In this essay, I will briefly explain Trans-Species Modeling Theory (TSMT), describe why the animal protection movement should embrace TSMT, and examine why the ignorance, naivety, and duplicity of some leaders in the animal protection movement prevent this from happening.

A common saying in science is that if you can’t explain your research to a small child, you don’t understand it yourself. While this is somewhat true, it is only true if the small child does not ask questions he or she is incapable of understanding. In other words, such explanations are only true on a very superficial level. Other positions or explanations appear straightforward until you read them and realize you don’t really understand all the words being used. TSMT is an example.

Trans-Species Modeling Theory (TSMT) states: “While trans-species extrapolation is possible when perturbations concern lower levels of organization or when studying morphology and function on the gross level, one evolved, complex system will not be of predictive value for another when the perturbation affects higher levels of organization” [1].

The above description of TSMT is 100% true and if the reader has adequate understanding of evolutionary biology, evo devo, complex systems, critical thinking, the empirical evidence concerning animal models, and how medicine is practiced, the above is all the reader really needs to know. It is a concise and accurate little explanation. For most people however, more knowledge in needed in all of the previously mentioned subjects before they approach TSMT and then they need to integrate all that knowledge in order to understand TSMT. This situation is not unique. Transdisciplinary research is gaining popularity and along with that popularity has come difficulty for some in comprehending it. See references [2- 9].

But why is TSMT so important to the animal protection movement and why is it the anti-thesis of the Three Rs mentality? TSMT is the only science-based position that is a theory, meaning it is a “comprehensive explanation of some aspect of nature that is supported by a vast body of evidence” and as such can be used to make predictions about future events. TSMT explains why animal models did not, currently do not, and never will have predictive value for humans when perturbations occur at, or influence, higher levels of organization: for example when studying drugs and disease. Dramatically modifying a mouse’s genome with CRISPR will not change its predictive value nor will creating chimeras. The initial conditions of the complex systems will always differ sufficiently to result in inadequate predictive values. TSMT ends vivisection just as Einstein ended talk of faster than light travel and the laws of thermodynamics ended all hope for machine that produces more energy than it uses.

Currently the animal protection movement in general and the scientists and scientist wannabes in the Three Rs movement act like they have no idea what TSMT is. There are many possible reasons for this but in reality they boil down to three: ignorance, naiveté, or an agenda. This is why I discussed these topics in parts I-III. In terms of those with an agenda, if the science to wipe out your industry, along with your job, exists, you had better ignore it as long as you can and hope everyone else does too. Downplay it, belittle it, tell everyone that you and others have proven it false, do whatever it takes to make sure no one takes it seriously. That will take care of the naïve people. As the science behind TSMT is hard, the ignorant will be reluctant to expend the effort required to understand it. Hence, those with an agenda will win.

The scientists who work for the Three Rs community are the lowest of the low. If they had a little more going for them they would be politicians who would sell their children for a few more years in office. But given their other inadequacies, selling out 1) science, 2) current and future patients, and 3) animals for moderate gain is all they can currently accomplish. Sadly, many people in the animal protection community listen to them and take them at their word. These are the naïve animal protectionists I discussed previously. Because they lack critical thinking skills they have no mechanism for judging claims or character and are easily taken advantage of, frequently in many diverse areas.

I have explained TSMT and all of its components and listed references where one can learn more about complex systems, evo devo, and everything else required for understanding TSMT. (See Resources section.) It is not incumbent upon me to explain TSMT so a small child will understand it while simultaneously using the same explanation to defend it to the scientific community. Such would be nonsense but that is what some have suggested.

If a person cannot explain to me what TSMT is, or explain it in a journal article to my satisfaction, then that person does not understand it and his or her comments on it are meaningless. I have published articles in peer-reviewed journals explaining it and the referees found the essays consistent with current science and understandable. TSMT essentially ends vivisection. Nothing more is needed. At least nothing more from science. The superficial differences between humans and some animal model of human disease are immaterial in light of TSMT. TSMT is the only explanation for why all animal models will always fail—currently animal modelers acknowledge failures but claim that future versions of these models will succeed. Pointing out past and current failures of specific animal models e.g., primates, does not address this counter argument. Moreover such articles are superfluous in light of TSMT.

