The "Narval" Biology
In this excerpt from a 2016 letter of recommendation, our science advisor Dr. Ting Wu (Professor of Genetics at Harvard Medical School), explains how she came to lend her research on ultraconserved elements of DNA to ANYA.
I was introduced to Carylanna and Jacob in October of 2014 by Amy Brown, Program Coordinator of The Science & Entertainment Exchange, when they asked for help in finding a geneticist to advise them on their screenplay. They emailed me a treatment of their screenplay and a series of questions about speciation, fetal DNA testing, and plausibility of their premise, asking also for advice on a specific mutation that might lead to speciation.
It took no more than a few seconds for me to be drawn in. First, the level, sophistication, and intricacy of their questions surpassed all others I had ever been asked by writers in the industry. Second, it was clear that, if produced, this storyline would raise public awareness of genetic technologies as well as enhance dialog between scientists and nonscientists, an outcome that would align well with pgEd. [Note added for clarity: pgEd is a public education and engagement group, founded by Dr. Wu in 2006, to increase awareness and conversation about the benefits as well as the ethical, legal, and social implications of genetics.] Finally, it occurred to me that several intriguing observations my laboratory had made about the human genome would work well for the story line.
In brief, my group studies one of the most baffling discoveries to emerge from the genome era – ultraconserved elements (UCEs), which were first published by Gill Bejerano and David Haussler in 2004 and have been baffling geneticists ever since. UCEs are DNA sequences scattered across our genome that, amazingly, have been maintained essentially unchanged for 300 to 500 million years, appearing today exactly as they were when birds, reptiles, and mammals diverged.
Because researchers do not know of any function that requires such conservation, the mere existence of UCEs is one of the greatest mysteries to emerge from the genome era. Breaking rank from other models, my group has proposed that the astonishing capacity of UCEs to persist unchanged may contribute to how genomes resist disruption, ultimately contributing to speciation and, thus, being of relevance to Carylanna and Jacob's story line. True, UCEs remain one of the most unexplained parts of our genome, and it will be years before we find out whether we are right or wrong, but I think that makes the entire story line even more interesting. Indeed, ANYA may generate the kind of speculation that may one day contribute clarity to the puzzle!
I am impressed with how Carylanna and Jacob have been able to distill the complexities of UCEs into palatable nuggets of information, all without losing any of the tantalizing aspects of these genomic gems, and then weave everything into a larger, highly plausible, backstory on how the Narwhal species split from the general human population. Currently, their story involves mutation of UCEs in the fascinating FOXP2 gene and a long period of isolation and genetic drift, all of which will resonate with human geneticists studying mutation rates as well as with population biologists studying speciation. The plausibility of their story line reflects their commitment to science and getting the basics right. No surprise, here, as Carylanna has a doctorate in anthropology and has taught genetics and evolution, and Jacob works with National Geographic as a producer and story editor on science-heavy shows about animals. Together, they have made the documentary Painting the Way to the Moon, an earnest portrait of a mathematician that clearly shows the often messy process of scientific discovery.
Finally, I will mention that Ruth and I are truly enjoying working with Carylanna and Jacob as they build the backstory, brainstorming with them about the pros and cons of specific solutions to plot problems. For example, Ruth suggested that the story implicate FOXP2 after another faculty member in our department, George Church, pointed out that it would be very likely that the general public would not value the uniqueness of a new, visually indistinguishable species if the difference between the newly discovered species and "us" were a small change in DNA sequence that did not have any noticeable effect on the individual. That is, why care if a gene therapy that allowed interspecies couples to reproduce would eventually wipe out the Narwhal species if there were no downside, no loss, no tragic consequence? As music was already part of the script, our conversation led quickly to the idea of giving the Narwhal a unique and magnificent musicality related to the FOXP2 gene, which is already known for its role in regulating speech. In other words, by focusing the story on UCEs located in the FOXP2 gene, the story line would make clear that any attempt to override the UCEs through gene therapy (such as via the exciting new technology called CRISPR) to restore reproductive fitness to interspecies matings would wipe out the precious, and now endangered, musicality of the Narwhals. Our guess is that people would now care.*
At present, individuals in the United States are protected against genetic discrimination by the Genetic Information Nondiscrimination Act, which was pushed through Congress by Congresswoman Louise Slaughter and signed by President Bush in 2008, but the need to consider potential future laws that would govern the alteration of human germ lines is now being debated in earnest. We are only at the beginning of this period of intense deliberation, and I think that ANYA, if produced, would play a significant and important role in preparing the general public as well as encouraging individuals to participate.
*UPDATE: While FOX-P2 is not mentioned onscreen, it is still part of the Narval’s biology. It also led us to film at Carnegie Mellon University, via Ruth McCole’s colleague, FOX-P2 researcher Andreas Pfenning.