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Clinical equipoise versus scientific rigor in cancer clinical trials

A critical aspect of both evidence-based medicine (EBM) and science-based medicine (SBM) is the randomized clinical trial. Ideally, particularly for conditions with a large subjective component in symptomatology, the trial should be randomized, double-blind, and placebo-controlled. As Kimball Atwood pointed out just last week, in EBM, scientific prior probability tends to be discounted while in SBM it is not, particularly for therapies that are wildly improbable strictly on the basis of basic science, but for both the randomized clinical trial remains, in essence, where the “rubber hits the road,” so to speak. Indeed, when the prior probability of a therapy working based on preclinical basic science investigations appears high, EBM and SBM should be (and are, for the most part) more or less indistinguishable.

The ethics of clinical trials, however, demand a characteristic known as clinical equipoise. Stated briefly, for purposes of clinical trials, clinical equipoise demands that at the time a clinical trial is being carried out there be a state of genuine scientific uncertainty in the medical community over which of the drugs or treatments being tested is more efficacious and safer. One reason (among many) why the Gonzalez trial was completely unethical was a lack of clinical equipose. (Lack of adequate informed consent was another.) Lack of clinical equipoise is also the reason why a prospective randomized, double-blind, placebo-controlled clinical trial testing an unvaccinated group versus a vaccinated control group to determine whether vaccines cause autism would be completely unethical. Such a trial would egregiously violate the principle of clinical equipoise because the unvaccinated group would be left unprotected against potentially life-threatening vaccine-preventable diseases, and that is completely unacceptable from an ethical perspective. Consequently, we have had to rely on on the accumulation of data from less rigorous trial designs to demonstrate that there is no correlation between vaccines and autism. Even so, the accumulated weight of such evidence is enough, and for some questions that is the best we can do because scientific rigor sometimes conflicts with human subjects research ethics. This is an extreme example of lack of clinical equipoise, but it illustrates the point. If we know (or have good scientific reason to suspect) that one treatment is better than another, it is unethical to randomize patients to the arm that receives what is, based on what is known at the time of the trial, likely to be an inferior treatment.

Sometimes, however, the question of whether clinical equipoise exists in a clinical trial is not so obvious as it is for trials proposed by cranks. This situation sometimes crops up in clinical trials for cancer. I was reminded of this issue by a front page story in the New York Times yesterday, New Drugs Stir Debate on Basic Rules of Clinical Trials. In it, reporter Amy Harmon uses a classic human interest story to highlight the issue of clinical equipoise in a clinical trial for a new drug for melanoma that shows great promise. In brief, it is the story of two cousins, one of whom is receiving the new “wonder drug” (whether it is truly a wonder drug or not remains to be seen) in a clinical trial and one of whom is receiving the current standard of care for stage IV melanoma, which, to put it bluntly, sucks in that it has very little effect in prolonging life:
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Posted in: Cancer, Clinical Trials, Medical Ethics

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Using attacks on science by the anti-vaccine movement as a “teachable moment”

Last week, I wrote one of my usual ridiculously detailed posts analyzing a recent study (Price et al) that, if science and reason ruled, would be the last nail in the coffin of the hypothesis connecting autism with the mercury-containing preservative, thimerosal, which used to be in many childhood vaccines but was phased out beginning in 1999 and disappearing in infant vaccines except for the flu vaccine by early 2002. Of course, for at least the last five years, the thimerosal-autism hypothesis has been a notion whose coffin already had so many nails pounded into it that Price et al probably had a hard time finding even a tiny area of virgin wood into which to pound even a tiny nail of a study published in an impact factor one journal, much less the spike that their study in Pediatrics represented.

Unfortunately, as we know, in the anti-vaccine movement unreason rules, and, not unexpectedly, as a result this study has changed little in the debate, the fortuitously ironic happenstance of its being released the day before Mark Blaxill and Dan Olmsted’s anti-mercury screed Age of Autism not withstanding. To physicians and scientists, it is another strong piece of data being added to the confluence of evidence that has shown no link between mercury in vaccines and autism (or vaccines themselves and autism, for that matter). It is yet another confirmation that vaccines are safe. In contrast, to the anti-vaccine movement, it is simply yet another confirmation that the CDC is hopelessly biased, that scientists are in on a conspiracy to suppress The Truth, and that they are the poor persecuted minority, the only ones who know What Is Really Going On.