More is needed from so-called advocates for animals. Every time someone in the animal protection community publishes yet another article

• about the superficial differences between humans and some animal model of human disease being studied
• about a new replacement or why one or more of the Three Rs is needed for animal model X
• about why we need to study a specific animal model more and evaluate its effectiveness with systematic reviews
• about why we need to study a specific animal model more and evaluate its effectiveness with direct comparisons using human data
• about the futility of using a particular animal model for research or testing

he or she

• reveals his or her own lack of knowledge (ignorance), naivety, or agenda
• undermines the validity of TSMT by ignoring it and therefore
• sets back the end of vivisection by a few more years.  

Ego and self-aggrandizement have no place in the science of vivisection debate. If the usual authors who write these things love animals, then they should stop writing and lecturing. You do not know what you are doing and you are diverting attention away from the only thing that will end animal modeling! I doubt you have the capacity to understand TSMT and even if you do, learning everything you need to know will require several years. I don’t see the usual authors taking that much time out of their “selfless work for the animals” to actually become competent.

Examples of the animal protection movement and or Three Rs scientists being duplicitous or apparently misunderstanding science include the following. Robert Coleman stated in 2015 [11]: “Until we know the true predictive value of animal-based methods for predicting clinical safety issues, it is impossible to assess the advantage or otherwise of non-animal based approaches.” In reality, there have been numerous studies assessing this issue and they revealed that animal studies had no predictive value for humans. Coleman knows this.

Coleman continues: “Supporters of the continued use of animals argue that, while they do not provide an absolute indication of either efficacy or safety, in the absence of any other approach, one that is somewhat unreliable is better than none at all. Such an argument has some merit, if indeed it is valid.” Based on that logic physicians should still be employing blood-letting because there are conditions where lowering the red blood cell count is indicated. The problem is these conditions are rare and as a treatment for most conditions, blood-letting would do far more harm than good. Likewise, we have no predictive animal models even though the outcomes from animals do occasionally overlap with the outcomes from humans just as blood-letting can occasionally be successfully used to treat a patient. Science is about expressing your knowledge in numbers. “Somewhat unreliable” is meaningless. Predictive values actually measure, and express numerically, how predictive a modality is. Predictive values are so low for animal models that, for applications like drug testing and disease research, they cannot be used as human surrogates in any meaningful way.

Coleman continues:

Secondly, it is important to understand that we really don’t know how good existing animal-based methods are. In the field of efficacy, there is a wealth of evidence that results obtained by using experimental animals can be hugely misleading.

The second part contradicts Coleman’s initial statement that we really don’t know how good animal models are. Given the theory of evolution, proving animal models have no predictive value in efficacy has implications for safety and disease research in general. TSMT shows the reason for failures in safety and efficacy and everything else is because of different initial conditions in complex evolved systems. This is what the empirical evidence has been revealing for decades.

Coleman continues:

Here, we have the advantage that drugs that promise efficacy in patients on the basis of animal data can advance into clinical testing, and their utility can be directly assessed. For the majority of these drugs, the clinical outcome has been disappointing. With safety, the issue is different, as drugs with identified safety issues in animals will seldom, if ever, advance to clinical testing, thus the relevance of the animal data to safety in humans may never be determined.

The statement regarding safety is false. There are numerous drugs that were tested retrospectively on animals or where the animal tests were re-evaluated after the results in humans were known. Some of these studies were large enough to give us reliable predictive value calculations hence we are well aware of the predictive value of safety studies in animals. Coleman also knows this.

Coleman continues:

However, what we do know is that many drugs identified as safe in pre-clinical profiling eventually prove to cause serious and use-limiting side effects in human subjects. The key question is, “Could such failures have been avoided, had we relied on human-based test methods?” Until we know how frequently non-animal methods could have identified safety issues that were missed by animal tests, it is impossible to assess the advantage or otherwise of those methods.

This statement is absurd. Coleman is essentially saying that since we do not know how often human-based tests, some of which are still in development, get the right answer we should continue to use Ouija boards to predict human responses. I don’t care how good or bad the human-based tests are, we should never use Ouija boards to predict anything because we know Ouija boards have no predictive value. Ask enough questions, phrased correctly and the Ouija board will, through sheer random chance, give a correct answer occasionally. This will give it a very low predictive value and thus, other than being used to scare teenagers on camping trips, is useless.

Coleman continues:

It is a fact that, despite the continued use of animals as human surrogates in pharmaceutical research, there has never been a solid, published, peer-reviewed study demonstrating fitness for purpose, whereas reviews identifying the shortcomings are abundant.

