I intended to read Sam Kean’s new book The Violinist’s Thumb: And Other Lost Tales of Love, War, and Genius as Written by our Genetic Code just for fun. I was expecting a miscellany of trivia loosely gathered around the theme of DNA. But I found something much more worthwhile that I thought merited a book review to bring it to the attention of our readers. Kean interweaves entertaining stories into a somewhat disjointed but nonetheless valuable history and primer of genetics. The title refers to Paganini, whose DNA created the unusual joint flexibility that facilitated his unprecedented feats of virtuosity on the violin.
Archive for Basic Science
Over the years, I’ve written a lot about “personalized medicine, mainly in the context of how the breakthroughs in genomic medicine and data pouring in from the Cancer Genome Atlas is providing the raw information necessary for developing truly personalized cancer therapy. The problem, of course, is analyzing it and figuring out how to apply it. Another problem, of course, is developing the necessary targeted drugs to attack the pathways that are identified as being dysregulated in cancer cells. Oh, and there’s that pesky evolution of resistance to antitumor therapies. Indeed, most recently, the Cancer Genome Atlas is bearing fruit in breast cancer (a study that I’ve been meaning to blog about).
One problem with modeling the pathways based on next generation sequencing data and expression profiling is testing whether therapies predicted to work from these analyses actually do work without actually testing potentially toxic drugs on patients. Cell culture is notoriously unreliable as a predictor. However, there is another way that’s intriguing. Unfortunately, as intriguing as it is, it has numerous problems, and, unfortunately, it’s being prematurely marketed to patients. Although I had heard of this technique as a research tool before, I learned about its marketing to patients when I came across an article by Andrew Pollack in the New York Times entitled Seeking Cures, Patients Enlist Mice Stand-Ins. Basically, it’s about a trend in science and among patients to use custom, “personalized’ mouse xenograft models in order to do “personalized” therapy:
As part of my ongoing effort to make sure that I never run out of blogging material, I subscribe to a number of quack e-mail newsletters. In fact, sometimes I think I’ve probably overdone it. Every day, I get several notices and pleas from various wretched hives of scum and quackery, such as NaturalNews.com, Mercola.com, and various antivaccine websites. I think of it as my way of keeping my finger on the pulse of the antiscience and pseudoscience wing of medicine, but I must admit that I don’t really read them all, but they do allow me to know what the quacks are selling and what new arguments they’re coming up with without actually going to each of their websites. I can then judge by the headlines and the blurbs included in the e-mails whether I think it’s worth it to go to the website itself and, of course, whether the topic might represent fodder for a good blog post. I will admit that not all the sites I monitor are as loony as the Health Ranger’s. In fact, I monitor the blogs and websites of the National Center for Complementary and Alternative Medicine (NCCAM), various naturopath organizations, and the like in order to learn of the “respectable” arguments being used to tout various nostrums.
Sometimes—albeit rarely—I even learn about some interesting new science.
One of the most common themes (besides antivaccine hysteria, claims that diet can prevent 95% of all cancers, etc.) tends to be one of a variety of pitches for various “cures” of serious diseases like cancer and heart disease that “they” don’t want you to know about; i.e., the Kevin Trudeau gambit. Who this “they” is can range from doctors to pharmaceutical companies to universities to the government, but the central message is that someone out there doesn’t want you to know The Truth. A variation of this sort of appeal is the claim that there is a promising new therapy, a cure even, usually natural, that is languishing somewhere because it can’t be patented, because pharmaceutical companies would lose money if it were ever validated and brought into clinical use, or because it goes against current medical dogma. It doesn’t even have to be natural. After all, dichloroacetate (DCA) is not exactly “natural.” After it was shown to have promise in animal models, a pesticide salesman named Jim Tassano sold DCA bought from chemical companies to desperate cancer patients from a website that claimed to be selling it only for pets with cancer, a ruse that fooled no one. Yet the “natural treatment” crowd embraced it whole-heartedly because it looked as though sellers of DCA were sticking it to The Man.
I do not want to get all angsty and omphaloskeptic, but I have been thinking more of late about the purpose of the blog and my role in it. Blogs,and the people who write them, are ephemeral. It takes a unique personality and commitment to churn out these essays and commit them to the ether. Especially since Michelson and Morley.