When I wrote my post last week, I didn’t know whether or not it would be worth my while to comment on the response of anti-vaccine activists to the study. The reason is that, as fun as it is to reveal their responses to be as vacuous as they are, I wasn’t sure that it would be educational. Granted, sometimes educational value takes a back seat to criticism, but sometimes it’s just too easy. In any case, by mid-week, there had been virtually no criticism of the study yet from the usual sources; so I figured it to be a moot point whether or not I would end up writing about this study one last time. Then, on Thursday morning I noted an e-mail in my in box. In order to keep my finger on the pulse of various pseudoscience movements, I subscribe to e-mail lists of various crank organizations, one of which is Generation Rescue and another of which is SafeMinds. SafeMinds, as you may recall, is the organization headed up by Sallie Bernard. As you may also recall, Bernard was originally on the external consulting committee that participated in the design of Price et al, and, before it, Thompson et al, the two of which ultimately made up a one-two punch against the mercury-autism hypothesis. When she saw that the results of Thompson et al were going against her idea and that no link between thimerosal-containing vaccines and neurodevelopmental disorders was showing up in the preliminary analyses, she resigned from the committee and started attacking Thompson et al. What surprised me was that she wasn’t ready with a criticism of Price et al when it was released.
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Posted in: Clinical Trials, Vaccines

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The final nail in the mercury-autism hypothesis?

PROLOGUE: BAD LUCK AND BAD TIMING

Two and a half years ago, very early in the history of this blog, I wrote one of my usual logorrheic (although I prefer the word “comprehensive”) posts entitled Mercury in vaccines as a cause of autism and autism spectrum disorders (ASDs): A failed hypothesis. In that post, I characterized the scientifically discredited notion that the mercury in the thimerosal preservative that used to be in several childhood vaccines was the cause of the “autism epidemic” as “one of the most pernicious medical myths of recent years.” And so it is. I like to characterize the notion that thimerosal-containing vaccines (TCVs) cause autism as the American version of the British myth, popularized by Andrew Wakefield and a sensationalistic British press, that the measles-mumps-rubella (MMR) vaccine causes autism and “autistic enterocolitis.”

Both notions were based on confusing correlation with causation, aided and abetted by some truly bad science, and both notions have been painfully difficult to dislodge. Indeed, in the case of Wakefield, only now that Wakefield was stripped of his license to practice in the U.K. by its General Medical Council, leading to The Lancet finally doing what it should have done six years ago and retracting Wakefield’s 1998 study that sparked the MMR frenzy in the U.K. and arguably kickstarted the modern anti-vaccine movement, do I sense that journalists are finally “getting” that science does not support the idea that the MMR vaccine causes autism. Andrew Wakefield may be trying to fight back with his book Callous Disregard after his disgrace was complete, basking in the glow of admiration of die-hard anti-vaccine groups, but, for now, at least, Wakefield and his MMR fear mongering are yesterday’s news, and that’s a very good thing indeed–at least for as long as it lasts.

Perhaps it is the fall of Andy Wakefield that has led to an apparent resurgence of the concept that mercury in TCVs somehow causes autism, after having faded into the background after the CDC and AAP recommended that thimerosal be removed from all childhood vaccines in 1999 and the last TCV having expired towards the end of 2001. After all, if the hypothesis that TCVs cause autism had been correct, we should have expected to see a marked decrease in the incidence of autism and autism spectrum disorders (ASDs) within about 5 years of 2002, given that the vast majority of cases of ASDs are diagnosed between the ages of 2 and 5. We have not, and, even though its adherents have kept moving the goalposts back regarding the date that we should start to see a leveling off and drop in the incidence of ASDs, starting with 2005, then 2007, and now, apparently, 2011 (which is only less than four months away, by the way), even Jenny McCarthy’s anti-vaccine organization originally founded by J.B. Handley and his wife, namely Generation Rescue, began demphasizing mercury in 2007, after having stated flatly on its website that autism is a “misdiagnosis for mercury poisoning” for so long. Since then, “too many, too soon” has been the favored propaganda talking point.

