There’s been a lot of discussion, both in the scientific literature and online, about recent pertussis outbreaks, which are the worst outbreaks in the US in the last 50 years. How could this possibly be, it is asked, when vaccine uptake for the pertussis vaccine remains high? True, there are pockets of vaccine resistance, where uptake of the vaccine is low, but it’s becoming increasingly clear that, unlike the case of measles outbreaks, low uptake of the pertussis vaccine does not appear to be nearly enough to explain the frequency and magnitude of the outbreaks. Given that it’s been a while since any of us has discussed the recent pertussis outbreak here on SBM, I thought that it would be a good time for me to do so, particularly because there have been some new studies and new developments since April, including a paper hot off the presses last Thursday in the New England Journal of Medicine. As a result, those of you who read me at my not-so-super-secret other blogging location might find some of the material in this post familiar, but given the new NEJM paper, I thought that now would be a good time to synthesize and update what I’ve discussed before in different forums in a more comprehensive way, even at the risk of some repetition of previous material I’ve published elsewhere. Hopefully, it will also provide materials for skeptics and supporters of SBM to counter the antivaccine movement, which has pounced on the recent pertussis outbreaks as evidence that the “vaccine doesn’t work.”
Without a doubt (to me, at least), the biggest difference between science-based doctors and quacks is a very simple one. When a treatment or preventative measure isn’t working as well as it should, we science-based physicians ask why. We try to find out what is not working optimally and why. Then we try to figure out how to make things better. So it is with the acellular pertussis vaccine. This vaccine protects against whooping cough, which is caused by Bordetella pertussis, and is administered to children in the form of a combination vaccine, the DTaP (diptheria/tetanus/acellular pertussis). Five doses are recommended for children, the first at age 2 months, and then at ages 4 months, 6 months, 15-18 months, and 4-6 years. There is also the newer formulation, the Tdap (tetanus, diptheria, and acellular pertussis), which is recommended for people between the ages of 11 and 64. The Tdap is now usually administered first at age 11-12, with additional recommendations for a Tdap booster in adolescents and adults summarized here, here, and here. Unfortunately, although the vaccine works, recent outbreaks have suggested that we need to change our approach to pertussis vaccination. Let’s see why.
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.
[Editor’s note: It’s a holiday here in the U.S.; consequently, here is a “rerun” from my other super not-so-secret other blog. It’s not a complete rerun. I’ve tweaked it a bit. If you don’t read my other blog, it’s new to you. If you do, it’s partially new to you. See you all next week with brand spankin’ new material. It also (Ih hope) complement’s Scott’s excellent post from Thursday discussing the same issue and the same paper, but from a different perspective.]
As a cancer surgeon specializing in breast cancer, I have a particularly intense dislike reserved for cancer quacks, which I have a hard time containing at times when I see instances of such quackery applied to women with breast cancer. I make no apologies. These women are, after all, the type of patients I spend all my clinical time taking care of and to whose disease my research has been directed for the last 13 years or so. That’s why I keep revisiting the topic time and time again. Unfortunately, over the years, when it comes to this topic there’s been a depressing amount of blogging material. Indeed, Scott Gavura took a bite out of this particularly rotten apple just a few days ago. Even though he handled the discussion quite well, I thought it would be worthwhile for a breast cancer clinician to take a look. Our perspectives are, after all, different, and this is an issue that, from my perpective, almost can’t be discussed too often.
One question that comes up again and again is, “What’s the harm?” Basically, this question boils down to asking what, specifically, is the downside of choosing quackery over science-based medicine. In the case of breast cancer, the answer is: plenty. The price of foregoing effective therapy can be death; that almost goes without saying. In fact, it can be a horrific and painful death. It is, after all, cancer that we’re talking about. Aside from that, however, the question frequently comes up just how much a woman decreases her odds of survival by avoiding conventional therapy and choosing quackery. It’s actually a pretty hard question to answer. The reason is simple. It’s a very difficult topic to study because we as physicians have ethics. We can’t do a randomized trial assigning women to treatment or no treatment, treatment or quacke treatment, and then see which group lives longer and by how much. If a person can’t see how unethical that would be without my having to explain it, that person is probably beyond explanations. (As an aside, I can’t help but point out that a randomized trial of not vaccinating versus vaccinating is unethical for exactly the same reason; physicians can’t knowingly assign subjects to a group where he knows they will suffer harm. There has to be clinical equipoise.) There’s no doubt that foregoing effective treatment causes great harm.
There is something in molecular biology and genetics known as the “central dogma.” I must admit, I’ve always hated the use of the word “dogma” associated with science, but no less a luminary than Francis Crick first stated it in 1958, and it has been restated over the years in various ways. Perhaps my favorite version of the central dogma was succinctly stated by Marshall Nirenberg, who said, “DNA makes RNA makes protein,” which about sums up all of molecular biology in five words. Or at least it did until the last ten or twenty years, when we’ve been finding exceptions to this dogma.
