GENOME RESEARCH LIMITED
The students in John Burton’s grade 7 to 11 science classes have never lived in a world without knowledge of how the human genome is strung together. That their teacher was one of the people involved in unravelling this mystery means little to them. “I have told them, to try to generate enthusiasm, but have not gone into detail,” says Burton, who mainly teaches physics.
Fifteen years ago, as a member of the International Human Genome Sequencing Consortium, Burton managed one of the high-throughput production teams at the Sanger Centre. “The Human Genome Project (HGP) was a fantastic piece of work to be involved in, and we always felt that we were helping to leave a worthwhile legacy,” he says. Altogether, researchers from more than 40 institutions took part in this international effort, led by MIT’s Eric Lander.
The publicly funded consortium had commercial competition from Craig Venter and his company Celera, however, and in February 2001, both groups published first drafts of the human genome sequence. The consortium’s work appeared in Nature, and Celera’s article was published in Science the next day. Fifteen years and thousands of citations later, how have these landmark papers affected some of the more than 500 people on the author lists?
For many, the HGP marked the beginning of a career in genomics. Aoife McLysaght was a PhD student at Trinity College Dublin at the time, looking for whole-genome duplications in animals at the base of the vertebrate evolutionary tree. Now a professor of genetics at Trinity, she studies evolutionary constraints on gene dosage.
Human genomics has come a long way in 15 years, and so have the people who began the task of elucidating that sequence.
The project also motivated Andy Mungall and Bill Majoros, who were both inspired to start PhD programs after working on the sequencing efforts. Mungall enrolled in a PhD program to study genomic imprinting soon after co-leading the sequencing of chromosome 6 at the Sanger Centre. “I was keen to apply my genomics expertise to health care,” says Mungall, who now works at the British Columbia Cancer Agency in Vancouver. Majoros wrote a book on gene-prediction methods after developing gene-discovery software for Celera. Now he is a PhD student at Duke University Medical Center, where he studies how genomic sequence variants affect gene splicing. “The reference genome was only the beginning,” he says. “Extrapolating what we’ve learned about the reference genome to personal genomes is an exciting new frontier with enormous implications for health care.”
Several companies based on personal genomics have popped up in recent years, such as Invitae, which carries out genetic testing for hereditary disorders. Years back, Invitae cofounder Michele Cargill contributed to the population genetics section of Celera’s Science paper, which taught her more than just genomics. “I learned to work with people from different disciplines and learned to not avoid efforts that seem impossible.”
The project also helped Kimmen Sjölander, who developed algorithms to assign genes to functional subfamilies while at Celera. “The paper in Science increased my visibility, allowing me to return to academia.” Sjölander is now at the University of California, Berkeley, where she studies the evolutionary development of new functions and structures across protein superfamilies. She points out that we still don’t really understand what all the genes in the human genome do. “We have a serious problem with the accuracy and information content of gene functional annotations. Since functional annotations are foundational to biomedical research, this problem has to be addressed.”
It’s a problem that extends to other organisms’ genomes. A few years ago, Kevin McKernan’s company Medicinal Genomics sequenced the cannabis genome, to better understand the plant’s pharmaceutical potential. McKernan has been involved in genomics for years. He was team leader for R&D at the Whitehead Institute during the HGP, and afterwards started various companies focused on sequencing technologies. One of these systems was acquired by Life Technologies, where McKernan worked for several years. When he left, he was asked to sign a noncompete agreement, which led him to start working on the cannabis genome instead. McKernan is now CSO at Courtagen Life Sciences—a medical genetics testing company founded by his brothers—which acquired Medical Genomics in 2011.
External circumstances also steered the career path of Trevor Woodage. At Celera, he was involved in genome annotation and single nucleotide polymorphism (SNP) analysis, but when a move to Minnesota left him with little choice in scientific jobs, he retrained in patent law. Now, Woodage is an associate attorney at Fish & Richardson, in the Twin Cities. “I’ve had the opportunity to work on a number of patent litigation cases, primarily in the life sciences,” he said. “I’ve worked on some cases that have overlapped with some of the work that I did at Celera, but more often, the cases have involved drug development.”
Neha Desai (née Garg) made a big career change as well. “I was especially interested in ensuring children have no fear of math.” She worked on template preparation and marketing at Celera, but now runs a Mathnasium franchise in Arlington, Virginia, offering math tutoring to kids. “One of my biggest goals is to see more children go into STEM fields, especially girls.”
Human genomics has come a long way in 15 years, and so have the people who began the task of elucidating that sequence. Some are now working on annotating the genome or developing new techniques, others are educating the next generation or taking their scientific experience elsewhere, but all of them have been shaped by their contribution to science history. “Being part of such an obviously important project at such an early career stage was very exciting,” says Trinity’s McLysaght, “and that type of excitement motivates me still.”