Part II: Approaching Thirty Years in Science: What Has Happened, and What Should Have Happened, in That Time
Jarrod Bailey, Ph.D. — CCS Director of Science & Technology
This is the second of a three-part blog, describing my journey through my scientific career, from the end of my days as a student, through to working with the Center for Contemporary Sciences.
Part II: Doing Something About My Frustrations Over Animal Research: Moving Away from the Bench and Out of the Laboratory
In the previous installment (Part I) of this three-part blog, I described my scientific epiphany as a post-doctoral research scientist. My dissatisfaction with how science was conducted, based largely on research using animals to model human biology, had grown to become irresistible. This frustration was not simply ethical. Scientifically, I was absolutely convinced that animals were such poor models for human biology, that I had to do something about it.
One lunchtime in the lab, the intensity of my epiphany urged me into action. Could I do something about this, as a scientist? Could I use the knowledge and experience gained in my 14 years of higher education and research, to help to change how biomedical science was conducted, for the better? Could I help reduce the misleading results and conclusions, to avoid the dead-ends, and to help to save animals in labs? And how?
One lunchtime, I sat at my office desk and wrote letters to more than 30 organizations that campaigned against animal research. I received some exciting responses, and began to work on a project in my spare time for one group. Soon, I was working full time for a UK-based organization campaigning for research modernization and for a safer and more effective drug development process. I became a consultant, working for several groups on this issue, on varied projects.
I have done this now for around 17 years. In this time, I have published dozens of scientific papers and book chapters on diverse topics, all addressing the human relevance of animal models in scientific research and product testing, and human-specific in vitro methods of investigation. Topics include:
· Statistical analyses showing that animal testing of new human drugs is poorly predictive of safety. There remains no robust published evidence to support current regulatory paradigm of animal testing in supporting safe entry of new drugs into clinical trials. In fact, my own studies, along with two salient subsequent reports, actually support the contention that tests on rodents, dogs and monkeys provide next to no evidential weight to the probability of there being a lack of human toxicity from new drugs, when there is no apparent toxicity in animal tests. It is essential that the pharmaceutical industry and its regulators seek a roadmap to embracing a comprehensive and integrated human-biology based strategy for this purpose as a matter of urgency.
· Numerous and widespread genetic differences are at the root of poor human relevance of monkey and chimpanzee experiments. Critical analyses of the relevance of monkey studies to human biology indicate that genetic similarity does not result in sufficient physiological similarity for nonhuman primates to constitute good models for research, and that nonhuman primate data do not translate well to progress in clinical practice for humans. Salient examples include the drug testing/development, HIV/AIDS, Alzheimer’s and Parkinson’s diseases and stroke. Key molecular differences underly these inter-species disparities, with significant differences in all aspects of gene expression and protein function. The use of nonhuman primates in research must be considered of questionable value, particularly given the breadth and potential of NAMs.
· Testing of substances in animals for potential harm to unborn children (developmental toxicity) are poorly predictive. Animal tests in this area do not provide reliable data that are predictive for human responses and, even if they did, the tests are too expensive and time-consuming for application to the very large number of substances that need to be tested. It is estimated there are already more than 100,000 man-made chemicals to which humans may be exposed on a regular basis, and it is therefore widely accepted that developmental toxicology tests using animals could not possibly be used to assess all new and existing chemical substances, due to the scale of its demand upon time and resources. It is therefore imperative that alternatives (such as those described here) are embraced, further developed, accepted and used — as a matter of urgency.
· Chimpanzee research — prevalent in the US until funding was withdrawn in 2011 — was poorly predictive for humans. Areas included HIV/AIDS, hepatitis C, cancer, and others. Over 85% of chimpanzee published research is either not cited, or cited only by studies that do not report human medical advances. Of the few citing papers that do report human medical advances, chimpanzee research is not a contributory factor. Greater than 85 HIV/AIDS vaccines have been developed, almost all of which were successfully tested in chimpanzees, yet in 200 human trials none provided human protection or improvement of symptoms (this has since been updated in a paper in press). Hepatitis C research with non-chimpanzee methods had increased 80-fold over two decades, while research involving chimpanzees declined by almost 70% to an historic low.
· The human relevance and promise of clinical benefit from animal ‘breakthroughs’ are greatly exaggerated in the press. Over-speculation and exaggeration of the human relevance of animal research is widespread in the UK national print media. Of 27 high-profile, unique published animal-based ‘breakthroughs’ promising imminent clinical benefit in 1995, only one had clearly resulted in human benefit, despite a time period of greater than twenty years to allow that research to come to fruition. Failures included therapies for cancers, HIV/AIDS, Alzheimer’s disease, multiple sclerosis, deafness, and organ transplantation.
· Substantial evidence warrants great concern over the poor efficiency and specificity of CRISPR-mediated genetic modification of animals, despite recent improvements. These issues cause persistent, adverse, ethical, and scientific consequences for GM animals, which may never be sufficiently resolvable.
· Stress experienced by animals in labs significantly affects scientific results, and there is little that can be done about it. Stress experienced by animals in labs is difficult to mitigate and can result in considerable psychological and physiological welfare problems. Physical consequences include adverse effects on immune function, inflammatory responses, metabolism, and disease susceptibility and progression. These effects must have consequences for the reliability of experimental data and their extrapolation to humans, in addition to causing welfare problems for the animals, and this may not be recognized sufficiently among those who use animals in experiments.
All in all, I, and many other authors over time, have published a considerable volume of such evidence. It is comprehensive, robust, powerful and makes a formidable case. Yet, the impact this evidence has had on changing how science is done, and on making it more human relevant and translate better to clinical success, has not been as great as it deserves. In the next, and final, installment of this blog series (Part III: “A Shift That Will Revolutionize Biomedical Science”), I outline how an increasing focus on what human-based research can do, rather than what other approaches cannot, could help expedite the urgently needed paradigm shift. I also describe how CCS came about, and what my colleagues and I are doing, and will do, to ensure that the change that science demands is realized.