I have two brief observations to make before I launch into my latest bit of insolence. First off, it figures that, whenever I go away to a meeting, there’s simply an embarrassment of blogging riches. People have been sending me stuff to which, even if I were at home and having a slow week, I could probably never get. Good stuff. Interesting stuff. Unfortunately, I’m now forced either to try to blog about them when I finally get home, which might as well be months later in blog-time, or let them go by uncommented upon, which hurts Orac’s mighty ego. Oh, well. My next observation is that I feel a bit queasy taking on this next topic, but it’s very important. The reason I feel a bit queasy is because the person writing the piece to which some insolence, both respectful and not-so-respectful, must be applied is almost certainly going to die of leukemia, and I hate to be perceived as kicking a person who’s dying.
The problem is, she’s an animal rights activist, and she’s trying to justify her hypocrisy of having taken treatments for her cancer that had been tested by spreading the same misinformation about animal research that animal rights are known for spreading far and wide. Dying or not, she needs to be called out for spreading falsehoods. Her name is Simon Chaitowitz, and she is the former Communications director for the animal rights group masquerading as a legitimate physicians’ group, the Physicians Committee for Responsible Medicine, a crank organization dedicated to eliminating animal research that has had as one of its luminaries the apologist for animal rights terrorism, Jerry Vlasak. Her article is entitled Why I Take Animal-Tested Drugs, and was posted both to–where else?–The Huffington Post and to Common Dreams. The article is incredibly odious because in essence it argues that she is dying because she took animal-tested drugs, not because she was unfortunate enough to develop breast cancer, then develop complications from the chemotherapy, and then develop leukemia. She is, in essence, arguing that she might not be dying if she hadn’t done what she had done, that a cure might have been found for her condition already if scientists didn’t use animal models so widely.
Before Ms. Chaitowitz proceeds to the big lie, she starts out with on only slightly smaller lie:
The truth — mostly hidden from public view — is that animal research is horribly cruel. Despite what the research community claims, federal regulations are extremely weak and poorly enforced, and some species — mice, for example — are completely excluded from any protection. Many investigations have shown just how bad conditions are.
This is about as far from anything resembling the “truth” as I’ve ever seen. Although fellow SBer Janet briefly fell for this lie, DrugMonkey set her straight in excruciating detail how it is not true that mice are excluded from protection from cruelty. Since DrugMonkey listed in excruciating detail the various animal regulations and how the fact that one law excludes mice and rats bread for research from certain protections does not mean that research mice are excluded from protection under certain mechanisms by the Helms Amendment, I won’t rehash the details. Suffice it to say that the laws and regulations covering animal research are many and overlapping–even for mice. What I’ll do instead is point out the view at the single investigator level
I happen to have five mouse protocols for various cancer and angiogenesis research project. For each protocol, the application was 13 pages long. Required were detailed experimental protocols, exact doses of any medications given, and detailed descriptions of how pain would be minimized or eliminated. Also required were literature searches showing that the research was not duplicative, along with a justification (with references) why no non-animal alternative could answer the same research question. Our institution has a highly helpful mechanism by which a veterinarian reviews all animal protocols before they are considered by our university’s Institutional Animal Care and Use Committee (IACUC) in order to catch problems or questions that IACUC would be likely to bring up. The vet found some, and I made some changes. Even so, it took another round of questions from IACUC and revisions to my protocols to get them approved. I estimate that I spent several hours on each one. Now that my protocols have been approved, we have veterinarians observing my lab personnel as they do procedures, monitoring the health of the mice, and calling us if they think any of them need to be euthanized. Moreover, we have to do exactly what we say in the protocol. If we deviate from our protocol without first getting an amendment describing the desired changes through the committee, we get in trouble.
So, it’s just not true that mice are not protected, and it’s also not true that federal regulations are weak and poorly enforced. Our school will get dinged by AAALAC and the feds if we do not adhere to strict regulations governing animal research.