I have never given much thought as to who our readers are, at least as a composite. I read most of the comments on every entry and have certainly developed a mental picture of some of our regular commenters, although I suspect I probably do not have even the gender correct most of the time. The commenters represent a tiny fraction of the regular readers and an even smaller fraction of occasional readers. It occurs to me I haven’t a clue who the real audience of this blog is.
I write first for my own education and entertainment, then for the slightly bored and overwhelmed medicine resident, since that is who I spend most of my time educating at work. Someone educated with an understanding of basic medicine but has more important things on their mind than a need for a detailed understanding of why homeopathy is complete nonsense. I doubt the majority of my readers are health care workers and I suspect continuing medical education is not a major part of the blog.
I never considered SBM to be a consumer protection group, but this week my wife showed me a half page advertisement in the local paper, and I realized that not only was the advertisement a good topic for blogging, but consumer protection is a fundamental result of this blog. There really is no site on the interweb that looks at both SCAM and real medicine with quite the same skeptical eye. Here is the headline:
A Special Wellness Report
New Medicine Based On An 88- Year Old Theory By Albert Einstein Can Help Almost Everyone Who Is Sick Or Injured! (more…)
It feels like I live in the real world example of Ray Bradbury’s All the Summer in a Day but for the last two weeks we have had sun and heat and it has been glorious. I get Christmas and Thanksgiving and New Years as vacation, but who needs that? I need July and August to live the vida loca in the Oregon summer. Who wants to blog when I can be outside, at concerts, golfing, hiking and…
Yes Dr. Gorski. I did agree to write an entry every other Friday. Yes Dr. Gorski. I know you have the documentation. Yes Dr. Gorski, I do not want any of that information made public. No one needs to know that I wanted to be a naturopath when I was young. Sigh. Yes, Sir, I will get to blogging. Damn those youthful indiscretions. Let’s see how little I can do and meet my obligations with the powers that be.
My professional career is based upon inflicting death, and in my time I have obliterated uncountable numbers of unicellular organisms. If there were such a thing as Karma, I would certainly return in the next life as a rabbit in a syphilis lab. But there isn’t, and I can kill and kill with a clean soul. There is no guilt or hesitation in killing unicellular life, or even multi-cellular life, as long as it cannot be seen without a microscope. I start to get a wee bit squeamish as soon as I can see a life form. I tend to not kill bugs or animals, unless, of course, they can be eaten. If it tastes good, all bets are off. But as a tree hugger, I tend to look upon killing wildlife and extinctions as a bad thing. (more…)
From the very outset, the founders of Science Based Medicine have have emphasized the importance of plausibility in the critical evaluation of scientific claims in medicine. What exactly does “plausibility” mean, and how should we apply it in science? My simple definition of plausibility would be “the likelihood that a premise is true.” The application in science is a little more complicated.
Consciously or unconsciously, we all consider plausibility in interpreting events in our lives. For example, if one of your coworkers showed up late for work and grumbled about a traffic jam, you would likely accept his story without question. If, instead, the same coworker attributed his tardiness to an alien abduction, you would not be so charitable. In each case, he has provided the same level of evidence: his anecdotal account. You are likely to accept one story and reject the other because of a perceived difference in the plausibility. The skeptic’s mantra “Extraordinary Claims Require Extraordinary Evidence” expresses this concept in a qualitative way.
Evidence-based medicine has traditionally ignored plausibility when interpreting the evidence for a medical intervention. Science-based medicine, as envisioned by the creators of this blog, includes plausibility when making these judgements.
Since experiment research employs rigorous controls, and statistical criteria, you might assume that plausibility is not an issue, however, this is not entirely true. An article written by John Ioannidis entitled “Why Most Published Research Findings Are False” is cited frequently as a reference for the impact of plausibility on the interpretation of research results. This article enumerates numerous factor leading to erroneous research conclusions. Most of them have been dealt with on this blog at one time or another. To me, the most eye-opening aspect of the paper was a quantitive approach to the influence of plausibility in interpreting positive research findings. I was never taught this approach in medical school, or in any other venue. When it comes to implausible hypotheses, the traditional P-value can be very misleading.
