One of the concepts we often discuss around here is “what is disease?” As we’ve seen in the discussion of Lyme disease and so-called Morgellons syndrome, this is not always an easy question to answer. Knowing what states are disease states does not always yield a black-or-white answer. The first step is usually to define what a disease is. The next problem is to decide who in fact has that disease. The first question is hard enough, especially in disease states that we don’t understand too well. The second question can be equally tricky. To explore the scientific and philosophical issues of diagnosing an illness we will use as a model diabetes mellitus (DM). This won’t be quite as boring as you think, so don’t click away yet. (Most of the information here refers more specifically to type II diabetes, but most of it is valid for type I as well.) (more…)
Archive for Science and Medicine
EDITOR’S NOTE: Unfortunately, this weekend, I was forced to get my slides together for the upcoming SBM Conference, plus editing a manuscript for resubmission, plus working on a manuscript that I should have submitted six months ago, plus reading over some grants, plus…well, you get the idea. What this means is that, alas, I didn’t have any time to prepare one of the new, long posts that you’ve come to love (or hate). Fortunately, there are a lot of other things I’ve written out there that can be rapidly adapted to SBM. For instance, what I am about to present now. Since I wrote this, I’ve thought of a couple of things that I should have said the first time (and was kicking myself for not having done so); so publishing an updated version here allows me to rectify those omissions.
A couple of weeks ago, there was a lot of hype about a study that hadn’t been released yet. Indeed, there was a story in Wired entitled To Survive Cancer, Live With It and an editorial by the study’s lead author in Nature entitled A change in strategy in the war on cancer. Not bad for a study that hadn’t been released yet. Intrepid medical and science blogger that I am, I waited until the actual study was published a week ago the June 1 episode of Cancer Research. It’s a clever study, but the hype over it was a bit overblown. For example:
For all the weapons deployed in the war on cancer, from chemicals to radiation to nanotechnology, the underlying strategy has remained the same: Detect and destroy, with no compromise given to the killer. But Robert Gatenby wants to strike a peace.
A mathematical oncologist at the Moffitt Cancer Center, Gatenby is part of a new generation of researchers who conceive of cancer as a dynamic, evolutionary system. According to his models, trying to wipe cancer out altogether actually makes it stronger by helping drug-resistant cells flourish. Rather than fighting cancer by trying to eradicate its every last cell, he suggests doctors might fare better by intentionally keeping tumors in a long-term stalemate.
Maybe I’m being a bit picky, but what annoys me about the news reports on this study is that the concept of turning cancer into a manageable chronic disease like diabetes or hypertension is not by any means a new idea. Remember, one of my major research interests is the inhibition of tumor angiogenesis. Consequently, I know that the late, great Judah Folkman first proposed the concept of using antiangiogenic therapy to turn cancer into a chronic disease at least as early as the mid-1990’s. The only difference is the strategy that he proposed. The idea had also been floating around for quite a while before that, although I honestly do not know who first came up with it.
But let’s see what Dr. Gatenby proposes. What makes it interesting is that his study actually looks at how scientists have applied evolutionary principles to cancer until recently, argues that we’ve been doing it wrong. He then proposes a way to use the evolutionary dynamics of applied ecology. He may well be on to something. First, here’s the problem:
I’d just like to take a moment to engage in a little bit of shameless self-promotion and point out that an SBM post has actually seen print. Specifically, my post about the malign influence Oprah Winfrey’s promotion of dubious medical practices on her show (The Oprah-fication of Medicine) has been adapted (with heavy cutting and editing) into an op-ed piece in The Toronto Star, entitled Is Oprah Winfrey Giving Us Bad Medicine?
No one was more shocked than I was when the editor of Sunday Insight section of The Toronto Star contacted me earlier this week to ask if he could adapt my post to a newspaper editorial. Actually, he and his editors did the vast majority of the work in whittling my usual logorrheic prose down to a manageable size and paraphrasing the sections of the NEWSWEEK article on Oprah that I had quoted liberally from. (After all, I didn’t want to be accused of plagiarism.) It was a rather educational experience, actually. Unfortunately, reading the finished version again, I don’t think it quite makes the link between Oprah and the infiltration of pseudoscientific CAM practices into modern medicine as clear as the original post, perhaps because the context of all the other blog posts on the topic by SBM bloggers is missing, which is why I hope that some Star readers will find their way here and be able to read the full length version.
In any case, compare:
The Oprah-fication of medicine (the original, full-length blog post)
Is Oprah Winfrey Giving Us Bad Medicine? (the heavily edited op-ed piece)
And see what you think.