Of course, not every crank is ready to abandon the myth that TCVs cause autism. Indeed, tomorrow two mercury militia “heavy hitters” and bloggers for the anti-vaccine propaganda blog Age of Autism, Mark Blaxill and Dan Olmsted, will be releasing a book entitled Age of Autism: Mercury, Medicine, and a Manmade Epidemic. In anticipation, four weeks ago I actually e-mailed the publicist to send me a review copy of Age of Autism. I have yet to receive the book. I wonder why. Be that as it may, it amuses me that the official release of the release of the not-so-dynamic duo of the mercury militia’s book actually will one day after a study that is arguably the last nail in the coffin of the very dead hypothesis that TCVs cause autism was released. Either the great pharma conspiracy is far more conniving and effective than even J.B. Handley thinks, or Blaxill and Olmsted’s luck is just that bad. As I anticipate the conspiracy mongering posts about this bad timing aside, let’s just take a look at this last coffin nail, which is a study by Price et al that was released today in the journal Pediatrics entitled Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism.
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Posted in: Neuroscience/Mental Health, Vaccines

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Mike Adams on Dr. Mehmet Oz’s colon polyps: “Spontaneous” disease?

Given that it’s a holiday and I debated whether or not I even wanted to post anything today, I think I’ll keep things light and uncharacteristically brief today. After all, not every post can be like last week’s epic on Avastin or the week before’s epic on peer review. That’s a lot of work, and it is a holiday, after all. Besides, sometimes a perverse mood overtakes me, and I feel the need to go slumming.

Bring on Mike Adams.

Mike Adams, as regular readers may know, runs the website NaturalNews.com from deep in the jungles of Ecuador. His website is a one-stop shop, a repository if you will, of virtually every quackery known to humankind, all slathered with a heaping, helping of unrelenting hostility to science-based medicine and science in general. True, Mike Adams is not as big as, say, Joe Mercola, whose website, as far as I can tell, appears to draw more traffic than NaturalNews.com, but what Adams lacks in fame he makes up for in sheer crazy. If you don’t believe me, check out his latest hip-hop video Vaccine Zombie:

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Personally, if I had anything to do with the Michael Jackson estate, I’d be suing for copyright infringement. Still, grudgingly, I have to admit that the animation is pretty good, although when Mike Adams raps, “‘Cause livin’ without a brain ain’t half bad,” I don’t think he realizes that he is apparently living proof of that. In fact, so full of crazy is Mike Adams, that there has even been disagreement among SBM bloggers over whether we should lower ourselves to deal with some of his loonier stuff. Guess which side I took?

The reason I argue that, even at the risk of wrestling the proverbial pig in mud, we should not shy away from taking on some of Mike Adams’ lunacy from time to time is because he illustrates certain aspects of the mindset that allows unscientific so-called “alternative” medicine to remain popular. Sometimes, articles on Adams’ website bring up the question of whether Adams really believes the utter nonsense he lays down or whether he is simply a scammer, much like Kevin Trudeau is a scammer, and doesn’t believe a word of it but has such contempt for his followers that he thinks nothing of lying to them to sell them whatever nostrums he’s hawking on his website. You’ll see what I mean in a minute. I hope.

On Friday, Adams decided to attack “America’s doctor” and a promoter of woo whom we have from time to time taken on here at SBM, Dr. Mehmet Oz because, of all things, Dr. Oz apparently underwent colonoscopy and was found to have a precancerous polyp. That this might have happened to him is not at all surprising given that Dr. Oz recently turned 50 and current guidelines recommend commencing screening by colonoscopy at age 50. Indeed, I’m only a couple of years from needing to submit to the same screening myself. In any case, Adams decided to write one of his patented screeds, entitled, Dr. Oz colon polyps raises question of “spontaneous disease” without cause. In it, he inadvertently reveals a lot about alt-med thinking, making it worth a brief discussion.

Adams starts out:
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Posted in: Cancer, Health Fraud

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Avastin and metastatic breast cancer: When science-based medicine collides with FDA regulation

One of the most frustrating aspects of taking care of cancer patients is that in general, with only a few specific exceptions, we do not have good curative therapies for patients with stage IV cancer, particularly solid tumors. Consequently, patients with stage IV disease are viewed as “incurable” because, the vast majority of the time, they are incurable. Over the years, we have thrown everything but the kitchen sink at patients with stage IV disease, largely with dissapointing results. That’s not to say that the few specific exceptions to which I alluded are not a reason for hope. After all, patients with colorectal cancer and liver metastases used to have a median survival of around 6 months, but these days, with newer chemotherapeutic regimens like FOLFOX plus Avastin, median survival has more than tripled. While expecting to live less than two years is cold comfort to cancer patients with this particular clinical situation, the prognosis is far better than it was.

