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I had originally planned on writing about a different topic today, but, as is so often the case in blogging, something came up that caught my attention, much as the errant thought of a squirrel distracts Dug the Dog. It’s no big deal. My original topic is not time-sensitive, and I’ll get to it next week (that is, unless something like this happens again). In any case, my tendency towards blogging ADHD notwithstanding, the “inspiration” for this post began on Friday morning, making it timely. Let me tell you what happened, and then I’ll delve into the topic.

We all have our daily rituals, and I’m no different. When I wake up in the morning, I usually check my iPhone to see how many e-mails I’ve gotten overnight. If there’s time before I have to leave for work, I’ll frequently go through them all right then, answering ones I can answer quickly and filing for later responses those that I can’t. If I don’t have time (as in I overslept), I’ll check them whenever I get an opportunity. Last Friday, I was rather surprised to see that the little badge on the Mail app showed well over three times the usual number of messages I get overnight, even accounting for e-mail notifications of comments on the blogs and the usual smattering of mailing list messages and the odd junk spam that got through the filters. So having that many messages in my unread mail queue caught my attention. Even when a new troll shows up in the comments of one of the blogs, I usually don’t get that many notifications. I figured I’d better go and check to see what was going on right then, rather than waiting until later. What I found was something that I never would have guessed.

As odd as it seems to me now, I had apparently been targeted by a Change.org petition Animal Experimenters – JUSTIFY YOUR SCIENCE CLAIMS.

I was rather puzzled. I’ve developed a bit of microcelebrity (or, as I sometimes refer to it when I’m feeling less arrogant, nanocelebrity) as the proverbial proponent of science-based medicine and scourge of quackery. When it comes to topics that are likely to result in a backlash against me by cranks, to the few thousand people who read my stuff, both here and on my not-so-secret other blog, I’m known not so much for my defense of animal research (although I do from time to time write to defend it and to castigate animal rights extremists who threaten scientists) as for writing about the antivaccine movement, cancer quackery, and other forms of pseudoscience. For instance, antivaccinationists have tried to get me fired from my job. Over the years, cancer quacks have harassed me at work, tried to get me fired, and threatened me with lawsuits. More recently, a supporter of Stanislaw Burzynski complained to my cancer center director and the president of my practice plan about my activism with respect to the Burzynski Clinic. I’ve even been the victim of a frivolous complaint against me to the Michigan Board of Medicine by (I’m 95% sure) a Burzynski patient who didn’t like my analysis of her case. The complaint was promptly found to be groundless, but there is a complaint on my record nonetheless. These are the usual sources of criticism against me, not animal rights activists. None of this is to say that animal rights activists don’t occasionally attack me. Ray Greek, for instance, most definitely did not like it the last time I criticized him on this blog, but that was almost six years ago, ancient history in blog time, and the last time I launched a broadside at animal rights activists on this blog was in 2008.

That is not saying I haven’t been vocal speaking out against animal rights activists and how they negatively impact biomedical research, but it’s only been sporadically at my not-so-secret other blog. In particular, I’ve made it a point to speak out against a group known as Negotiation Is Over, a group led by a truly scary woman named Camille Marino, who recently got involved in a legal kerfuffle over her activities against a researcher at my home institution that led to her serving a term in prison, from which she was recently released. (She’s also a woman who has made it clear that she is intentionally targeting students as the “soft underbelly of the vivisectionist movement” and has no compunction about justifying violence against researchers, similar to the way that Steve Best does, which is why it’s so ironic that Best is not so happy now that Marino has turned her tactics against him.) It’s just that it’s by far nowhere near the top of the list of my usual topics, which made me honored but at the same time puzzled that I am mentioned in the petition with so many much more accomplished scientists than I. Moreover, I was even more puzzled at being included on this list given that the petition was clearly aimed at the government of the UK, asking MPs to support something called EDM 263, which appears to be a call for public debates on the use of animals in research. Unfortunately, the game is revealed by the way this appeal is described:

Please use our template letter and follow the STEPS 1 – 4 to ask your MP to sign EDM 263, calling for scientists from the vivisection community to agree to participate in properly moderated public scientific debates with leading medical experts who oppose animal experiments on human medical and scientific grounds.