I don’t want to dwell on the central dogma. As I’ve said, I loathe the use of the term “dogma” to describe anything in science, although a discussion of the central dogma and its exceptions might make for a decent post one day. What brought the central dogma to mind is a series of articles I saw recently in ONCOLOGY: Perspectives on Best Practices that let me to ponder the question: What is the “central dogma” of “alternative medicine”? I realize that alt-med is an unwieldy gmish of ideas that range from the semi-plausible but unproven to the completely ridiculous (i.e., homeopathy or reiki), but after reading these articles and thinking about it, I do believe that there is in actuality a “central dogma” of alternative medicine. I also believe that it is entirely appropriate to call it a “dogma” in this situation, because it is far more a matter of faith than it is of science. Moreover, the more that quackademic medicine infiltrates academic medicine, the more this “central dogma” has infiltrated academic medicine with it. Indeed, as you will see, when this central dogma is questioned, even by someone sympathetic to “complementary and alternative medicine” (CAM; i.e., “complementing” medicine with quackery) or “integrative medicine” (i.e., the “integration” of pseudoscientific medicine with medicine).
There are certain topics in Science-Based Medicine (or, in this case, considering the difference between SBM and quackery) that keep recurring over and over. One of these, which is of particular interest to me because I am a cancer surgeon specializing in breast cancer, is the issue of alternative medicine use for cancer therapy. Yesterday, I posted a link to an interview that I did for Uprising Radio that aired on KPFK 90.7 Los Angeles. My original intent was to do a followup post about how that interview came about and to discuss the Gerson therapy, a particularly pernicious and persistent form of quackery. However, it occurred to me as I began to write the article that it would be better to wait a week. The reason is that part of how this interview came about involved three movies, one of which I’ve seen and reviewed before, two of which I have not. In other words, there appears to be a concerted effort to promote the Gerson therapy more than ever before, and it seems to be bearing fruit. In order to give you, our readers, the best discussion possible, I felt it was essential to watch the other two movies. So discussion of the Gerson protocol will have to wait a week or two.
In the meantime, there’s something else that’s been eating me. Whether it’s confirmation bias or something else, whenever something’s been bugging me it’s usually not long before I find a paper or online source to discuss it. In this case, it’s the issue of why scientific studies are reported so badly in the press. It’s a common theme, one that’s popped upon SBM time and time again. Why are medical and scientific studies reported so badly in the lay press? Some would argue that it has something to do with the decline of old-fashioned dead tree media. With content all moving online and newspapers, magazines, and other media are struggling to find a way to provide content (which Internet users have come to expect to be free online) and still make a profit. The result has been the decline of specialized journalists, such as science and medical writers. That’s too easy of an answer, though. As is usually the case, things are a bit more complicated. More importantly, we in academia need to take our share of the blame. A few months ago, Lisa Schwartz and colleagues (the same Lisa Schwartz who with Steven Woloshin at Dartmouth University co-authored an editorial criticizing the Susan G. Komen Foundation for having used an inappropriate measure in one of its ads) actually attempted to look at how much we as an academic community might be responsible for bad reporting of new scientific findings by examining the relationship between the quality of press releases issued by medical journals to describe research findings by their physicians and scientists and the subsequent media reports of those very same findings. The CliffsNotes version of their findings is that we have a problem in academia, and our hands are not entirely clean of the taint of misleading and exaggerated reporting. The version as reported by Schwartz et al in their article published in BMJ entitled Influence of medical journal press releases on the quality of associated newspaper coverage: retrospective cohort study. It’s an article I can’t believe I missed when it came out earlier this year.
Every so often I get requests to be interviewed on the radio about skeptical topics. Now, why anyone would ever want to interview me, who knows? But they do, and when I can manage to accommodate reporters or interviewers, I do. Last week, I was interviewed on Uprising Radio, in which I discussed alternative medicine (particularly the Gerson therapy for cancer). My segment is around 10 or 15 minutes, and I invite SBM readers to take a listen. I’m afraid I might have been a bit “strident” in my dismissal of various bits of quackery for some. Whether I was too “strident” or not, the interview request came about in response to another radio personality on the same radio station shilling for the Gerson therapy, which reminds me. Perhaps I should revisit Max Gerson; for some reason there appears to be a flurry of promotion of that hoary old quackery. Stay tuned on Monday to see if that’s what I decide to blog about.
One issue that keeps coming up time and time again for me is the issue of screening for cancer. Because I’m primarily a breast cancer surgeon in my clinical life, that means mammography, although many of the same issues come up time and time again in discussions of using prostate-specific antigen (PSA) screening for prostate cancer. Over time, my position regarding how to screen and when to screen has vacillated—er, um, evolved, yeah, that’s it—in response to new evidence, although the core, including my conclusion that women should definitely be screened beginning at age 50 and that it’s probably also a good idea to begin at age 40 but less frequently during that decade, has never changed. What does change is how strongly I feel about screening before 50.
