This is essay number three in a five part series examining the position that experiments on animals are necessary for life-saving breakthroughs; that without vivisection humans would die.
One constant theme in the previous essays, although perhaps understated by me, is that there are no other options when it comes to using animal in research. This is part of what is called the intact systems argument (ISA) (LaFollette and Shanks 1996) and basically says that in order to understand and or predict what a drug or disease will do in humans, scientists must study the drug or disease in an intact living system (read: dog or rodent or monkey or some other animal) because in vitro research and computer-based research cannot fully replicate a human system.
The beauty of this argument, like most lies, is that it presents a partial truth: in vitro and in silico research currently cannot predict human response with 100% accuracy. Sadly for the vivisection activist, the intact systems argument is an example, not only of bad science, but also of several fallacies including the fallacy of equivocation, that we saw in an earlier essay, and the perfect solution fallacy. First the science.
As I have said many times, empirical evidence contradicts the position that animal models can predict human response to drugs and disease and current knowledge from evolution and complexity allows us to put the empirical evidence in context (provides a theory or framework). (See Animal Models in Light of Evolutionfor more.) The reason the ISA is appealing is that it makes sense that in order to really understand and or predict what will happen in a living complex system (us) we need to study another living complex system, not chemicals in test tubes. Test tubes don’t have kidneys. This is intuitive and somewhat correct. The problem lies in the fact that your living intact system—your body—is different from my living intact system—my body. Currently, the only intact system that will predict with a very high reliability (a high positive predictive value (PPV) and negative predictive value (NPV)) what a drug or disease will do in you is you. Animal models, while intact systems, are in reality differently intact or, to put it more scientifically, differently complex. Therefore, what happens in a mouse does not predict what will happen in you. The ISA assumes that animal models do predict human response (have a high PPV and NPV) and therefore the ISA fails under even minimal scientific scrutiny.
Neither does it stand up to logical examination.
The perfect solution fallacy states that a solution is not acceptable because it is not perfect. In vitro and in silico tests, as of this writing, are not perfect so the vivisection activist wants to throw them out and use animals. This is obviously not a helpful attitude as the real question is the same for in vitro and in silico tests as it is for animal tests: “Does this testing method have a high enough PPV and NPV to allow scientists to use it as a predictive test or research method?” If a test does not meet this standard, be it an animal-based test or an in silico test, then the test fails the test of prediction. So, the perfect solution fallacy can be used against almost any biomedical test since a vast majority are not 100% predictive (have a PPV and NPV of 1.0) but do have a high enough PPV and NPV to justify their use as a predictive test. The reason the perfect solution fallacy is a fallacy is that a test does not have to be 100% perfect to be predictive.
However, the test does still have to meet a certain standard (have a high PPV and NPV, say in the neighborhood of 0.9) to be considered predictive. Currently, animal tests fail to meet this standard as do many in vitro and in silico tests. That is why so many drugs fail late in human clinical trials. (Tom Patterson, chief scientific officer at Entelos, likens the current practice of drug testing in humans during clinical trials to making airplanes, trying to fly them, and marketing the one that does not crash. (Hodgson 2001)) The pharmaceutical industry really has no idea what these drugs will do until they test them on a lot of people, or more realistically—release them to the general population. But while the animal model fails as a whole, there are in vitro and in silico tests that pass the prediction standard and industry is working on developing more. (It is in their best financial interest to develop predictive technologies as soon as possible.)
Moreover, the future of drug testing appears to be an in vitro and in silico-based testing future in the form of gene-based testing. Animal models are not working, despite genetic modifications, and based on what we know about complex systems, I do not think it is even possible that animal models will ever be able to predict human response. Even other humans fail at this and considering animals and humans are examples of complex systems, we will never be able to make a mouse that resembles a human more than another human does.
The reason the ISA is an example of the fallacy of equivocation is because the vivisection activist equivocates on what the standard is. When discussing animal tests, a low PPV and NPV are acceptable but when analyzing in vitro and in silico testing he demands a high NPV and PPV. This is one of the problems / examples of disingenuousness of the so-called alternatives movement, exemplified and supported by organizations like FRAME, CAAT and the HSUS. The standards for replacing an animal test with an in vitro or in silico one are variable. Sometimes the committee requires a better test but at other times it requires one that is equal to the animal test in terms of PPV and NPV even if the animal test has a really low PPV and NPV. This is the logic that comes from the alternatives community. We have tests that are better than some of the animal tests but we will not be allowed to use them until we come up with a replacement to the animal test that is just as bad as the animal test. This is lunacy but sadly is also true.