Of course, I specifically mentioned Avastin because it’s been in the news a lot recently with respect to my area of clinical specialty, breast cancer. Specifically, beginning in July there started appearing a spate of stories about the FDA considering revoking the approval of Avastin for advanced breast cancer based on recent studies that demonstrate that it does not prolong survival in these patients. Many lay people and patients find this reconsideration of Avastin to be quite puzzling, given that the drug was granted accelerated approval in 2008 and has since gone on to be used fairly widely. Given that the case of Avastin in breast cancer is rapidly becoming a classic case study of how messy science-based medicine can be when practiced in the public eye and debated among pharmaceutical companies, the government, and patient advocacy groups.
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Posted in: Cancer, Clinical Trials, Pharmaceuticals, Politics and Regulation

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Tai chi and fibromyalgia in the New England Journal of Medicine: An “alternative” frame succeeds

It never seems to fail. I go away for a few days, in this case to combine fun with pleasure and pleasure with fun by giving a talk to the Chicago Skeptics and at the same time meeting my brand new (well, by this time three weeks old) nephew for the first time, and something always happens. Before I get to what happened, I just want to point out that the talk actually went pretty darned well. I was utterly shocked that it was pretty much standing room only, with perhaps 50 people there to hear me. Honestly, don’t you people have anything better to do on a beautiful Saturday afternoon in August? But, seriously, the whole thing was a blast, and the assembled skeptics there didn’t even let me off the hook, as at least a couple of them asked some fairly challenging questions, one of which, I must admit, I wasn’t prepared for. In any case, my thanks go out to Dr. Jennifer Newport, skeptical Chicago pediatrician extraordinaire and organizer of my talk and the party at her apartment afterward. Between the two events she raised hundreds of dollars for the vaccination drive going on at DragonCon this weekend, Chicago Skeptics, the Women Thinking Free Foundation, and CFI-Chicago for inviting me and being such fantastic hosts.

Back to business. Science-based medicine (SBM) business, that is.

What happened while I was away could almost be characterized by the New England Journal of Medicine (NEJM) singing “Oops, I did it again.” Three weeks ago, the hallowed pages of the NEJM hosted a truly execrably credulous review article about acupuncture. So bad was the article that it “merited” the incredibly rare triple beat-down from this very blog, with posts by Steve Novella, the ever-irascible Mark Crislip, and myself in rapid succession applying the clue-by-four. As I was preparing to leave for Chicago on Thursday, I happened to look at the very latest issue of the NEJM hot off the presses, and what to my wondering (and watering–it is ragweed season) eyes should appear but an article reporting a study on the use of tai chi in treating fibromyalgia. Entitled A Randomized Trial of Tai Chi for Fibromyalgia, the study comes out of the Tufts University School of Medicine and the Newton-Wellesley Hospital in Boston and was carried out by a team led by Chenchen Wang, MD, MPH. Not surprisingly, the study has gotten a lot of play in the media, for example, in this story in the L.A. Times, which is at least reasonably restrained, probably because it an AP wire story by Marilynn Marchione, who has written some excellent articles about “alternative” medicine before. Even the usually reliable GoozNews seems smitten with this study beyond what it rates, characterizing it as “rare victory for the National Institute of Health’s National Center for Complementary and Alternative Medicine and Sen. Tom Harkin (D-IA), who routinely comes under fire for pushing funding for these types of studies.”

I’m less impressed. You’ll see what I mean in a few minutes, I hope. First, however, let’s look at the study itself.
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Posted in: Clinical Trials, Medical Academia, Science and the Media

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Does peer review need fixing?

