The Evolution & Medicine Review

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Charlie Nunn weighing in here with a commentary on Joshua Schiffman’s plenary talk.

Those of us at the ISEMPH meeting in Durham experienced a fantastic and inspiring plenary talk by Joshua Schiffman, of the Huntsman Cancer Institute and the Intermountain Children’s Hospital in Utah. His talk highlighted the value of comparative research, the effectiveness of case studies, and the ways that biomemetics is relevant to questions in evolutionary medicine.

Josh started with a case study of a young girl, Danielle, with cancer. She was found to have Li-Fraumeni Syndrome, which confers an overall lifetime risk of cancer of about 80-90% (substantially higher than the 50% risk that most of us experience). Often these cancers involve early onset of bone and soft tissue cancers, such as sarcoma. This effect arises from loss of one of the alleles in the P53 gene, which plays a role in controlling cancer. As Josh put it, P53 is like a “superhero” of the genome. One-half of all human tumors are known to lack a functional copy of P53.

Josh then expanded the perspective to consider the emerging importance of comparison in oncology. He reminded us of the famous quote by Rudolf Virchow, “Between animal and human medicine there is no dividing line, nor should there be.” He went on to describe research led by Matthew Breen (NC State University) on naturally occurring cancers in dogs, and how Matthew has used the inbred genetic background of dogs to investigate the genetic drivers of cancer. Findings of identical genetic associations in dogs and people suggest targets for understanding and controlling cancer with new therapies.

Josh then segued to the important example of Peto’s paradox, namely that species of different body size exhibit similar rates of cancer. This finding is paradoxical because one would expect a positive association, with larger bodied animals expected to exhibit a higher rate of cancer, given that more cell divisions would have occurred. For example, one would predict that elephants have much higher rates of cancer than mice. Why, instead, are rates relatively constant across species, irrespective of body size?

With this excellent background, Josh shared his compelling results that copy number of P53 is one of the factors that helps reduce cancer risk in elephants. In particular, he and his colleagues found that elephants have about 20 copies of this “superhero” gene, as compared to just one for humans, and they produce more protein from these extra copies. In experiments involving exposure of cells to radiation, they further showed that elephant cells die at a higher rate (apoptosis) than human cells. The death rate in elephants was about five times higher than in those with Li-Fraumeni syndrome.

The talk ended with a description of Josh’s efforts to turn this exciting comparative finding into a new cancer therapy involving elephant P53 proteins, with exciting results to share. His trials aimed at applying this finding to help cure human cancer are still at an early stage, yet we all left with a strong sense of how a rigorous comparative approach can lead to new cancer therapies. Very exciting!