Some infections can be eradicated from the face of the planet. Smallpox is the one example of disease eradication to date. Smallpox still exists in US and Russian labs, but there has been no wild cases since 1977. It is, like the Dorothy, history.
Why were we able to eradicate smallpox? Three reasons:
1) There is only one form of smallpox. Unlike influenza that changes from year to year. So only one vaccine needed.
2) By what appears to be a once in a universe miracle, every county cooperated with the WHO (much like we all cooperate with the IRS) so the entire planet received the vaccine. Once enough people were vaccinated, the disease was unable to perpetuate itself and spread and so died out.
3) Unlike bacteria, there are no asymptomatic smallpox carrier states. Eradicable viruses usually cause symptomatic disease and do not result in asymptomatic, infectious carrier states that serve as a reservoir for infecting others. HIV and Herpes cause chronic asymptomatic infections and will probably never be eradicated.
There are other diseases that are theoretically eradicable, like measles and polio. They have one antigenic type, have no carrier state and, if the entire world could be vaccinated, the disease would cease to exist in the wild. I am sure there would be biologic weapons labs that would always carry a vial or 2 of every infection. Just to be safe.
In the US children must have proof of vaccination before entering the public school system, although it is becoming easier in many states for parents to gain exemptions from this requirement. In the UK there is no such requirement. This distinction has allowed for a comparison of the impact of scaremongering about the safety of vaccines and the effectiveness of campaigns to improve vaccination rates.
In the UK the scare that the MMR vaccine may be connected to autism (it isn’t) triggered by the bogus study by Andrew Wakefield resulted in a precipitous drop in vaccination rates down to about 78% overall. This is far below what is necessary for herd immunity, when immunity is prevalent enough to prevent a disease from spreading around a population. And the 78% figure is an average – but there are pockets where the number is even lower. This resulted in a surge of measles – from a low of less than 100 cases per year to 1,348 cases in 2008. The surge contniues despite an aggressive campaign to inform the public about the safety of the MMR vaccine.
By contrast the US has seen continued high overall vaccination rates of about 90%. The MMR and other vaccine scare came to the US a bit later than the UK but it is in full swing here, without much effect on overall vaccination rates. However, we are beginning to see the emergence of low vaccination rates in specific communities, with subsequent outbreaks of measles (131 cases in 2008), mumps, and whooping cough.
Unfortunately, a frequent topic on SBM has been the anti-vaccine movement, personified these days by celebrity spokesmodel for Generation Rescue Jenny McCarthy and her dimmer than dim boyfriend comedian and actor Jim Carrey. Unfortunately, it is a topic that is unlikely to go away. We’ve all speculated why the anti-scientific emotion-based notion that vaccines somehow must cause autism persists in spite of mountains of evidence to the contrary, but I think the question goes much deeper than that because it’s not just about vaccines. The anti-vaccine movement is but one of the most visible components of a much deeper problem in our public discourse, a problem that values feelings and personal experience over evidence, compelling stories and anecdotes over science.
I’m referring to the Oprah-fication of medicine in America.
In the three prior posts of this series I tried to analyze some of the defects in the randomized clinical rials (RCTs) of homeopathic remedies for childhood diarrhea. The first entry showed that the first two RCTs’ (done in Nicaragua) methods could not produce a meaningful result because of the way the RCTs were set up (methods.) The second entry showed that the results obtained in the first two trials were meaningless clinically even if assumed to have resulted from more legitimate methods. The same applied to the third trial in Nepal, analyzed in the third entry.
This entry will suggest that the authors’ fourth paper (Jacobs J, Jonas WB, Jimenez-Perez M, Crothers D. Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials. Pediat Inf Dis J, 2005;22:229-234.)- a meta-analysis (MA) of the data from the three RCTs resulted in conclusions equally as meaningless as those of the three trials.
The MA authors – several of the same workers from the three RCTs – begin by agreeing that the data from the RCTs, taken individually, were of borderline significance:
In our previous three studies, we evaluated the use of individualized homeopathic treatment of childhood diarrhea … The results of the two larger studies (n = 81, n = 116) were just at or near level of statistical significance. Because all three studies followed the same basic study design , […] we analyzed the combined data from these three studies to obtain greater statistical power. In addition we conducted a meta-analysis of effect-size difference […] to look for consistency of effects.
MAs and systematic reviews (SRs) are the two consensus methods for summarizing data from multiple individual studies. The inclusion and search methods of RCTs for SRs and MAs are similar, but the objectives of the two are a bit different, as are the forms of the reports. In SRs, the results are summarized in more in narrative form, whereas in MAs the data are treated mathematically and the results are defined in statistical terms. Thus authors of SRs are freer to speculate on the degree of confidence that a method is effective based on what is shown by the numbers of positive and negative RCTs collected. Authors of MAs usually limit their comments to what the mathematical formulation of the summarized data show.