Whenever you see the word “vivisectionist” to describe researchers who do animal research, you can be quite sure that you’re not dealing with people with reasonable questions about how animals are used in research. Real scientists almost never use the term “vivisection” because, although it has taken on a broader meaning with respect to animal research, based on the history of the use of the word, “vivisection” still implies surgery conducted for experimental purposes on living animals to view living internal structures; i.e., dissection of living animals. These days, virtually no animal experimentation can be accurately referred to as “vivisection,” as strict rules and regulations mandate minimization of pain and suffering. Animal rights activists tend to like to refer to all animal research, whether it involves surgery or not, as “vivisection” and to scientists who use animals in their experiments as “vivisectionists” because of the negative connotation of the word. That’s why the word “vivisectionist” is rarely used by scientists but is frequently used by animal rights activists and why use of the word “vivisectionist” is as reliable a tipoff as there is to identify an animal rights activist, every bit as useful as “dis-ease” or “out-fection” instead of “disease” or “infection,” as very reliable signs of a quack or supporter of quackery.

I’ll get back to the group behind this petition in a moment, which is known as For Life On Earth (FLOE). First I’d like to address the petition itself and its demand for a “debate,” after which I’ll discuss the actual claimed science arguing against animal research a bit and then finish by coming back to this group. As a prelude, however, let me point out that I won’t be dealing (much) with the morality of animal research, mainly because I believe that whether or not animal research is morally acceptable is not primarily a scientific question. Science can inform the consideration of the question of animal research, but in the end it’s a moral question. That is not to say that science is irrelevant, because part of the consideration of the moral question of whether and when it is acceptable to use animals in research is the issue of how much value to science animal research brings. How utilitarian you want to be considering this question is something that can be discussed, but animal rights activists often invoke an extreme negative version of a utilitarian argument in that they try to portray as animal research as not just useless (i.e., providing no useful scientific information), but even as harmful or providing misleading or mistaken scientific conclusions. If that is the case, then it’s a no-brainer that animal research cannot be justified ever because in that case it would cause suffering to animals but provide no benefit in terms of scientific advancements that could lead to improved medical care. Unfortunately, as I documented six years ago, animal rights activists have a distressing tendency to use truly bad arguments to do everything they can to paint animal research as useless or even harmful to the science of medicine. These arguments tend to fall into one or more of three categories:

Animal research doesn’t teach us anything of value or even misleads us (i.e., it is bad science). Animal research does not predict human physiology or response to disease, or animals are “just too different from humans to give reliable results” (i.e., it is bad science). There are better ways of getting the information that do not use animals (i.e., there is better science available than using animals.)

As I’ve said on several occasions, I tend to look at these arguments as three facets of what is in essence the same argument, specifically what I like to call an “argument from imperfection” also known as the Nirvana fallacy. In other words, because animal models have imperfections and all-too-often don’t predict human physiology or drug response as well as the critics think that they should, then by implication all animal research is bad science. It is an example of demanding 100% perfection or certainty before accepting something, a bar that no science can ever meet, and of concrete thinking typical of extremists. Antivaccinationists are particularly fond of this sort of concrete thinking, in which vaccines must be 100% effective in preventing disease and 100% safe, or they are worthless.

Like the case with many holding dubious scientific beliefs whom many would consider cranks, one favorite tool to promote their agenda is “public debate.” I’ve seen it many times myself. For example, I’ve had HIV denialists and antivaccine activists challenge me to “live” public debates over their favorite topics. This challenge through a Change.org petition is no different. In fact, it’s a perfect example of a principle that I’ve called “all truth comes from live public debate.” Besides the challenges I’ve personally had directed at me, I can point to several more examples just off the top of my head. For example, antivaccine guru Andrew Wakefield challenged Dr. David Salisbury to a “live public debate” about whether the MMR vaccine causes autism or not. (Hint to Wakefield: It doesn’t.) Regular readers might also remember another example, Suzanne Somers’ doctor, antivaccinationist, and all around supporter of all things quacking, Julian Whitaker, debating Steve Novella at FreedomFest, which happened to be going on in Las Vegas at the same time as TAM in 2012; Michael Shermer’s “debate” with Deepak Chopra; and antivaccine propagandist David Kirby debating author Arthur Allen. More recently, a fan of Stanislaw Burzynski named Randy Hinton was “calling out” what he referred to as the “medical mafia” to debate. Still more recently, Bill Nye the Science Guy has foolishly (in my opinion) agreed to a “debate” about creationism and evolution with arch-creationist Ken Ham. The debate will be held tomorrow. Worse, he agreed to do it on Ham’s home turf, the Creation Museum in Kentucky.

