in the ideas that:
the plural of anecdote is anecdotes, not data
And the Richard Feynman quote:
The first principle is that you must not fool yourself–and you are the easiest person to fool. So you have to be very careful about that. After you’ve not fooled yourself, it’s easy not to fool other scientists. You just have to be honest in a conventional way after that.
The problem is that Dunning-Kruger appears to be the default mode for most health care workers, the
cognitive bias in which unskilled people make poor decisions and reach erroneous conclusions, but their incompetence denies them the metacognitive ability to recognize their mistakes.
So to my mind the speaker personified what may be the primary issue with pseudo-medicines in health care: the reliance on experience and the inability to recognize that it is useless.
He concluded with the usual chestnut about not throwing out the baby with the bath water. I hate that cliché.
Me? When it comes to pseudo-medicine I would throw out the baby, the bath water, the tub, the soap, the shampoo, the washcloth and the towel.Lipstick on a pig?
I was wandering the Oxford English Dictionary and found a new definition for worthless: “Noun. A clinical efficacy trial with no blinding, no placebo, and only subjective endpoints derived from patient self-reporting.”
The OED is a stickler for examples of usage, so they pointed to “Effect of Perineal Self-Acupressure on Constipation: A Randomized Controlled Trial” in the Journal of General Internal Medicine. The study is out of UCLA, Yale and the Southwestern Law School !?!
They compared usual care or perineal acupressure for constipation. Perineal acupressure. Where did perineal acupuncture come from? I don’t know. The introduction has a discussion on the potential benefits of perineal massage and pressure, which can alter perineal muscles, increase rectal tone (wouldn’t that increase constipation?) and perhaps aid in defecation.
Then they jump to testing:
perineal self-acupressure, which consists of a patient repeatedly applying external pressure to the perineum.
Why acupressure? Why the acu? They make no mention of meridians or chi, which suits me fine.
There is an acupoint in the perineum in Traditional Chinese Pseudo-Medicine and it is not used for constipation, but rather it regulates yin:
The perineal points have nothing to do with constipation. So why the acu? Because tarting up a lousy study with pseudo-medicine gives the results more cachet and press than it deserves? That is my theory.
This is not an isolated example. A study adds ‘acu’ and now it gets far more attention than one that doesn’t. We saw this with “Dopamine mediates vagal modulation of the immune system by electroacupuncture.”
Virtually anything can get the acu designation if desired, and then more attention. I give antibiotics through acupuncture IV’s. Much cooler than regular IV’s. I can publish a study on my outcomes for cellulitis using acupuncture IV’s. I’ll tell half the patients they are getting acupuncture IV’s and half will get standard IV’s. I predict better satisfaction in the acupuncture IV cohort.
Maybe we jump on the bandwagon as well to get more press: Acu-Science-Acu-Based Acu-Medicine?Bad studies lead to wasting money
It is amazing how quickly a single study can lead to an analysis as to whether an intervention should be used because it is cost effective.
There is no reason that acupuncture, a complicated magical ritual, should have any specific effect on any pathologic process. However, when I watch videos of acupuncture the process looks quite nice, except, of course, for the whole needles being stuck in the skin with zero attention to infection control. Relaxing in a caring and supportive environment cannot help but make people feel better, as long as they do not get hepatitis B or MRSA.
Like all interventions that do nothing, acupuncture is indicated for virtually everything (except as a form of contraception), at least by their proponents. Depression is on the list of processes that are not effectively treated by acupuncture.
After reviewing thirty, count ‘em thirty, studies, with 2,812 patients, the last Cochrane review:
found insufficient evidence to recommend the use of acupuncture for people with depression.
One would think that when 30 studies demonstrate an intervention with no basis in reality is useless, no self-respecting IRB could ethically approve the 31st study. Nope. In 2013 there was yet another study, “Acupuncture and Counselling for Depression in Primary Care: A Randomised Controlled Trial“, that demonstrated that counseling and acupuncture were associated with the same degree of reduction in depression at three months.
With no wait list and no sham acupuncture control there can be zero conclusions made about whether or not acupuncture per se (as opposed to the magical ritual) was of benefit or whether it was the natural history of the depression in that population.
The authors call it:
A pragmatic trial asks whether the intervention works under real-life conditions.
While I would call the trial a waste of time and money, whose methodological flaws ensure it proves nothing. Again, isn’t part of the ethical and practical considerations of IRB’s to avoid studies that are methodologically garbage? Guess not.
The article states no conflicts of interest, which I am sure is true technically i.e. financially, but when the lead author of a study suggesting magic helps depression is
previously trained as a practitioner of acupuncture and Chinese herbal medicine and subsequently founded the Northern College of Acupuncture
I remember the ever-so-wise words:
Conflicts of interest are very common in biomedical research, and typically they are inadequately and sparsely reported. Prejudice may not necessarily have financial roots. Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings.