An audience member at a recent NYC Skeptics meeting asked me how I handled conflict surrounding strongly held beliefs that are not supported by conclusive evidence. As a dentist, he argued, he often witnessed professionals touting procedure A over procedure B as the “best way” to do X, when in reality there are no controlled clinical trials comparing A and B. “How am I to know what’s right in these circumstances?” He asked.
And this is more-or-less what I said:
The truth is, you probably can’t know which procedure is better. At least, not at this point in history. The beauty of science is that it’s evolving. We are constantly learning more about our bodies and our environment, so that we are getting an ever-clearer degree of resolution on what we see and experience.
It’s like having a blurry camera lens at a farm. At first we can only perceive that there are living things moving around on the other side of the lens – but as we begin to focus the camera, we begin to make out that the animals are in the horse or cattle family. With further focus we might be able to differentiate a horse from a cow… and eventually we’ll be able to tell if the horse has a saddle on it, and maybe one day we’ll be able to see what brand of saddle it is. Each scientific conundrum that we approach is often quite blurry at the onset. People get very invested in their theories of the presence or absence of cows, and whether or not the moving objects could in fact be horses. Others say that those looking through the camera contradict one another too much to be trusted – that they must be offering false ideas or willfully misleading people about the picture they’re describing.
In fact, we just have different degrees of clarity on issues at any given point in time. This is not cause for alarm, nor is it a reason to abandon our cameras. No, it just gives us more reason to continue to review, analyze, and revise our understanding of the picture at hand. We should try not to make more out of photo than we can at a given resolution – and understand that contradicting opinions are more likely to be evidence of insufficient information than a fundamental flaw of the scientific method.
Last week I discussed a clinical trial comparing standardized acupuncture, individualized acupuncture, placebo-acupuncture, and usual care. In that discussion I emphasized the comparison between the three acupuncture groups, which did not show any difference in outcome. These results are consistent with the overall acupuncture literature, which shows in the better controlled trials that it does not matter where you stick the needles or even if you stick them through the skin. Therefore the scientific evidence fails to reject the null hypothesis (that acupuncture does not work). This did not stop the press from declaring, almost uniformly, that acupuncture works for back pain, contributing to the public misunderstanding of clinical science.
This week I am going to focus on the other aspect of the trial – the one the researchers and the press chose to focus on – the comparison of the two real and one placebo acupuncture arms to “usual care.” This too was misrepresented by the press, encouraged by the overinterpretation of the evidence by the researchers.
In the comments to Part I of this discussion David Gorski correctly pointed out that the study in fact did not even constitute a comparison of acupuncture to standard medical treatment. He is absolutely correct, and the many reasons for this are worth explaining in detail. Understanding the technology of clinical trials is central to science-based medicine, including all of their pitfalls and limitations. For practical and logistical reasons there is almost never a perfect clinical trial, but mischief only ensues when limitations are not understood, leading to a misinterpretation (and almost always an overinterpretation in the direction of the researcher’s bias) of the evidence.
I recently saw a 14 year old girl in my office with a 2 day history of severe abdominal cramps, bloody diarrhea, and fever. Her mother had similar symptoms as did several other members of her household and some family friends. After considerable discomfort, everyone recovered within a few days. The child’s stool culture grew a bacterium called Campylobacter.
Campylobacter is a nasty little pathogen which causes illness like that seen in my patient, but can also cause more severe disease. It is found commonly in both wild and domestic animals. But where did all these friends and family members get their campylobacter infections? Why, from their friendly farmer, of course!
My patient’s family and friends had taken a weekend pilgrimage to a family-run farm in Buck’s County, Pennsylvania. They saw farm animals and a working farm. And they all drank raw milk. Why raw milk? Because, as they were told and led to believe, raw milk is better. Better tasting and better for you.
In 1862, the french chemist Louis Pasteur discovered that heating wine to just below its boiling point could prevent spoilage. Now this process (known as pasteurization) is used to reduce the number of dangerous infectious organisms in many products, prolonging shelf life and preventing serious illness and death. But a growing trend toward more natural foods and eating habits has led to an interest in unpasteurized foods such as milk and cheese. In addition to superior taste, many claim that raw milk products provide health benefits not found in the adulterated versions. Claims made about the “good bacteria” (like Lactobacillus) conquering the “bad” bacteria (like Campylobacter, Salmonella, and E. coli) in raw milk are pure fantasy. Some even claim that the drinking of mass-produced, pasteurized milk has resulted in an increase in allergies, heart disease, cancer, and a variety of other diseases. Again, this lacks any scientific crediblity.