Basically, this petition demonstrates once again the “all truth comes from live public debate” belief so prevalent among cranks. I’ll call it the omne verum est a forensem principle. (Latin sounds so much more cool for this, but I have no idea whether this is the best translation—or even grammatically correct; maybe Latin scholars out there can suggest better.) They seem to think that science is decided in public debates and view the quite understandable reluctance among scientists like myself and skeptics to engage cranks in such spectacles as “cowardice.” It is not, but cranks continue to labor under the delusion that science is somehow decided in such forums, which are a variant of a sort of argumentum ad populum, in which something is argued to be true because it is popular or, in a debate, an argument is thought to be closer to the truth because it is more popular. Science doesn’t work that way. It is decided on evidence presented at scientific conferences and in peer-reviewed journals, where the real scientific debate plays out until it is temporarily settled and scientists come to a provisional consensus. That provisional consensus, of course, is always subject to change as new observations, data, and experimental results come to light, but it takes observations, data, and experimental results to change the consensus, not “live public debates.” Such “live public debates” have only one purpose: To sway public opinion to a viewpoint not supported by science, in the process elevating pseudoscience or the unproven to the same plain as the scientific consensus as a scientifically viable “alternative,” no more, no less.

The fact is, pseudoscientists, pseudohistorians, and cranks desperately want to debate accepted experts in the field in which they apply their crankery. The reason is simple. While, knowingly (or, more commonly, unknowingly) they poo-poo science and the scientific method, at the same time they desperately crave its validation. They desperately want to be seen as “one of the boys,” whose ideas are worthy of being taken seriously by scientists, and such “debates” usually give them exactly what they want. Indeed, debates on college campuses (or, in the case of homeopaths, in academic medical centers) are not viewed as a means of getting at the truth, but rather as a means of P.R. Putting the pseudoscientist on the same stage as a legitimate scientist elevates the pseudoscientist unduly and mistakenly gives the impression to lay people that there is a genuine scientific controversy to be debated when the only controversy being debated is, in fact, ideological. This is because getting a scientist to agree to a debate allows them to portray their pseudoscience as being on equal footing with accepted science, or at least in the same ballpark. Thus, simply being seen on the same stage on an equal footing with a respected scientist, is a victory for the pseudoscientist. Regardless of what actually happens in the debate, it is a virtual certainty that the crank and the supporters of crankery will trumpet it as a “victory” or, at the very minimum, as a “validation” that science is beginning to take them seriously.

If animal rights activists—or antivaccinationists, purveyors of “alternative medicine,” HIV/AIDS denialists, creationists, 9/11 Truthers, or the like—want to convince scientists, there is one way to do so: Publish their data and do battle where scientists normally do battle, in the scientific literature and in scientific conferences. “Live public debates” might sway a few souls when the odd hapless scientist or skeptic unprepared for the Gish gallop makes the mistake of going up against a smooth talking crank, but the scientific consensus remains unchanged. I realize that not all skeptics agree with me, and I find it hard to be critical of Steven Novella, Michael Shermer, or even Bill Nye for feeling duty-bound to answer the call.

In the case of animal rights activists, the call for public debates is similarly dubious, as becomes obvious from some of the verbiage in the petition:

By signing this petition, your letter will automatically be sent to high profile animal experimenters and their supportive colleagues, inviting them to go head to head in properly moderated, public scientific debates with the world’s leading medical experts who oppose animal experiments, purely on human medical and scientific grounds – namely that misapplying results from animal experiments, to try and ‘predict’ human responses, causes immense harm to human patients. Current understanding of evolutionary biology is now able to explain why this is the case.