My changes in emphasis and conclusions regarding screening mammography derive from my reading of the latest scientific and clinical evidence, but it’s more than just evidence that is in play here. Mammography, perhaps more than screening for any disease, is affected by more than just science. Policies regarding mammographic screening are also based on value judgments, politics, and awareness and advocacy campaigns going back decades. To some extent, this is true of many common diseases (i.e., that whether and how to screen for them are about more than just science), but in breast cancer arguably these issues are more intense. Add to that the seemingly eternal conflict between science and medicine communication, in which a simple message, repeated over and over, is required to get through, versus the messy science that tells us that the benefits of mammography are confounded by issues such as lead time and length bias that make it difficult indeed to tell if mammography—or any screening test for cancer, for that matter—saves lives and, if it does, how many. Part of the problem is that mammography tends to detect preferentially the very tumors that are less likely to be deadly, and it’s not surprising that periodically what I like to call the “mammography wars” heat up. This is not a new issue, but rather a controversy that flares up periodically. Usually this is a good thing.
And these wars just just heated up a little bit again late last week.
Dying of cancer can be a horrible way to go, but as a cancer specialist I sometimes forget that there are diseases that are equally, if not more, horrible. One that always comes to mind is amyotropic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease. It is a motor neuron disease whose clinical course is characterized by progressive weakness, muscle atrophy and spasticity, with ultimate progression to respiratory muscles leading to difficulty breathing and speaking (dysarthria) and to the muscles controlling swallowing. The rate of clinical course is variable, often beginning with muscle twitching in an arm or a leg or slurring of speech. Ultimately, however, ALS progresses to the loss of ability to move, speak, eat, or breathe. The most common cause of death is from respiratory failure, usually within three to five years after diagnosis, although there is the occasional outlier with a less malignant form of the disease with a slower course of progression who can live a long time, such as Steven Hawking.
In other words, ALS is a lot like cancer in some ways. It is a progressive, fatal disease that usually kills within a few years at most. On the other hand, it is different from cancer in that, at least for many cancers we actually do have effective treatments that prolong life, in some cases indefinitely. In contrast the most effective treatment we currently have for ALS is a drug (riluzole) that is not particularly effective—it prolongs life by months—and can be best described as better than nothing, but not by a whole lot. So it is not surprising that ALS patients, like cancer patients, become desperate and willing to try anything. This is completely understandable, but sometimes this desperation leads to activities that are far more likely to do harm than good. I was reminded of this when I came across a post in the antivaccine propaganda blog, Age of Autism, referring to an article in The Scientist entitled Medical Mavericks. The fortuitous posting of this story, which was apparently designed to try to show that it’s not as crazy as critics have said to be treating autistic children with “Miracle Mineral Solution” (MMS) (which is a bleach) given that the introduction explicitly mentioned Kerri Rivera and the patient described in the article used sodium chlorite to treat his ALS, provided me the opening to discuss a group whose existence and advocacy brings up a complex tangle of issues that boil down to questions of how far patient autonomy should be allowed to go. I’m referring to a company, PatientsLikeMe, which describes itself thusly:
“Targeted therapy.” It’s the holy grail of cancer research these days. If you listen to its most vocal proponents, it’s the path towards “personalized medicine” that improves survival with much lower toxicity. With the advent of the revolution in genomics that has transformed cancer research over the last decade, including the petabytes of sequence and gene expression data that pour out of universities and research institutes, the promise of one day being able to a patient’s tumor, determining the specific derangements in genome and gene expression that drive its uncontrolled proliferation, and finding drugs to target these abnormalities seems more tantalizingly close than ever. Indeed, it seems so close that even dubious practitioners, such as Stanislaw Burzynski, have jumped on the bandwagon, co-opting the terms used by real oncologists and real cancer researchers to sell “personalized gene-targeted cancer therapy,” which in their hands are really no more than a parody of efforts to synthesize the enormous quantity of genomic data each patient’s tumor possesses and figure out how best to take advantage of it, a “personalized genomic therapy for dummies,” if you will.
That’s not to say that there aren’t roadblocks to realizing this vision. The problems to be overcome are substantial, and I’ve discussed them multiple times before. For example, just a couple of weeks ago I discussed an example of just what it takes to apply these new genomic techniques to an individual patient. The resources required are staggering, and, more problematic, there often aren’t any single “magic bullet” molecular pathways identified that can be targeted with existing drugs. The case I discussed was a fortunate man indeed in that such a pathway was identified, but most tumors are driven by many derangements in growth control, metabolism, migration, and the other hallmarks of malignancy described by Robert Weinberg. Worse, in many cases we don’t even have drugs that can attack many of the abnormalities that drive cancer progression. Then there’s the issue of tumor heterogeneity, which comes about because cancer is as good example of a disease as I can think of in which evolution due to natural selection results in incredible differences in the cancer cells in one part of the tumor compared to other parts of the tumor or in the tumor metastases. A “targeted” therapy that targets the genetic abnormalities in one part of the cancer might well fail to target the genetic abnormalities driving another part of the tumor.
These, and many other reasons, are why we haven’t “cured cancer” yet.