A number of buzz-words appear repeatedly in health claims, such as natural, antioxidants, organic, and inflammation. Inflammation has been implicated in a number of chronic diseases, including diabetes, Parkinson’s, rheumatoid arthritis, allergies, atherosclerosis, and even cancer. Inflammation has been demonized, and is usually thought of as a bad thing. But it is not all bad.
In a study in Nature Medicine in September 2011, a research group led by Dr. Umut Ozcan at Children’s Hospital Boston (a teaching hospital affiliated with Harvard Medical School) reported that two proteins activated by inflammation are crucial to maintaining normal blood sugar levels in obese and diabetic mice. This could be the beginning of a new paradigm. Ozcan says:
This finding is completely contrary to the general dogma in the diabetes field that low-grade inflammation in obesity causes insulin resistance and type 2 diabetes. For 20 years, this inflammation has been seen as detrimental, whereas it is actually beneficial.
Increasing levels of these inflammatory signals might actually be therapeutic in diabetes and obesity. On the other hand, they might worsen inflammatory diseases like asthma and rheumatoid arthritis. Ozcan’s findings are intriguing and might eventually lead to new treatments, but there are no clinical applications as yet.
Over the last couple of weeks, I’ve been spending a lot of time (and, characteristically, verbiage) analyzing the phenomenon known as Dr. Stanislaw Burzynski and his “cancer cure” known as antineoplastons. In part I of this series, Stanislaw Burzynski: Bad medicine, a bad movie, and bad P.R., I used the legal threats against bloggers criticizing the credulous promotion by the British press of fundraising campaigns to send children with terminal cancer to the Burzynski Clinic and the promotion of the medical propaganda movie Burzynski The Movie: Cancer Is Serious Business to review the movie’s claims and look into Burzynski’s claims for antineoplastons. Not surprisingly, I found the evidence for extravagant claims for their anticancer effects unconvincing. In part II, Dr. Stanislaw Burzynski’s “personalized gene-targeted cancer therapy”: Can he do what he claims for cancer?, I looked into Dr. Burzynski’s recent efforts to “diversify his portfolio, in which he has apparently decided to ride the new wave of genomic medicine to claim he can do “personalized, gene-targeted cancer therapy.” I concluded that he does appear to do that, only very badly, in essence “making it up as he goes along.”
In this third and final part, I want to come back to antineoplastons, because it has been pointed out to me that there is an aspect of this story that has received little attention. One reader in particular has helped enormously in my education about this aspect of the Burzynski saga. I wish I could credit this person by name, but, for reasons I fully understand, I can’t. However, this person’s input was essential, and I’ve even appropriated (with permission, of course) a little bit of text here and there from our e-mail exchanges to “integrate” into this post. Putting this together with information in my previous posts, I think we can come to some conclusions about what it is that Dr. Burzynski is really doing.
Burzynski and an orphan drug
In the first part of this series, I pointed out that back in the 1970s Dr. Burzynski claimed to have discovered cancer-fighting substances in human urine, which he dubbed “antineoplastons,” claiming that patients with cancer had lower levels of these substances in their blood and urine. However, I was pretty vague about just what these substances were, other than to point out that they were modified amino acids and that since 1980 Dr. Burzynski has been synthesizing them in a chemistry lab rather than isolating them from urine as he had done up until then. This vagueness came simply from my interest in moving straight to looking at Burzynski’s claims rather than what these substances were. In retrospect, that might have been a mistake. The reason is that understanding what two of Burzynski’s antineoplastons are is critical to understanding what he is doing with them and why he might occasionally appear to be observing an antitumor response.
Last week, I wrote a magnum opus of a movie review of a movie about a physician and “researcher” named Stanislaw Burzynski, MD, PhD, founder of the Burzynski Clinic and Burzynski Research Institute in Houston. I refer you to my original post for details, but in brief Dr. Burzynski claimed in the 1970s to have made a major breakthrough in cancer therapy through his discovery of anticancer substances in the urine that he dubbed “antineoplastons,” which turned out to be mainly modified amino acids and peptides. Since the late 1970s, when he founded his clinic, Dr. Burzynski has been using antineoplastons to treat cancer. Over the last 25 years or so, he has opened a large number of phase I and phase II clinical trials with little or nothing to show for it in terms of convincing evidence of efficacy. Worse, as has been noted in a number of places, high doses of antineoplastons as sodium salts are required, doses so high that severe hypernatremia is a concern.