However, that was just the appetizer. Here’s the main course:
But as someone who recently signed up for hospice, I have another major problem with animal research. I wonder if science would have found a cure for my leukemia by now if they weren’t sidetracked by misleading animal tests. I wonder if the chemo that I took for breast cancer would have been safer it hadn’t been tested in species that are so unlike our own.
The truth is that using animals to develop and test drugs is a system that doesn’t work very well. It’s an old paradigm, one that is fortunately beginning to change, however slowly. A growing number of scientists are developing some exciting (and more effective) non-animal alternatives. These changes have been inspired partly by concern over animal cruelty but also because animal research and testing have so often failed us. Some government agencies are even starting to call for more alternatives.
More than 90 percent of all new drugs which proved effective in animals end up not working for humans. It’s because animals — however similar they are to us — have different physiological systems. What works in a mouse usually doesn’t work in a human.
History is filled with stories of drugs that didn’t work in animals — Aspirin, for example — that ended up working in humans. And the obituary pages are filled with stories of people who died from drugs that looked safe in animals. The painkiller Vioxx, for example, tested safe in mice and five other species but ended up killing many thousands of Americans.
Ms. Chaitowitz’s story is very sad. I do not know the presentation of her breast cancer; so I do not know how much additional benefit she would have derived from her chemotherapy in terms of increasing her odds of survival, had she not suffered her complication; it could vary from a few percent absolute benefit to much more. However, in general, the benefits of chemotherapy outweigh the risks, even in early stage breast cancer, where the benefits are relatively small on an absolute scale. Unfortunately, individual patients are not statistics. For example, when I counsel patients on the risk of a wound infection after surgery, I will often say something like, “The risk is around 2%, but if it happens to you it’s 100%, and you won’t be reassured that you are in a small minority of patients.” The same applies to Ms. Chaitowitz’s case, but even more dramatically. Myelodysplastic syndrome is a known, albeit uncommon, complication of chemotherapy and radiation (around 0.3-0.7% risk in most recent series) that any competent medical oncologist would have informed her of, along with all the other risks as part of informed consent. Moreover, Chaitowitz in essence admits that the bone marrow transplant that she underwent gave her an additional two years of life. How were bone marrow transplants developed? In animals.
It is a frequent canard of the animal rights activist fringe that testing drugs in animals is only poorly predictive of how drugs will perform in humans. It is indeed true that there are inter-species variations in how drugs work. Indeed, one example discussed at the SSO Meeting (where I am now) was tumor necrosis factor-Î± (TNF-Î±). When human TNF-Î± was tested in mice, tumors shrank and tumor cells died with few side effects. In humans, however, TNF-Î±, although it can also shrink tumors, is so toxic that it’s impossible to achieve tumor-killing concentrations in the blood stream without life-threatening toxicity. However, when mouse TNF-Î± is used in mice, the same toxicities as seen in humans are observed. The difference was in how human TNF-Î± does not bind to one of the mouse receptors that mediates the toxicity.
In any case, I’ve written about these sorts of bogus arguments very extensively before; so I’ll only give you the CliffsNotes version here. Many are the features of tumor biology that have been discovered through animal research that could not possibly have been discovered through modeling. One example that comes to mind is tumor angiogenesis, the area to which my scientific hero, the late, great Judah Folkman, made the greatest contribution. Basically, tumors secret factors that lead to the ingrowth of new blood vessels ( a process called angiogenesis) to feed their oxygen and nutrient requirements. Without angiogenesis, tumors do not grow beyond a ball of cells less than 1 mm in diameter, because that’s as far as oxygen and nutrients can diffuse adequately in an aqueous medium. Blocking angiogenesis is one strategy by which to treat tumors, and antiangiogenic drugs are now becoming standard of care.