One of the most important aspects of science is the publication of scientific results in peer-reviewed journals. This publication serves several purposes, the most important of which is to communicated experimental results to other scientists, allowing other scientists to replicate, build on, and in many cases find errors in the results. In the ideal situation, this communication results in the steady progress of science, as dubious results are discovered and sound results replicated and built upon. Of course, scientists being human and all, the actual process is far messier than that. In fact, it’s incredibly messy. Contrary to popular misconceptions about science, it doesn’t progress steadily and inevitably. Rather, it progresses in fits and starts, and most new scientific discoveries go through a varying period of uncertainty, with competing labs reporting conflicting results. To achieve consensus about a new theory can take relatively little time (for example, the less than a decade that it took for Marshall and Warren’s hypothesis that peptic ulcer disease is largely caused by H. pylori or the relatively rapid acceptance of Einstein’s Theory of Relativity) to much longer periods of time.

One of the pillars of science has traditionally been the peer review system. In this system, scientists submit their results to journals for publication in the form of manuscripts. Editors send these manuscripts out to other scientists to review them and decide if the science is sound, if the methods appropriate, and if the conclusions are justified by the data presented. This step of the process is very important, because if editors don’t choose reviewers with the appropriate expertise, then serious errors in review may occur. Also, if editors choose reviewers with biases so strong that they can’t be fair, then science that challenges such reviewers’ biases may never see print in their journals. The same thing can occur to grant applications. In the NIH, for instance, the scientists running study sections must be even more careful in choosing scientists to be on their study sections and review grant applications, not to mention picking which scientists review which grants. Biases in reviewing papers are one thing; biases in reviewing grant applications can result in the denial of funding to worthy projects in favor of projects less worthy that happen to correspond to the biases of the reviewers.

I’ve discussed peer review from time to time, although perhaps not as often as I should. My view tends to be that, to paraphrase Winston Churchill’s invocation of a famous quote about democracy, peer review is the worst way to weed out bad science and promote good science, except for all the others that have been tried. One thing’s for sure, if there’s a sine qua non of an anti-science crank, it’s that he will attack peer review relentlessly, as HIV/AIDS denialist Dean Esmay did. Indeed, in the case of Medical Hypotheses, the lack of peer review let the cranks run free to the point where even Elsevier couldn’t ignore it any more. One thing’s for sure. Peer review may have a lot of defects and blindnesses, but lack of peer review is even worse. It’s no wonder why cranks of all stripes loved Medical Hypotheses.
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Posted in: Medical Academia, Science and Medicine

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Dr. Gorski to be speaking at the Chicago Skeptics on Saturday

The week is finally here! Believe it or not, I’m heading back to my old stomping grounds in the 1990s to appear as a guest of the Chicago Skeptics.

This Saturday, August 21, I’ll be giving a talk co-sponsored by Chicago Skeptics, Women Thinking Free Foundation, and the Center For Inquiry-Chicago at the Black Rock Pub & Kitchen. My talk will be on a topic near and dear to my heart (or a topic that fills me with alarm–the two are not mutually exclusive), mainly the infiltration of pseudoscience into medicine. I’ll be sure to touch on a number of issues, and you can be sure I’ll have something to say about the recent acupuncture review that appeared in the New England Journal of Medicine and perhaps a bit about the sort of pseudoscience that’s being practiced at some of our largest and most respected cancer centers. Afterwards, you–yes, you!–can ask me about anything you want if you show up. Anything, including vaccines, skepticism, and even Bill Maher!

If you live in Chicago and want to harass me (not the way Age of Autism harasses me), head on over to the Chicago Skeptics event page and click on the link to RSVP!

ADDENDUM: Holy crap! Someone just informed me that Chicago Comic Con will be in Chicago the same weekend as me. Even worse, William Shatner will be there on Saturday, which is when I’m giving my talk. How on earth can I possibly compete with the Shat?

Posted in: Announcements, Medical Academia

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“Integrative” oncology: Trojan horse, quackademic medicine, or both?

One of the main topics that we’ve covered here on this blog over the last couple of years is the relatively rapid, seemingly relentless infiltration of pseudoscience into what should be bastions of science-based medicine (SBM), namely medical schools and academic medical centers promoted by academics who should, but apparently don’t, know better. From the very beginning, we’ve written numerous posts about this infiltration and how it has been facilitated by a variety of factors, including changes in the culture of medical academia and our own culture in general, not to mention a dedicated cadre of ideologues such as the Bravewell Collaboration, whose purpose is to blur the lines between science and pseudoscience and promote the “integration” of quackery into science-based medicine. Certainly promoters of what Dr. Robert W. Donnell termed “quackademic medicine” wouldn’t put it that way, but I would. Indeed, promoters of quackademic medicine scored a major victory last month, when a credulous piece of tripe about acupuncture passing as a review article managed to find its way into the New England Journal Medicine, a misstep that was promptly skewered by Mark Crislip, Steve Novella, and myself. It’s rare for more than two of us to write about the same topic, but it was earned by a mistake as dire as the editors of the NEJM allowing rank pseudoscience to sully its normally science-based pages.