I will mention as an aside that PLOS does not publish author titles (Lac, ND, MD) in their papers. If a pseudo-medicine is being evaluated it would be nice to know which kind of pseudo-medical provider is doing the evaluation. As the old saying goes, “Go to Midas, get a muffler.”
So we have a preponderance of literature that demonstrates acupuncture is useless for depression and a fatally-flawed study that proposes an efficacy that doesn’t exist. What to do next? Not go to Disneyland.
You are a proponent of acupuncture. You have just finished a methodologically-horrible study that you can spin into demonstrating acupuncture is helpful for depression despite a vast contradictory literature. You note that:
Acupuncture is rarely provided within the UK’s mental health service or primary care, but private provision of acupuncture for depression is not uncommon.
Although what constitutes “not uncommon” from the reference is vague. In a table, 7% of providers use acupuncture for “psychological” disorders and the only mention of depression in the text is:
Anxiety, stress and depression were the three most prevalent psychological complaints and more commonly treated by independent acupuncturists.
In what looks like a manipulation of PLOS as part of a marketing program to increase the use of acupuncture in England, most of the same authors of the original paper hired an economist who found that, hey, acupuncture is cost effective.
If I had a conspiratorial bent, I would point to this as proof that the medical literature is being manipulated to further the financial gain of Big Pseudo-Medicine.
But it is not.
Just another sad example of the failure of peer review when applied to pseudo-medicine.Bad infection control
In a prior entry I have mentioned my visual Googlewhack: I could find only one picture of gloves being used during acupuncture, and it was not being performed by an acupuncturist but a physical therapist doing dry needling.
I have also discussed the recalcitrance to basic infection control that informs the practice of acupuncture. It gives me the willies to watch acupuncture videos. It often looks as if they are trying to spread contagion with their technique.
Up north in British Columbia an acupuncture clinic was closed because of poor
infection prevention and control standards (that) poses a health hazard to clients.
That defines all the acupuncture I have witnessed.
Based on the investigation of the centre, we are alerting clients of Ms. Hu that they may be at increased risk of exposure to blood-borne infections that can be transmitted by improper and unsanitary acupuncture techniques.
The article alludes to acupuncture as the source of infections as well as:
other treatments involving blood or bodily fluids.
How many people were exposed is not certain as:
Murti said Hu did not keep proper records, and it’s difficult to know how many people might have been affected.
But it is more than 1,000 people. Take that, Typhoid Mary. The health department is recommending testing by clients for blood-borne pathogens. Normally I would worry about HIV and Hepatitis B and C, but evidently Hu had even worse technique than I would have thought possible.
On her door is a list of diseases for which she wants her clients to contact her if they have been exposed to or currently have so she can make a special appointment.
The diseases include smallpox. Smallpox.
Yes, if you have or have been exposed to smallpox, most certainly see Hu for acupuncture, or perhaps other treatments involving blood or bodily fluids.
This list is a further suggestion that infection control is not well understood in the acupuncture world.Cupping
We only have one big time professional sports team in Portland, the Trailblazers. No football or baseball. We do have professional soccer, but that doesn’t really count. In Portland the Blazers rule.
I had long thought cupping in athletics was a protective device to prevent groin injuries, although it is evidently voluntary in the NBA, as some have learned to their discomfort.
I think protective cupping would be a good idea. Therapeutic? Not so much. Evidently promoted by their Director of Player Health and Performance, cupping is a form of pseudo-scientific nonsense that is being used by the Blazers. I have discussed one form, moxibustion, before. Like most pseudo-medicine, it is an elaborate placebo with no real effects on real disease.
Its alleged mechanism of action is:
the idea is the suction draws fluid out of the area, Kaman explained, allowing tissues to heal more quickly.
And is not based on known processes. It is more akin to the wet sock treatment for stuffy nose, divorced from anatomy and physiology.
I am not surprised the Blazers are using it, since athletes often use pseudo-science. I suspect golfers lead the list. I still had to laugh at one quote:
“It’s scientific stuff,” Kaman said. “I could sit here and talk to you about it, but you wouldn’t know what I was talking about. I’m not calling you dumb it’s just a mixture of Western and Eastern medicines and some people think it works, some people don’t.
It is not scientific stuff, it is pseudo-scientific stuff. That is why no one understands what you are talking about. The theory and practice behind cupping is gibberish. Those who think cupping does not work are probably those who understand reality. As one meta-analysis said:
Although RCTs provide a higher quality of evidence, we included non-RCTs in this study because the limited number of RCTs did not provide convincing evidence.
Demonstrating the usual results of alternative medical studies: it only has effects when the studies are poorly done. The most unreliable form of evidence is the anecdote:
“I find it works pretty good,” Kaman said and “It works,” Batum said.
Well, it doesn’t in any well done study. Any positive results are due to placebo effects, the medical beer goggles.
I wonder if the Blazers will suggest giant magnets (3:52 mark) next for player injuries?