The last common ancestor shared by humans and pigs was approximately 79-97 million years ago. Mice and humans shared a common ancestor approximately 75 million years ago whereas humans and chimps diverged 5-7 million years ago. On an evolutionary scale, humans are about as related to pigs as we are to mice. Nevertheless, when the genome of the Wuzhishan pig was published in GigaScience (Fang et al. 2012), journalists, along with the researchers and universities involved, made some bombastic claims.
Fang et al claimed: “Understanding the pig counterparts of human drug targets is vital for pre-clinical drug screening, using pigs as a model organism.”
Alison Abbott writing in Nature states that scientists have been using pigs “to try to create more faithful models of human disease” and that the pig genome will speed this process, “and perhaps even allow pigs to be engineered to provide organs for transplant into human patients.”(Abbott 2012) Abbott continues:
The NIH launched the NSRRC in 2003 to encourage research in pig disease models. Pigs are more expensive to keep than rodents, and they reproduce more slowly. But the similarities between pig and human anatomy and physiology can trump the drawbacks. For example, their eyes are a similar size, with photoreceptors similarly distributed in the retina. So the pig became the first model for retinitis pigmentosa, a cause of blindness. And four years ago, researchers created a pig model of cystic fibrosis that, unlike mouse models, developed symptoms resembling those in humans.
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Noting similarities between species is meaningless in terms of how the animal reacts to drugs and disease. For example, the size of the eye says nothing about the wiring. Any animal can be a model for a disease. Nevertheless, this begs the question: “What kind of model?” If the model is said to be predictive for how humans respond to drugs and disease, the fact that animals and humans are evolved complex systems suggests the predictive value of the model will be minimal. Conversely, if the model is to be used as a heuristic, then it could have value. It probably will not be funded; but it could have heuristic value.
Apparently, pigs will become the new animal model of choice. Abbott:
Pig models are now being developed for other common conditions, including Alzheimer’s disease, cancer and muscular dystrophy. This work will be enriched by the discovery, reported in the genome paper, of 112 gene variants that might be involved in human diseases. Knowledge of the genome is also allowing scientists to try to engineer pigs that could be the source of organs, including heart and liver, for human patients. Pig organs are roughly the right size, and researchers hope to create transgenic pigs carrying genes that deceive the immune system of recipients into not rejecting the transplants.
Pigs and humans share many genes but this does not mean they are used in the same way or that modifier genes interact with the shared genes in the same way. The same genes can also be regulated and expressed differently. This alone invalidates the notion of “pig as a predictive model” for human response to drugs and disease.
A press release from GigaScience, echoes the above: “Researchers provide a whole-genome sequence and analysis of a miniature pig that serves as a model organism for human medical studies and therapeutic drug testing.” The press release from the University of Edinburg states: “Pig gene discovery could help combat animal and human disease.” The press release from BioMed Central states: “An in-depth analysis of this sequence, along with comparison to human genes, has provided a wealth of knowledge for use in medical engineering and drug design.” Clearly, such statements imply the pig model will be of predictive value. Rodents have failed as predictive models so the animal model community must offer the public another model, making the same promises they made about rodents. The “pig as human” is simply the latest iteration of this con.
In a related study, Groenen et al (2012) compared the pig (Sus scrofa) genome to the genomes of other mammals. The authors state:
The pig is an important biomedical model and the ability to generate transgenics and knockouts in combination with somatic nuclear cloning procedures has resulted in a number of models for specific human diseases. . . . We observed 112 positions where the porcine protein has the same amino acid that is implicated in a human disease . . . These porcine variants are of interest, as they will allow detailed characterization in an experimental model organism whose physiology is very similar to that of human.
There were moments of sanity in the announcements. The GigaScience press release stated:
However, the researchers also found that there were several situations where target genes showed important differences from the human versions. This information is of great use as well, as it provides a clear indication of the types of drug testing for which this organism is not as useful, saving unnecessary experimentation, time, and money.
There are far more differences between the genomes of humans and pigs than the genes described above. What all these statements have in common is the failure to place this scientific breakthrough in the context of complexity theory. Living organisms are complex system and this explains, in part, why very small differences in genetic make-up (initial conditions) can result in dramatic differences in response to perturbations such as drugs and disease. Even single nucleotide polymorphisms (SNPs) between humans can result in life-threatening disease.
There is one thing that sequencing the pig genome will be useful for: learning about pigs. Abbott:
Back on the farm, early knowledge about the pig genome led to the discovery in 1991 of a gene involved in porcine stress syndrome, in which the stress of overheating, being moved or even having sex causes the animals to die suddenly4. It then became possible to test for the gene and select pig stocks free of it.
Sequencing the pig genome is a scientific accomplishment and it will aid in the study of comparative physiology, genomics and evolution. But the pig will not be a predictive model for human response to drugs and disease. The fact that the scientists involved in sequencing the pig genome are oblivious to a large field of science (complex systems) is cause for concern.
Abbott, Allison. 2012. Pig geneticists go the whole hog. Nature, November 14, 2012 2012 [cited November 19 2012]. Available from http://www.nature.com/news/pig-geneticists-go-the-whole-hog-1.11801.
Fang, et al 2012. The sequence and analysis of a Chinese pig genome. GigaScience 1 (1):16.
Groenen, et al. 2012. Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491 (7424):393-398.