Today, I want to riff a bit on one aspect of this phenomenon. As a cancer surgeon, I’ve dedicated myself to treating patients with cancer and then subspecialized even further, dedicating myself to the surgical treatment of breast cancer. Consequently, the interface of so-called “complementary and alternative medicine” (CAM) in the treatment of cancer both interests and appalls me. The reason for my horror at the application of CAM to cancer patients, as you might expect, is that cancer is a disease that is highly feared and can be highly deadly, depending upon the specific kind of cancer. Cancer patients deserve nothing less than the best science-based evidence that we have to offer, free of pseudoscience. Yet in even the most highly respected cancer centers, such as M.D. Anderson Cancer Center and Memorial Sloan-Kettering Cancer Center, there are departments or divisions of what is increasingly called “integrative oncology.” The claim behind “integrative oncology” is that it is “integrating the best of science-based and ‘alternative’ medicine,” but in reality all too often it is “integrating” quackery with science-based medicine. I have yet to hear an explanation of how “integrating” pseudoscience or nonscience into science-based oncology benefits cancer patients, but, then, that’s probably just the nasty old reductionist in me. Let’s find out.
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Posted in: Acupuncture, Cancer, Homeopathy, Naturopathy

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Germ theory denialism: A major strain in “alt-med” thought

The longer I’m in this whole science-based medicine thing, not to mention the whole skepticism thing, the more I realize that no form of science is immune to woo. To move away from medicine just for a moment, even though I lament just how many people do not accept evolution, for example, I can somewhat understand it. Although the basics of the science and evidence support the theory of evolution as the central organizing principle of all biology, much of the evidence is not readily apparent to those who don’t make it a calling to study biology, evolution, and speciation. It’s not like, for example, gravity, which everyone experiences and of which everyone has a “gut level” understanding. So, not unexpectedly, when the theory of evolution conflicts with a person’s religious beliefs, for most people it’s very easy to discount the massive quantities of evidence that undergird the theory of evolution. It’s not so easy to discount the evidence for gravity.

In many ways, medicine is similar to evolution, but the situation is possibly even worse. The reason is that much of the evidence in medicine is conflicting and not readily apparent to the average person. There’s more than that, though, in that there are a number of confounding factors that make it very easy to come to the wrong conclusion in medicine, particularly when looking at single cases. Placebo effects and regression to the mean, for example, can make it appear to individual patients that, for example, water (i.e., what the quackery that is homeopathy is) or placebo interventions (i.e., acupuncture) cures or improves various medical conditions. Add to that confirmation bias, the normal human cognitive quirk whereby all of us — and I do mean all of us — tend to remember information that reinforces our preexisting beliefs and to forget information that would tend to refute those beliefs — and, at the level of a single person or even practitioner, it’s very, very easy to be misled in medicine into thinking that quackery works. On the other hand, at the single patient/practitioner level, one can also see evidence of the efficacy of modern medicine; for example, when a person catches pneumonia, is treated with antibiotics, and recovers quickly. Regardless of whether they’re being used to demonstrate quackery or scientific medicine, because personal experience and the evidence that people observe at the level of the people they know can be very deceptive in medicine, science-based medicine, with its basic science underpinnings and clinical trial evidence, is necessary to try to tease out what actually works and what doesn’t.

Medicine does, however, have its version of a theory of evolution, at least in terms of how well-supported and integrated into the very fabric of medicine it is. That theory is the germ theory of disease, which, just as evolution is the organizing principle of biology, functions as the organizing principle of infectious disease in medicine. When I first became interested in skepticism and medical pseudoscience and quackery, I couldn’t envision how anyone could deny the germ theory of disease. It just didn’t compute to me, given how copious the evidence in favor of this particular theory is. It turns out that I was wrong about that, too.

On Friday there was a video released that provides a very clear, succinct explanation of germ theory denialism:

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Posted in: Chiropractic, Naturopathy, Nutrition, Vaccines

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