Although antineoplastons are the dubious cancer therapy upon which Dr. Burzynski built his fame, they aren’t the only thing he does. Despite the promotion of the Burzynski Clinic as using “nontoxic” therapies that “aren’t chemotherapy” by “natural medicine” cranks such as Joe Mercola and Mike Adams, Dr. Burzynski’s dirty little secrets, at least as far as the “alternative medicine” crowd goes, are that (1) despite all of the attempts of Dr. Burzynski and supporters to portray them otherwise antineoplastons are chemotherapy and (2) Dr. Burzynski uses a lot of conventional chemotherapy. In fact, from my perspective, it appears to me as though over the last few years Dr. Burzynski has pivoted. No longer are antineoplastons the center of attention at his clinic. Rather, these days, he appears to be selling something that he calls “personalized gene-targeted cancer therapy.” In fact, it’s right there in the first bullet point on his clinic’s webpage, underlined, even! Antineoplastons aren’t even listed until the third bullet point.
But what is “personalized gene-targeted cancer therapy,” according to Dr. Burzynski? Here is how it is described:
And the Lord spake, saying, “First shalt thou take out the Holy Pin. Then shalt thou count to three, no more, no less. Three shall be the number thou shalt count, and the number of the counting shall be three. Four shalt thou not count, neither count thou two, excepting that thou then proceed to three. Five is right out. Once the number three, being the third number, be reached, then lobbest thou thy Holy Hand Grenade of Antioch towards thy foe, who, being naughty in my sight, shall snuff it.
Cleric from Monty Python and the Holy Grail
I’ve always wondered about the power of the number three. When it comes to quackery propaganda movies, certainly three seems to be the magic number. For example, The Greater Good, an anti-vaccine propaganda film, features three anecdotes, three children allegedly suffering from vaccine injury, and it interspersed its interviews with experts, both real (such as Dr. Paul Offit) and phony (such as Barbara Loe Fisher) with vignettes from these children’s stories interspersed between them in a highly biased manner. I have to wonder whether these cliches are taught in film school, given that they seem to be so common. Such were the thoughts running through my brain as I watched the latest medical propaganda film by writer/producer Eric Merola that’s floating around the blogosphere and the film circuit, Burzynski The Movie: Cancer Is Serious Business. In this movie, there are three testimonials, and, if anything, they are far more manipulative than even the testimonials featured in The Greater Good, because each of them are of the type that portrays doctors as sending a patient home to die; that is, until a “brave maverick doctor,” one Stanislaw R. Burzynski, MD, PhD, comes to the rescue with his unconventional and unproven therapy. The only difference is that this film counts testimonials up to the number three in the beginning as “proof” that Burzynski can cure cancer before lobbing the Holy Hand Grenade of Burzynski towards its foes in the hopes that, being naughty in the filmmaker’s sight, the FDA and Texas Medical Board will snuff it. Or, as a caption says right at very the beginning of the movie:
This is the story of a medical doctor and PhD biochemist who has discovered the genetic mechanism that can cure most human cancers. The opening 30 minutes of this film is designed to thoroughly establish this fact — so the viewer can fully appreciate the events that follow it.
It turns out that the grenade is a dud.
Every so often, I come across studies that leave me scratching my head. Sometimes, these studies are legitimate scientific studies that have huge flaws or come from an assumption that is very off-base. Other times, they involve what Harriet Hall has termed “tooth fairy science,” wherein the tools of science are used to study a phenomenon that is fantastical, whose very existence hasn’t been demonstrated. Many such studies, not surprisingly, are studies of “complementary and alternative medicine” (CAM) or “integrative medicine” (IM). Modalities like reiki (which is faith healing that substitutes Eastern mysticism for Christian beliefs) and homeopathy (which is, when you boil it down to its essence, sympathetic magic) fall into the category of therapeutic modalities that are based on fantasy but are studied as with the latest tools of science, producing no end to confusing noise. This “tooth fairy science” has, over the last few years, reached its epitome in the application of the latest genomics technology to, in essence, magic, and I’ve recently come across an incredible example of just such a thing. But, first, let’s take a step back to what is going on in medical science now before I introduce a concept that I’ve dubbed “woo-omics.”