Now, it is true that animal models are not as predictive as we would like them to be. However, the distortion and misinformation comes in when animal rights activists make grandiose claims for various other non-animal methods. For example, if animal models don’t do as well as we would like, the alternatives that they propose either do much worse or are completely unvalidated. For example, cell culture models are in general even less predictive of drug activity than animal models. The NCI maintains a bank of tumor cells against which they test various compounds, and if animal rights activists think animal testing is inefficient, they should check out how few of the drugs that pass the first screen (which is all these cell lines are, a screening test) and go on to be used in humans. As for computer models, someday they may indeed decrease the need to use animal models, which, contrary to the animal rights portrayal of scientists as close-minded and cruel animal torturers, virtually all scientists would love to move away from. After all, most of us don’t like doing things that may hurt animals, even mice, and using animals is very expensive and onerous from a regulatory standpoint. Here’s the problem. Computer models are only as good as the assumptions underlying their algorithms and the data used to construct them, and we simply do not understand human physiology at a detailed enough level to obviate the use of animal models. If animal rights activists think that we do, I invite them to be the first to test new drugs on themselves that have only been tested in “computer models” or “microdosing” (which she mentions later), the latter of which is really useful only for excluding candidate drugs that are unlikely to do what they are predicted to do based on their pharmacokinetics from further development. To the extent that such techniques reduce the use of animals, that is all to the good, but animal rights activists don’t realize that such techniques complement, rather than replace, animal testing. It’s designed to reduce the number of drugs that go through animal toxicology testing.
Finally, Chaitowitz blames the system, rather than her disease:
If the chemo drugs I’m trying now don’t work, I do have one last option. I could try a Phase One trial. That’s when a drug looks promising in animals and is first tested in humans. My doctor started to tell me why so many participants die in Phase One trials — but it turned out I already knew the answer. Drugs that work in animals, he explained, usually don’t work in humans.
Wrong. Clearly Ms. Chaitowitz doesn’t understand the very purpose of a phase I trial. Phase I trials are not–I repeat, not–intended to test drug efficacy. What they are intended to do is to take a drug that looks promising based on preclinical studies in cell culture and animals and test it for the first time in a small number of human subjects, but not to determine if it “works” in humans, but rather to determine toxicities in humans, in essence identifying the maximal tolerated dose (MTD) and exactly what the dose-limiting toxicities are. This is done by what’s called dose escalation, where different patients get different doses, and the side effects and toxicities are tabulated. There is no expectation that the people participating in phase I trials will receive a benefit, although sometimes–uncommonly–they do. You will never see patients with a treatable cancer referred for a phase I trial, because to do so would be unethical, for instance. For cancer drugs, because patients with advanced cancer often have derangements in physiology that change the toxicity profile of drugs, drugs are usually tested in those patients. Occasionally, tumor shrinkage is observed, but because the number of patients are small, response rates can usually only be calculated after phase II trials. In any case, Ms. Chaitowitz, if she has not deteriorated too much, should participate in a phase I trial. It is the ultimate in using humans to test drugs. Of course, she probably wouldn’t like the fact that the dosage ranges to be tested in phase I trials are generally derived from animal data (although microdosing is being used more to estimate such doses). However, in Ms. Chaitwitz’s desired world, humans would face the risks of phase I tests without even the imperfect guideposts that prior animal studies have provided.
I’m sorry that Ms. Chaitowitz is dying. If she happens to see this, she probably won’t believe it. However, having just lost my mother-in-law to breast cancer, having watched a once vibrant woman wither away in a manner of months, I am more dedicated than ever to eliminating this scourge, and I would never wish such a fate on anyone, even J.B. Handley. However, if Ms. Chaitowitz thought to use the sympathy that her plight evokes to spread her nonsense about animal research, secure in the knowledge that few would be willing to criticize her because our sense of pity is such that we are loathe to criticize someone who is suffering, she’s got another thing coming. Chaitwitz should not be allowed to use her own impending death to falsely claim the role of a martyr to animal rights research, a martyr whose life would have been saved if it weren’t for those nasty, cruel, animal researchers who are too blind to accept her faith-based belief that animal research causes more harm than good and who also are, ironically enough, trying to find ways to save the lives of patients just like her.