As good as Ioannidis’ article is, it is not easy reading for the statistically or mathematically challenged. What I attempt to do in this post is to demonstrate the importance of plausibility in graphic format, without a lot of complex math. If you can grasp the concepts in this post, you will have an understanding that many researchers, and consumers of research, lack.
Voodoo science is a sort of background noise, annoying but rarely rising to a level that seriously interferes with genuine scientific discourse… The more serious threat is to the public, which is not often in a position to judge which claims are real and which are voodoo. Those who are fortunate enough to have chosen science as a career have an obligation to inform the public about voodoo science.
– Robert L. Park, PhD, 20001
Imagine you are an ordinary person with limited knowledge of science and medicine, and you see this 2010 video on tai chi and qi gong by the National Center for Complementary and Alternative Medicine (NCCAM) — one of the agencies that make up the National Institutes of Health (NIH). I am certain that the solemn voice of the Director of NCCAM, Dr. Josephine Briggs, talking about “rigorous scientific research” and “accurate, authoritative information on complementary and alternative medicine,” will leave you with a strong sense of confidence in her message.
In addition, despite the fine-print and the disclaimer, the appearance of Dr. Briggs in the video could be broadly viewed as a sign of tacit endorsement. Often, the very fact that a treatment is associated with the government is already a de facto stamp of approval and a warranty of efficacy. For instance, the publication below by the California Department of Consumer Affairs states that the NIH formally “endorses” acupuncture, simply because in 1997, a panel of scientists assessed its use and effectiveness for a variety of conditions. Since 1997 the scientific review of acupuncture by NIH has become synonymous with its endorsement, despite the fact that as a federal research agency, the NIH does not endorse any product, service, or treatment.
In October 26, 2011, a few weeks after Steve Jobs’ death, Josephine Briggs decided to do something she has never done before: she put an explicit disclaimer on her blog:
When making treatment decisions, unproven “alternative medicine” approaches should not replace conventional medical care approaches known to be useful or helpful. Simply put, the evidence is not there (emphasis added).2
Three paragraphs down the page, she goes on — with a candor rarely seen from her — that given the recent news about Steve Jobs’ choices for cancer treatment, all health decisions “should be guided by the best available evidence.”
Acupuncture has been a frequent topic on this blog because, of all the “complementary and alternative medicine” (CAM) modalities out there, it’s arguably the one that most people accept as potentially having some validity. The rationale behind acupuncture is, as we have explained many times before, little different than the rationale behind any “energy healing” method (like reiki, for example) in that it claims to redirect the flow of “life energy” (the ever-invoked qi). The only difference is that acupuncturists claim to bring this therapeutic qi rearrangement about by sticking thin needles into the pathways in the body through which this qi is fantasized to flow. These pathways, called meridians, are just as much a fantasy as qi itself or the “universal source” that reiki masters claim to be able to channel through themselves and into believers. Contributing to the popularity of acupuncture is its mythology as having been routinely practiced for over two thousand years, a myth that was the creation of Chairman Mao, who elevated what was a marginal practice at the time to a modality that the state supported and promoted (1,2,3,4).
In addition, because acupuncture involves sticking actual metal objects into the skin rather than simply laying on hands or making magical gestures over the patient, it retains some credibility, even among doctors. It doesn’t matter that, reviewing the totality of the research, one finds that it doesn’t matter where you stick the needles or even if you stick the needles in the skin. The results are the same and indistinguishable from placebo. The inescapable conclusion is that acupuncture is placebo medicine with needles. Personally, I’d prefer my placebo medicine without needles, but that’s just me.
Yet, the studies keep rolling in, trying desperately to demonstrate that acupuncture works or assuming that acupuncture works . Two more popped up within the last couple of weeks, and one of them, if you read the press releases, sounds really convincing. As is frequently the case, for this latter study, there is less to it than meets the eye. I’ll start, however, with a study that is a followup to a study I blogged about a couple of years ago that I characterized as another overhyped acupuncture study misinterpreted. This one, thankfully, is not nearly as hyped as the study from two years ago—or as the second study I will discussed, but it is very instructive how the original misinterpreted story is leading to a classic CAM “bait and switch” applied to acupuncture.
Consider this scenario: You’re in good health and take no prescription drugs. You use the following remedies occasionally:
- Excedrin for the rare migraine
- Arnica 30CH for bumps and bruises
- Echinacea capsules, when you feel a cold coming on
Today you look in your cupboard, and notice all three products expired last year. Would you still consider taking any of them? Why or why not?