If you note the two links, you’ll see that both of them are pretty much rehashes of Ray Greek’s arguments, which were not particularly convincing to me the first time around and haven’t gotten any better with age. One of them is a video produced by FLOE:

Particularly irrelevant is the way the argument begins with a reference to Claude Bernard in 1847 as the man who allegedly “institutionalized” animal research as being “predictive” of human responses. Yes, I’m always convinced by an appeal to a 167-year-old understanding of science by one man, who rejected the theory of evolution and apparently believed that experiments on animals were “entirely conclusive for the toxicology and hygiene of man.” One wonders whether science has advanced since 1847. Apparently, FLOE simultaneously doesn’t think so and does. At one point, it is argued that animal testing hasn’t advanced since then, but then at another point, the discoveries of Ignaz Semmelweis, Joseph Lister, John Snow, Edward Jenner, Charles Darwin, and Albert Einstein (whose relevance to the science of animal research is never explained) are briefly mentioned, after which FLOE fast forwards 100 years to 2009 to Ray Greek’s book Animal Models in the Light of Evolution , whose image appears as the narrator intones that science brings us complexity theory. Particularly insulting to one’s intelligence is how it’s intoned that animal models predict human responses only 31% of the time. What responses? What animal models? Animal models vary widely in how well they predict human responses, depending on the physiological response, the specific animal model, the drug, and the process being studied. To lump them all together into a figure like this is well-nigh meaningless.

A good way to think of it comes from this recent review of animal models for predicting immune responses:

Besides the animal model itself, the experimental setup will also affect predictive value. Differences in dose, immunization route, frequency of administration and impurities in the formulation have the potential to affect immunogenicity and its assessment (32). Moreover, with respect to product quality, preclinical protein products which are used in animal studies do not always reflect the final products used to treat patients. Another difficulty in translating animal results to human patients is a difference between labs in antibody assays that are used. These differences hamper comparison of results gained in different labs and therefore compromise predictive value of animal models. In patient research, several initiatives have begun to standardize antibody assays and thus improve comparability (34). Adjusting the antibody assays used in animal research to these standardized assays would likely improve predictive value of the models.

The video cited in the FLOE petition then compares the predictive value generally required of clinical laboratory tests, which is stated to be 90%, a coin flip (50%), and the purported predictive value for animal tests for human response (31%). Even if 31% is an accurate estimate, do you see the problem with this argument? There is a huge difference between a test that is going to be used on humans to make a diagnosis (like a CT scan or blood test) and a test that is often being used to screen for a response (animal studies). Anyone who says something like this has no clue how clinical medicine works. There are lots of tests in routine use whose predictive value is less than 90%, sometimes considerably less than 90%. Examples include mammography for breast cancer. Only around 25% of those found to have suspicious lesions on mammography actually turn out to have breast cancer.

One point that I find rather odd is how FLOE emphasizes that the medical experts it wants to be part of these debates accept the last seven out of nine uses of animals in research:

Animals as models for disease Animals as test subjects; e.g. drug testing Animals as spare parts Animals as factories Animal tissue to study basic physiological principles Animals for dissection in education Animals as a modality for ideas (heuristic) To benefit other animals Knowledge for knowledge sake

It is only the first two that FLOE claims to be contesting, although it can’t resist mentioning that “for these viable methods there already exist some more efficient, less expensive, human biology based alternatives.” Don’t believe it. Focusing on the first two is the thin edge of the wedge for animal rights activists to go after the last seven.

So what is EDM 263? This is its text:

That this House notes the new campaign For Life On Earth which is critical of avoidable experiments on animals; is alarmed that all studies measuring the claimed ability of animals to predict human responses expose a low success rate in the region of 31 per cent; further notes that a success rate in the region of 90 per cent is required by medical practice; further notes that the National Cancer Institute has said that cures for cancer have been lost because studies in rodents have been believed; and calls for properly moderated scientific public debates on the misleading results and bad science of animal experiments.

Again, the use of this 31% figure in comparison to an alleged 90% figure for medical tests is an utter insult to the intelligence of any physician who knows about medical testing for the reasons I mentioned above, but it sure sounds plausible to people who don’t know about the science of medical testing. It didn’t take me long to find out that the source of the claim that the NCI has said that cures have been lost due to too much trust in rodent models is misleading as well. it comes from a 1997 article in Science :

Pharmaceutical companies often test drug candidates in animals carrying transplanted human tumors, a model called a xenograft. But not only have very few of the drugs that showed anticancer activity in xenografts made it into the clinic, a recent study conducted at the National Cancer Institute (NCI) also suggests that the xenograft models miss effective drugs. The animals apparently do not handle the drugs exactly the way the human body does. And attempts to use human cells in culture don’t seem to be faring any better, partly because cell culture provides no information about whether a drug will make it to the tumor sites.

