A May 17, 2012 press release from Queen Mary, University of London was titled: “Zebrafish could hold the key to understanding psychiatric disorders.” Really? Zebrafish? Wow! All these years of studying humans and finding that very small genetic differences between monozygotic twins result in one twin suffering from schizophrenia while the other does not when all we really needed to do was study fish. The press release continues: “Study found fish can modify their behavior in response to varying situations.” OKaaaaaay. But what does that have to do with catecholamine levels and wiring in the human brain? Dr Caroline Brennan, from Queen Mary’s School of Biological and Chemical Sciences who led the study, is quoted as saying: “Zebrafish are becoming one of the most useful animal models for studying the developmental genetic mechanisms underlying many psychiatric disorders; they breed prolifically and we have many new and exciting techniques that allow us to explore their genetic make-up in the laboratory.” Hmmm.
Note that the above does not address the fact that different genes can accomplish the same function in different species, that the same gene can accomplish different functions in different species, and that fish and humans are differently complex, evolved systems among a host of other factors. Brennan continues stating: “Problems with behavioural flexibility, and general deficits in attention, are key symptoms displayed by people suffering a variety of psychological disorders related to impulse control, such as drug addiction, attention-deficit hyperactivity disorder (ADHD) and some personality disorders.” Ohhhhh! So the fish are going to help us treat ADHD, a disease that is not well understood in humans, that probably represents a variety of neuropathological states, and that probably has a strong environmental component? And fish researchers are going to accomplish this based in the fact that fish have been observed to change behavior.
The above would be laughable were it not tragic. Fish and humans also share numerous other traits and characteristics. We are both composed of the same 20 or so elements. We both have the same fundamental particles. And we both engage in respiration and elimination. Gosh! We must be fish. That’s silly isn’t it? But its the same reasoning, that superficial similarities are all that matters in terms of human disease and drug response, that the fish researchers are using. Make no mistake, humans and fish have things in common! But these commonalties are immaterial in terms of predicting the pathophysiology of human disease and drug response. Human disease and drug response vary immensely among humans and yet researchers expect a different species to inform about very specific pathology at the genetic and molecular level. This line of reasoning ignores evolution as well as complexity science.
Contrast the above claims by Brennan etc al with the following from Science, also published on May 17. Genetic variants are classified as rare if they are present in less than five people per thousand. These variations are also thought to be more important in contributing to disease than more common variations. Very thorough humans genetic studies have revealed that these rare variations are present in a lot of humans. Hayden, writing in Nature: “In a project sponsored by the US National Heart, Lung and Blood Institute in Bethesda, Maryland, researchers led by Joshua Akey and Michael Bamshad at the University of Washington in Seattle sequenced 15,585 genes in 2,440 people, and found that 86% of the variants discovered in the subjects were rare. More than 95% of the variants that were predicted to have a medical or biological consequence were rare variants.” (See (Nelson et al. 2012; Tennessen et al. 2012; Keinan and Clark 2012))
Hayden continues: “This widespread rare variation means that it will be very complicated to follow through on the promise of initiatives such as the Human Genome Project: to find the genes that, when mutated, cause human disease, and to predict disease risk for an individual on the basis of his or her unique genetic profile. Akey and Bamshad, for instance, estimated that each person in their study carried between 25 and 31 genetic variants that were shared by no one else in the study. Predicting the effects of these rare variants will not be easy.”
The papers suggest that scientists will need to study 20,000 humans in order to find enough variants to link to human disease. The vivisection activists will respond to the above by saying that we should just give up and study mice. Granted, studying mice would be easier. But it won’t predict human response to drugs and disease. For that we must study humans. I suggest we take the $20-50 billion being spent annually on animal models and start studying humans. This is the only way we will ever see personalized medicine.
Keinan, A., and A. G. Clark. 2012. Recent explosive human population growth has resulted in an excess of rare genetic variants. Science 336 (6082):740-3.
Nelson, M. R., D. Wegmann, M. G. Ehm, D. Kessner, P. St Jean, C. Verzilli, J. Shen, Z. Tang, S. A. Bacanu, D. Fraser, L. Warren, J. Aponte, M. Zawistowski, X. Liu, H. Zhang, Y. Zhang, J. Li, Y. Li, L. Li, P. Woollard, S. Topp, M. D. Hall, K. Nangle, J. Wang, G. Abecasis, L. R. Cardon, S. Zollner, J. C. Whittaker, S. L. Chissoe, J. Novembre, and V. Mooser. 2012. An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People. Science.10.1126/science.1217876. http://www.ncbi.nlm.nih.gov/pubmed/22604722.
Tennessen, J. A., A. W. Bigham, T. D. O’Connor, W. Fu, E. E. Kenny, S. Gravel, S. McGee, R. Do, X. Liu, G. Jun, H. M. Kang, D. Jordan, S. M. Leal, S. Gabriel, M. J. Rieder, G. Abecasis, D. Altshuler, D. A. Nickerson, E. Boerwinkle, S. Sunyaev, C. D. Bustamante, M. J. Bamshad, and J. M. Akey. 2012. Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes. Science.10.1126/science.1219240. http://www.ncbi.nlm.nih.gov/pubmed/22604720.