A prelude to woo-omics: Genomics, proteomics, everywhere an “omics”
One of the most difficult problems in science-based medicine is how to do a better job identifying which patients will respond to which treatments. Clinical trials, by their very design, have to look at average responses in populations. In essence, a treatment is compared to either placebo or standard-of-care, a choice mainly driven by ethics and whether effective treatments exist for the condition being studied. It is then determined using statistics whether a significant difference exists between the two groups. The difficulty, as any clinician knows, is applying the results of clinical trials to individual patients. In any population, there is, after all, a range of responses to any drug or treatment, and it would be desirable to be able to predict which patients will fall at the end of the bell-shaped curve where the treatment is most effective and which will fall at the end of the curve where the treatment works poorly or not at all.
I have mixed emotions regarding Breast Cancer Awareness Month. On the one hand, I look forward to it because it provides us with a pretext to get out science-based messages about breast cancer and to highlight a lot of the cool science that we do at our cancer center. On the other hand, the quacks see an opportunity in Breast Cancer Awareness Month to spread their message too. That message, not surprisingly, generally involves attacking science-based modalities for the detection and treatment of breast cancer and promoting their “alternative” methods. For example, last year, Christiane Northrup promoted thermography as somehow being better than mammography for the early detection of breast cancer. It’s not. Yet there she is this year again, still promoting the same nonsense. In years past, I’ve seen people like Dennis Byrne promoting a link between abortion and breast cancer, a link that is not supported by science. I’ve seen the likes of Mike Adams claiming that Breast Cancer Awareness Month is nothing more than a conspiracy by the male-dominated “cancer industry” to keep women down and misinformation about “myths” of breast cancer while likening the “cancer industry” to Nazi extermination camp commanders and chemotherapy to Zyklon-B. I kid you not about that last part. Indeed, during October, I frequently get to look forward to images like this one (click for a larger image):
Or this one:
“Strong Medicine”: Ted Kaptchuk and the Powerful Placebo
At the beginning of the first edition of The Web that has no Weaver, published in 1983, author Ted Kaptchuk portended his eventual academic interest in the placebo:
A story is told in China about a peasant who had worked as a maintenance man in a newly established Western missionary hospital. When he retired to his remote home village, he took with him some hypodermic needles and lots of antibiotics. He put up a shingle, and whenever someone came to him with a fever, he injected the patient with the wonder drugs. A remarkable percentage of these people got well, despite the fact that this practitioner of Western medicine knew next to nothing about what he was doing. In the West today, much of what passes for Chinese medicine is not very different from the so-called Western medicine practiced by this Chinese peasant. Out of a complex medical system, only the bare essentials of acupuncture technique have reached the West. Patients often get well from such treatment because acupuncture, like Western antibiotics, is strong medicine.
Other than to wonder if Kaptchuk had watched too many cowboy ‘n’ Native American movies as a kid, when I first read that passage I barely blinked. Although the Chinese peasant may have occasionally treated someone infected with a bacterium susceptible to his antibiotic, most people will get well no matter what you do, because most illnesses are self-limited. Most people feel better even sooner if they think that someone with special expertise is taking care of them. If you want to call those phenomena the “placebo effect,” in the colloquial sense of the term, fine. That, I supposed, was what Kaptchuk meant by “strong medicine.”
Turns out I was mistaken. Let’s briefly follow Kaptchuk’s career path after 1983. In the 2000 edition of The Web, he wrote:
There has been an ongoing debate about placebos on SBM, both in the articles and in the comments. What does it mean that a treatment has been shown to be “no better than placebo?” If our goal is for patients to feel better and they feel better with placebos, why not prescribe them? Do placebos actually do anything useful? What can science tell us about why a patient might report diminished pain after taking an inert sugar pill? The subject is complex and prone to misconceptions. A recent podcast interview offers a breakthrough in understanding.