I (and the pharmaceutical industry and reality) have one standard and it is quantifiable. Unfortunately, most tests currently available to the pharmaceutical industry do not meet that standard. The problem is not that in vitro tests are bad an animal tests are good. The problem is that there are not enough predictive tests of any variety. But the predictive tests that do exist for drug development (for example for ADMET) certainly seem to be in the form of in vitro and in silico and the ones on the horizon also seem be non-animal. (See the Elferink article mentioned in my blog It’s A Mindset Thing.)
There is another aspect to the no other options argument beside the ISA.
There are procedures that are performed on animals that cannot be performed on humans, brain mapping in monkeys for example. The vivisection activist attempts to justify these experiments by pointing this out. But the assumption that underlies the position is untenable. Namely, that these experiments will be predictive for humans. This gets us back to the ISA and the prediction problem. So while the vivisection activist is correct in saying that these experiments cannot be performed in humans—thus implying that we either do them in monkeys or in your child or lose the life-saving knowledge—he is wrong in equating progress in science, which brain mapping studies certainly are, with advances that will lead to cures for humans. The two are not synonymous. At times, advances in science have lead to spectacular advances in medical care but this is actually the exception not the rule (see Is the use of sentient animals in basic research justifiable?).
Similarly, vivisection activists will point to other experiments that are performed on animals or with tissues from animals. The question in all these cases is the same: “If the experiment relies on animals or animal products, is the outcome advancing medical care or merely science in general?” If the animal experimenter wants to argue for the use of animals to advance science in general, she is free to do so. Society can decide the issue. However, it is disingenuous, and routine, when she seeks to justify her experiments in terms of advances in medical care while in reality she is doing basic science research and hence advancing science in general.
One final thought on the no other options argument. Vivisection activists like to demand a one-to-one replacement for their particular form of research. If their opponent cannot produce a one-to-one replacement, they then claim victory in the argument. For example, as I stated earlier, certain brain-mapping studies are performed in animals and such research would be considered unethical to do in humans. Since the vivisection activist has produced an example of such an experiment, she then says that these experiments must continue since there are no alternatives. (The LD50 toxicity test is another example. We cannot give large doses of new drugs to humans until 50% of them die.) As we have seen, this position begs the question of relevance for humans and advancing medical care but there is also another problem arising from this. The real question is not: “Is there a one-to-one replacement for something that is not predictive in the first place?” That question itself is trivial. Rather, the question should be: “Are there medical research options that do give us knowledge about humans and why are we not funding them?” The answer is a resounding yes to the first part and I will address the second part in another blog. Human-based research gives us knowledge about humans every time (provided it is properly performed). There does not have to be a one-to-one replacement for the LD50 or brain mapping in monkeys. The goal is not to find replacements so vivisectors can transition from animal to nonanimals. That is white coat welfare. The goal is to cure human disease and ease human suffering and society should fund whatever research does that best. Scientists are smart people, if the uneducated guy that loses his job can find employment elsewhere, the scientist with a doctorate should certainly be able to do the same (probably in the same university and even in the same lab; not exactly a burdensome expectation). I am opposed to white coat welfare! Especially when it interferes with finding cures for cancer, Parkinson’s, AIDS, and other disease.
We can do brain mapping on monkeys and discover everything there is to discover about the brains of monkeys and still be no closer to curing neurological diseases in humans. This is in fact what has happened in cancer research and AIDS research. We know a lot about cancer in mice and SIV in monkeys but all this knowledge has produced little in the way of human treatments or cures. I have referenced in previous blogs, numerous scientists who say exactly the same thing.
The no other options argument is a lie in the form of a red herring.
Hodgson, J. 2001. ADMET--turning chemicals into drugs. Nat Biotechnol 19 (8):722-6.
LaFollette, Hugh, and Niall Shanks. 1996. Brute Science: Dilemmas of animal experimentation. London and New York: Routledge.