Your answer is probably influenced by a number of factors, including perceptions of risk and benefit. I’ve encountered patients who believe that drugs are less active as they near the expiration date, and others who see expiry dates solely as marketing ploy from Big Pharma. Few understand how they’re calculated.
Over the past few months I’ve written several posts on different aspects of drug development and testing, including drug interactions, fillers and excipients in drug products, the equivalence testing of generic drugs, and the management of drug allergies. I’ve done this for two reasons. The first is to develop a SBM-oriented resource for common questions and misconceptions about the mechanics of modern medicines. The second, less obvious reason for these posts has been to illustrate the serious credibility gaps with CAM therapies. Largely because of a lax regulatory framework, the CAM industry has ballooned into a multi-billion dollar market without answering basic questions that should be asked of any supplement or drug, “alternative” or otherwise. What’s not well known to consumers, but is glaringly obvious to SBM advocates, is that CAM largely ignores issues of pharmacology: understanding how a chemical substance, once consumed, behaves in the body. It’s critical to scientific medicine, but an unnecessary step for CAM, where there’s no need to determine if a product has a beneficial biological effect before selling it. Fundamental tests in medicine, like the identification and isolation of an active ingredient, or understanding dose-effect relationships, are simply ignored. As David Gorski and Mark Crislip have pointed out over the past week, we have a reality bias at SBM. And this bias is equally jarring when it comes to considering expiry dates for products: real drugs, and also CAM.
On Friday, you might have noticed that Mark Crislip hinted at a foreshadowing of a blog post to come. This is that blog post. He knew it was coming because when I saw the article that inspired it, I sent an e-mail to my fellow bloggers marking out my territory like a dog peeing on every tree or protecting my newfound topic like a mother bear protecting her cubs. In other words, I was telling them all to back off. This article is mine.
Mine! Mine! Mine! I tell you!
My extreme territorial tendencies (even towards my friends and colleagues) notwithstanding on this issue aside, if you read Mark’s post (and if you didn’t go back and read it now—seriously, go now), you might also remember that he was discussing a “reality bias” in science-based medicine (SBM), a bias that we like to call prior plausibility. In brief, positive randomized clinical trials (RCTs) testing highly implausible treatments are far more likely to be false positives than RCTs testing more plausible treatments. That is the lesson that John Ioannidis has taught us and that I’ve written about multiple times before, as have other SBM bloggers, most prominently Kimball Atwood, although nearly all of us have chimed in at one time or another about this issue.
Apparently a homeopath disagrees and expressed his disagreement in an article published last week online in Medicine, Health Care, and Philosophy entitled Plausibility and evidence: the case of homeopathy. You’ll get an idea of what it is that affected us at SBM like the proverbial matador waving his cape in front of a bull by reading this brief passage from the abstract:
Prior disbelief in homeopathy is rooted in the perceived implausibility of any conceivable mechanism of action. Using the ‘crossword analogy’, we demonstrate that plausibility bias impedes assessment of the clinical evidence. Sweeping statements about the scientific impossibility of homeopathy are themselves unscientific: scientific statements must be precise and testable.
Scientific. You keep using that word. I do not think it means what you think it means. Of course, his being a homeopath is about as close to a guarantee as I can think of that a person doesn’t have the first clue what is and is not scientific. If he did, he wouldn’t be a homeopath. Still, this particular line of attack is often effective, whether yielded by a homeopath or other CAM apologist. After all, why not test these therapies in human beings and see if they work? What’s wrong with that? Isn’t it “close-minded” to claim that scientific considerations of prior plausibility consign homeopathy to the eternal dustbin of pseudoscience?
Not at all. There’s a difference between being open-minded and being so “open-minded” that your brains threaten to fall out. Guess which category homeopaths like Rutten fall into. But to hear them tell it, homeopathy is rejected because because we scientists have a “negative plausibility bias” towards it. At least, that’s what Rutten and some other homeopaths have been trying to convince us. This article seems to be an attempt to put some meat on the bones of their initial trial balloon of this argument published last summer, which Steve Novella duly deconstructed.
Before I dig in, however, I think it’s necessary for me to “confess” my bias and why I think it should be your bias too.