On her Brain Science Podcast Dr. Ginger Campbell interviewed Dr. Fabrizio Benedetti, a physician and clinical neurophysiologist who is one of the world’s leading researchers on the neurobiology of placebos. A transcript of the interview [PDF] is available on her website for those who prefer reading to listening. The information Dr. Benedetti presents and the expanded remarks by Dr. Campbell after the interview go a long way towards explaining the placebo phenomenon and its consequences for clinical medicine. Dr. Campbell also includes a handy list of references. I’ll try to provide a summary of the main points, but I recommend reading or listening to the original.
A common misconception is that the response to placebos is a purely subjective psychological response involving only the cortical level of the brain; but evidence is accumulating that real, measurable, objective subcortical neurophysiologic phenomena are involved. One of the first hints was a 1978 study showing that the placebo response to pain could be blocked by naloxone, a narcotic antagonist drug, indicating that the placebo must have actually caused an increase in endogenous opioids. (more…)
As most readers of the blog know, I am mostly an Infectious Disease doc. I spend my day diagnosing and treating infections and infectious complications. It is, as I have said before, a simple job. Me find bug, me kill bug, me go home. Kill bug. It is the key part of what I do everyday, and if there is karmic payback for the billions of microbial lives I have erased from the earth these past 25 years, my next life is not going to be so pleasant. I will probably come back as a rabbit in a syphilis lab.
It is always fun when my hobby, writing for SBM, crosses paths with my job. This month the Annals of Internal Medicine published “Oseltamivir Compared With the Chinese Traditional Therapy Maxingshigan–Yinqiaosan in the Treatment of H1N1 Influenza. A Randomized Trial.”
I though big pharma was good at coming up with names I do not know how to pronounce. If someone could provide a pronunciation guide in the comments, it would be ever so helpful, so I will not have to embarrass myself when this entry becomes a Quackcast. Dr. Hall wrote about this article on Tuesday, and I have avoided reading her post until this one is up, so there may be overlap in what is discussed. (more…)
About three weeks ago, ironically enough, right around the time of TAM 9, the New England Journal of Medicine (NEJM) inadvertently provided us in the form of a new study on asthma and placebo effects not only material for our discussion panel on placebo effects but material for multiple posts, including one by me, one by Kimball Atwood, and one by Peter Lipson, the latter two of whom tried to point out that the sorts of uses of these results could result in patients dying. Meanwhile, Mark Crislip, in his ever-inimitable fashion, discussed the study as well, using it to liken complementary and alternative medicine (CAM) as the “beer goggles of medicine,” a line I totally plan on stealing. The study itself, we all agreed, was actually pretty well done. What it showed is that in asthma a patient’s subjective assessment of how well he’s doing is a poor guide to how well his lungs are actually doing from an objective, functional standpoint. For the most part, the authors came to this conclusion as well, although their hedging and hawing over their results made almost palpable their disappointment that their chosen placebos utterly failed to produce anything resembling an objective response improving lung function as measured by changes (or lack thereof) in FEV1.
In actuality, where most of our criticism landed, and landed hard—deservedly, in my opinion—was on the accompanying editorial, written by Dr. Daniel Moerman, an emeritus professor of anthropology at the University of Michigan-Dearborn. There was a time when I thought that anthropologists might have a lot to tell us about how we practice medicine, and maybe they actually do. Unfortunately, my opinion in this matter has been considerably soured by much of what I’ve read when anthropologists try to dabble in medicine. Recently, I became aware that Moerman appeared on the Clinical Conversations podcast around the time his editorial was published, and, even though the podcast is less than 18 minutes long, Moerman’s appearance in the podcast provides a rich vein of material to mine regarding what, exactly, placebo effects are or are not, not to mention evidence that Dr. Moerman appears to like to make like Humpty-Dumpty in this passage: