Many species many responses to drugs and diseases
Friday October 28, 2016
Written evidence was presented in the UK Parliament in May 2016 by The Humanimal Trust, an organization supporting the concept of One Medicine: “There is significant, wide-ranging evidence that confirms most diseases on earth affect both animals and humans and that we share an overlapping collection of biological characteristics and genetic profiles.” The notion that science can learn how disease and drugs will affect one species by studying another is an attempt to repackage old, outdated science in modern language. The notion is called One Health, “Many Species. One Medicine.™—The concept of one single medicine for all species,” as well as similar names. I published an article that can be accessed online addressing this in 2012.
The Humanimal Trust appears to be the British version of this concept. I quote below from the written evidence presented.
The Humanimal Trust is the first UK charity set up to promote the advancement of animal and human healthcare through a One Medicine approach that integrates human and veterinary research. One Medicine embodies the view that both human and veterinary medicine share not only similar biological underpinnings but often also the same scientific and technological challenges. We believe that it makes clear clinical and economic sense that advances in human and veterinary medicine should be made in tandem to the advantage of both humans and animals .
This is exactly the premise of animal modeling and has been since before Claude Bernard. The science supporting this has always been wrong but was somewhat excusable prior to the 20th century. Now, both empirical evidence as well as theoretical concerns exist to disprove the notion. However, even if sufficient science exists to prove a concept wrong that is important to you because that concept pays your salary, or most of your ego is wrapped around it, then you will probably continue to accept and promote it. And that is what is happening with The Humanimal Trust.
The written evidence is the usual promises of what diseases will be cured if the One Medicine concept is well funded. The written evidence goes on to state:
The rationale for studying natural (or ‘spontaneous’) diseases and disorders in animals is to develop a translational bridge between preclinical data derived from normal laboratory animals and clinical trials in human patients.
This is exactly what has been attempted for decades in normal animal modeling and it has resulted in a 90% failure rate in terms of bringing new drugs to patients. This has obviously failed patients and society but has also increased the cost of new drugs that do make it to the market
Veterinary clinical trials cannot replace carefully controlled clinical trials in humans, since efficacy in a human disease setting can only be determined from clinical studies in patients with the disease.
And this is one of the big reasons clinical trials fail—the animal studies cannot predict the outcomes for the two areas they are used: efficacy and safety. This reality undermines the entire One Health concept and The Humanimal Trust. The purpose of studying animals is not to find neat little commonalities or differences but to find new treatments for humans. It has been well established that animal models offer no predictive value on this. Claiming they do is simple malfeasance.
However, evaluation of candidate therapies in veterinary clinical patients makes sense from ethical, scientific and financial perspectives . The use of naturally occurring disease eliminates the need to use purpose-bred research animals, and is therefore in line with the concept of “reduction” that is espoused in Russell and Burch’s 3Rs .
No it doesn’t. The concept is scientifically untenable and hence will not accomplish anything regardless of whether is it implemented in a vivisection lab or pet hospital.
Veterinary clinical trials can be extremely effective in confirming the suitability of novel routes of treatment delivery and the effectiveness of dosing. They are also extremely valuable in confirming the selectivity and the safety of the proposed treatment, making it possible to identify and mitigate potential unwanted, “off-target” effects. As stated in a recent review on the use of stem cells in veterinary clinical trials :
The above contradicts the previous caveat about human trials being needed to establish efficacy. But it is also demonstrably wrong. Hurko and Ryan of Wyeth 2005:
In the pharmaceutical industry, translational research refers specifically to those activities conducted to bridge the gap between drug discovery in animals and drug development in human patients . . . In recent years, only 9% of compounds that entered phase 1 survived to launch. Over 50% of this attrition resulted from failure to demonstrate efficacy in phase 2 studies, a 15% increase in phase 2 failures over the last decade. Compounds that worked beautifully on cloned human proteins and in animal models more often than not proved ineffective in human disease. (Hurko and Ryan 2005)
Arrowsmith in 2011:
The Centre for Medicines Research International has noted that the average for the combined success rate at Phase III and submission has fallen to ~50% in recent years . . . Almost 90% of the failures across all therapeutic areas were attributable to either lack of efficacy (66%) or safety issues (21%). (Arrowsmith 2011)
Veterinary clinical trials are also extremely useless “in confirming the selectivity and the safety of the proposed treatment.”
'It follows that companion animal research offers a preclinical window into the feasibility, safety, and effectiveness of therapies in the context of a naturally complex, if not hostile environment that more accurately reflects the human condition.
No, just the opposite is true.
Approximately 90% of all new medications that were shown safe and effective in animals were toxic or ineffective in humans. This is a terrible track record and this alone proves animal models fail at what they are supposed to do. Further, animals do not keep bad drugs off the market but rather allow drugs to be selected for development in what amounts to a random fashion. When new medications are developed in a random fashion some will help humans but most will not and the ones that do not help usually actively harm humans. The net effect of animal-based research and testing is very negative for patients. This is really all one needs to know about using animals as human surrogates to study disease or develop drugs.
The rest of the submission continues to deny that humans and animals are examples of evolved complex systems that are differently complex and touts the impossibility that funding One Health research will cure diseases. Were the stakes not so high The Humanimal Trust should be praised for their unflinching audacity to present nonsense as science. For more on the science behind why one evolved complex system has no predictive value for another in terms of studying disease and drug development, see the articles in the resources section of the website.
It is impossible to fully counter all the misrepresentations, lies, and bad science represented by industry- and university-backed groups who appear to be competent and who invite us to trust them. The Humanimal trust is a slick marketing campaign as are many such pro-animal modeling schemes. The science on the other hand is difficult and accessible only to those with advances education is science in general and specific areas of science in particular. Even in the scientific community, these people are few and far between. Most scientists just go along with the status quo despite knowing nothing about it. This is not a flattering portrayal of the scientific community but it is true. At the end of the day, most of them just want to pay their mortgage.
This is why we have been asking the UK to support a proper scientific debate along the lines of the peer-reviewed system currently used in scientific journals. It is not reasonable to ask average people to decide matters understandable only to a relatively small percent of scientists. It is not reasonable to ask people to read my papers and come to their own conclusion when the pro-animal modelers are coming to opposite conclusions. A vast majority of people simply lack the expertise to make such a judgement. However, there are experts in these areas of science who are impartial on this subject and their voices should be heard.
We have been calling for a peer-reviewed debate for many years now. When one publishes in the scientific literature one’s peers, that is other scientists with expertise in the area you are writing about, review your work and decide whether it is consistent with what is known and whether your article should be published. We have called for those who oppose our position to prepare a position paper where they explain their position and answer the questions posed by my position. I will do the same and a dozen or so agreed upon experts will then read the papers and render a decision about who is right on the science. A short public debate summarizing the positions can be held at the end of process and the experts can announce their decision at that time.
If the science does not support animal experimentation, then there should not be an argument about the ethics of using animals in research and testing.
Arrowsmith, John. 2011. "Trial watch: Phase III and submission failures: 2008 - 2010." Nat Rev Drug Discov 10 (2):87-87. http://dx.doi.org/10.1038/nrd3375
Hurko, O., and J. L. Ryan. 2005. "Translational research in central nervous system drug discovery." NeuroRx 2 (4):671-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16489374