Some people with a training in science might say that this gives us yet another reason to abandon them. The same judgment can be rendered about trephination and other long-abandoned treatments. So why all the talk about waiting for replacements before abandoning animal models? Trephination was used to treat patients who probably had schizophrenia. We still have no cure for schizophrenia, so why not use trephination? Because it doesn’t work.

Coleman continues: “It is for this reason that any information that sheds light on the actual value of animal-based testing for its intended purpose is of inestimable worth. Until recently, much evidence, while valuable, has been indirect.” Again, this is absurd. There is plenty of data both directly about safety testing and indirectly about other animal uses informing society about safety testing. I have discussed all of this and what it means for TSMT. If evolution is the reason trans-species extrapolation at higher levels of organization is impossible for efficacy then it is also going to be why safety testing and target identification and disease mechanisms are going to be unreliable in animal models. There is only one evolution. Coleman cannot get it to say two different things. Animals models of currently undiscovered disease Q will not have predictive value either.

I address the remainder of Coleman’s article in “The ethical implications for humans in light of the poor predictive value of animal models” published in the International Journal of Clinical Medicine (Special Issue on Medical Ethics) 2014:5; 966-1005. In that article I also address similar nonsense by Bailey J, Thew M and Balls M in their paper: “An analysis of the use of dogs in predicting human toxicology and drug safety” published in ATLA 2013:41; 335-350. But there is overlap with Coleman’s essay. Unsurprisingly, a large number of articles reinforcing the status quo appear in ATLA.

Given Coleman’s excellent background in science, one must ask why he would state such nonsense. Coleman is not ignorant and he is not naïve. Ditto for Balls, M. I think that realistically only leaves one answer to the question.

One reason it appears that the scientific community is not commenting more on TSMT is that the usual Three Rs people or the ignorant or naïve in other animal protection organizations are being asked to write the “state of the art” articles that raise questions about animal modeling [11]. These people either have an agenda or do not have the requisite knowledge. (See the Dunning-Kruger effect and previous essays for why this is so.) When a naïve or ignorant animal protectionist writes such an article they either say essentially all the same things the Three Rs people say or write something equally irrelevant to the debate. No progress is made in terms of ending vivisection based on the very bad science that it is.

I was young once and thought all the answers were either known to me or at my disposal. After college I questioned that position and after medical school I saw it for the folly that it was. But most people do not have the education that I was fortunate enough to obtain and hence most still suffer from delusions of grandeur and easily fall into the Dunning-Kruger effect. I doubt such people will read these four essays much less learn anything from them. Those with an agenda don’t care. And vivisection will continue.

Related essays

Working with animal protectionists.

What is needed in order to end vivisection?

How animal protection groups are delaying the end of vivisection.

References

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2. Russell W. Forging new paths—transdisciplinarity in universities. 2000. www.wisenet-australia.org/issue53/transdis.htm
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4. Committee on Facilitating Interdisciplinary Research, National Academy of Sciences, National Academy of Engineering, Institute of Medicine . Facilitating interdisciplinary research. The National Academies Press; Washington DC: 2005. www.nap.edu/catalog.php?record_id=11153#toc
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7. Sommerville MA, Rapport DJ, editors. Transdisciplinarity: recreating integrated knowledge. McGill-Queens University Press; Montreal QC, Canada: 2002.
8. McMichael AJ. What makes transdisciplinarity succeed or fail? First Report. In: Somerville MA, Rapport DJ, editors. Transdisciplinarity: recreating integrated knowledge. EOLSS Publishers Ltd.; Oxford, UK: 2000.
9. The International Center for Transdisciplinary Research (CIRET) Convento da Arrábida Charter of transdisciplinarity. Adopted at the First World Congress of Trandisciplinarity. 1994. Portugal. nicol.club.fr/ciret/english/charten.htm
10. Coleman RA (2015) Likelihood ratios in assessing the safety of new medicines. Altern Lab Anim 43: P2-4. http://www.ncbi.nlm.nih.gov/pubmed/25803000
11. Greek R (2014) Letter to the editor. Theoretical Medicine and Bioethics 35: 389-394. http://link.springer.com/article/10.1007/s11017-014-9305-5?sa_campaign=email/event/articleAuthor/onlineFirst Pre-print available at http://www.afma-curedisease.org/tbme.aspx