The whole point of the article was that back in 1997 none of the common methods used to screen potential new anticancer drugs for activity—animal, cell culture, or other—had been sufficiently effective in identifying anticancer activity. The entire article was a cry for better methods. Over the last 17 years, a lot of effort has gone into doing this, both using animals and not. For example, mouse avatars are an innovative idea that might have real promise for predictive modeling for individual patients. I’ve written about them before. (If that worked out, wouldn’t that burn FLOE?) Moreover, the NCI, far from saying that animal research is useless, maintains a website that provides information on animal models, when they are useful, and for what purposes. Make no mistake, mouse models have been very useful indeed.

Let’s come back to that 31% figure. As you can tell, it bugs me, but not for the reasons that Ray Greek, for example, might think (namely, that it is such a damning indictment of animal research). It just smells so…fishy. Greek frequently uses it in his talking points and articles, and FLOE flogs it endlessly in its video and on its website. Where did it come from? Speaking of Research tells me! It’s worth going there for the details, but I’ll feed you the summary:

Our ‘region of 31%’, then, is based on a “very approximate estimate” of one small aspect of animal research, by a Department of Health doctor in 1978 based on 45 drugs that happened to have been licenced in the last year. Not only does the paper conclude that animal experiments correlate to human reactions, in terms of prediction it was a generation ago, it was a different regulatory environment, it was based on a 35-year old understanding of toxicology, it had a sample size of 45 and it was a rough analysis. The claim that this paper shows that animal studies have a “low success rate of 31%’” is simply pseudoscience.

As is so common with these sorts of arguments, animal rights activists misconstrue animal testing as animal research. This particular animal rights activist has used a cherry-picked number, a guessed percentage, that was based on an incorrect interpretation of a paper from more than 35 years ago. Based on this, and dubious claims of “harm” from animal research, FLOE demands not just that animal models be phased out, but rather eliminated immediately. I kid you not.

And what, you ask, will replace them? Good question. I’m still asking that myself. All we get are vague references to “complexity” theory and all sorts of fancy gobbledygook about evolution and genetics that do not make the point that FLOE is trying to make. For instance, it is stated that we should study the genetic variation between humans, which can convey medical data. Wow. So brilliant! It’s not as though medical researchers would ever have thought of that on their own. Oh, wait…they have! It goes under various names: personalized medicine, highly stratified medicine, genomic medicine. It’s not as though medical researchers haven’t been doing this for more than a decade, ever since the development of cDNA microarrays allowed the simultaneous analysis of the expression of every gene on a cDNA microarray chip. The movement has accelerated now that next generation sequencing techniques are becoming widely available. It’s not an either-or proposition. We can continue to exploit advances in genomic medicine while retaining and improving upon animal models that have proven useful. What FLOE is promoting is a false dichotomy: Animal research or genomic medicine, as if we can’t do both. Moreover, animal research informs personalized medicine; the mouse avatars I mentioned were just one example of how. Just consider the example of Herceptin if you don’t believe that.

The video concludes with a list of the “many valid research methods” that don’t use animals. These include in vitro studies of human tissue, which we already do; epidemiology, which we already do; the study of bacteria, viruses, and fungi, which we already do; autopsy and cadaver studies, which we already do; genetic research, which we already do; clinical research, which we already do; and post-marketing drug surveillance, which we already do. Indeed, as the video concluded, I really wondered what the point was. We already do all those forms of research. Seriously. The words of the great Robert Weinberg come to mind:

Dr. Greek says the silliest things, […] implying that people are not studying human tumors, and implying that the kinds of experiments that one can do in mice can be done as well in humans — truly mindless!

The sheer oversimplification of complex issues made me wonder what FLOE is. It appears to be a propaganda group to promote Ray Greek’s ideas. The petition demanding a “debate” is nothing more than the typical crank ploy whose basis is a mistaken belief that all truth comes from public debate. Although I’m quite honored to be included on the list of scientists who are being challenged to debate the issue, I must politely decline.

The utility of animal research for medical advancement is a legitimate topic to discuss, but the discussion would not be furthered by a public debate of the sort proposed by FLOE. It is a question that is already being debated by scientists and ethicists in the medical literature based on actual data and science rather than dubious arguments. Moreover, the use of animals in research is already being de-emphasized. Regulations mandating the “three Rs” (reduction, refinement, replacement) are already in force and having an effect. The morality of animal research is a question that can’t be answered just by science, but science sure can refute the claims of animal rights activists that animal research provides no knowledge and benefit to medical science.