With advances in computing and sequencing technology, science has been riding the wave of the Human Genome Project, ushering in a new era where genetic information will greatly impact science, medicine and society. Anticipating this new era, Duke University developed a unique response to the Genome Age: The Institute for Genome Sciences and Policy.
|Institute for Genome Sciences and Policy Director Huntington F. Willard.
Huntington F. Willard, the Nanaline H. Duke professor of genome sciences at Duke University, notes that genetics holds a certain kind of mystique for people that most other sciences do not have.
“I describe it as being similar to an expecting parent seeing their first ultrasound,” he says. “It’s just a fuzzy image, but it immediately evokes a sense of wonder about life. Genetics is like that; if I hand you a copy of your genome, you can look at it much like that developing baby. That’s your code; your characteristics and traits, not to mention a snapshot of both your past and future— that’s very powerful stuff.”
And, in today’s world, the idea of looking over your genetic makeup is not a far-fetched one. With advances in computing and sequencing technology, science has been riding the wave of the Human Genome Project, ushering in a new era where genetic information will greatly impact science, medicine and perhaps, most importantly in Willard’s eyes, society.
Anticipating this new era, Duke University developed a unique response to the Genome Age: The Institute for Genome Sciences and Policy.
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|When Huntington F. Willard was an undergraduate at Harvard University, reading "Arrowsmith" by Sinclair Lewis helped put the science he was learning into the bigger context of what it meant to be a scientist.
Willard, who moved to Duke in 2003 as the founding director of the institute, recalls an unusual moment back in his undergraduate days at Harvard in the early 1970s that set the tone for his future career. He was taking the biochemistry class that originally had been developed by James Watson. It was the usual hard slog for both premeds and pre-science majors, but what was unusual was that halfway through the semester, they suddenly stopped learning just hard-core science and instead read two novels: “The Double Helix” by Watson and “Arrowsmith” by Sinclair Lewis (about the life’s journey of an up-and-coming scientist).
“It took me for a loop at first, but later, it really helped me put the science I was learning in the bigger context of what it meant to be a scientist, both in the world of science and in the world of society,” he says. He kept that broader view throughout his career, as perhaps unconsciously reflected on his office shelves by a host of books on scientific ethics and philosophy that he has read over the years.
Therefore, he immediately was intrigued when he was approached by Duke almost nine years ago to head its new and unique vision for an interdisciplinary campus-wide institute that would bridge science and society.
“They basically gave me a blank piece of paper to work with and a license to be a bit schizophrenic, going back and forth between these two worlds,” he says, “and I went for it.”
And today, the IGSP has grown to include nearly 100 affiliated faculty members across the university, spanning virtually every sector of the campus. In addition to individuals in various science, engineering and medical departments, the IGSP boasts members from the departments of African and African American studies, philosophy, English and mathematics as well as the schools of business, law and public policy. This extremely diverse group works together under a tri-fold mission: to uncover the biology and evolution of our genome, to reflect on its meaning for individuals and to push that knowledge to the front steps of both medicine and social policy.
It’s a steady climb that can be attributed to both nature and nurture.
Part of the ability for the IGSP to work, Willard notes, lies in Duke’s DNA. It’s a nationally and internationally known academic institution that has a strong academic reputation in multiple schools like arts and sciences, medicine, law and business, all nicely contained within a fairly compact campus where different disciplines spill over freely. “You have to look pretty hard to find boundaries here,” Willard says.
At the same time, Willard has been instrumental in bringing the right personalities along for the ride for the past several years, whether they were pre-existing faculty or new hires.
“Sometimes, I’ve had to be blunt to prospective faculty,” he says. “They had great credentials and skills but also had that tunnel vision about their own research, which wasn’t the kind of personality we look for at IGSP. So, I’d tell them that I knew they would succeed in their career; it just wouldn’t be here.”
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|A view of the Fitzpatrick building that houses many of the IGSP labs and offices.
Assistant professor Laura Rusche is one of the scientists who took the IGSP bait; in fact, she was one of the trailblazers, arriving in 2003 as one of the IGSPs first external recruits following her postdoctoral fellowship with Jasper Rine at the University of California, Berkeley.
As she talks about her own work using yeast models to understand how DNA and various proteins assemble into discrete active and silenced chromatin domains, the view from her office provides a sense of the wide breadth of IGSP’s scientific enterprise, which encompasses six component centers that study and teach genes and genomes from the molecular to the population level: genomic medicine, systems biology, evolutionary genomics, computational biology, applied genomics and technology and genome ethics, law and policy.
Directly across lies Linchong You, a biomedical engineer who designs synthetic gene circuits in bacteria to try to program specific cellular behaviors, while nearby sits the office of Greg Crawford, who has developed bioinformatics technologies that can identify DNase I hypersensitive sites (an indicator of an active DNA regulatory element) from potentially any species and cell type with a sequenced genome.
“It can be a little bit of a struggle for us to all come together because the perspectives of our members are so different— and we’re all pretty busy— but we definitely have the opportunities and desire to forge strong and diverse relationships.”
The opportunities arise from regular seminars, journal clubs and meetings that cover the wide breadth of this institute, not to mention the dozens of potential research collaborations. (And, if all else fails, Willard has been known to host dinners to directly introduce investigators who might need to get acquainted.)
Rusche has taken full advantage of this great environment in her own research. As a postdoc, she had worked with an unusual gene called SUM1, which coded for a promoter-specific repressor, and found that a single amino acid change created a mutant that could silence new and different regions.
“And, that got me thinking about where new protein function comes from,” she says. “After I came here, I started talking with an IGSP colleague, Fred Dietrich, whom I was introduced to by Hunt over dinner during my interview. He has been characterizing the genomes of various fungi related to traditional yeast, spanning hundreds of millions of years of evolution. And, with that information, I’ve started looking at the evolution of Sir2 histone deacetylases, to see how function has changed over time.”
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Evolution is a vital component of the IGSP as well; even though the institute has grown to a sizable and sustainable level, Willard notes it’s not a time to rest on one’s laurels. “The genome sciences continue to advance at a rapid pace, and we have to move as well because if we’re not climbing that mountain, we’re rolling down the hill.”
Keeping the momentum involves placing future bets and thinking ahead. That includes a strong emphasis on education, and, as such, the IGSP offers a number of options at the student level, from introductory courses for incoming freshmen to undergraduate summer fellowships featuring mentored research and engaging activities, to a certificate-level program, equivalent to a minor degree in genome sciences and policy (a comparable graduate level certificate currently is in the works, to broaden and connect the two doctoral programs the institute already offers).
|Proteomics Core Director M. Arthur Moseley and his team hard at work helping the IGSP mission.
On the research end, one of the most recent initiatives has been setting up a top-level proteomics facility, a commitment that reflects Willard’s broad view that the genome sciences are much more than “just” DNA.
American Society for Biochemistry and Molecular Biology member M. Arthur Moseley, brought into the IGSP in 2007 to head the new proteomics facility, compares this view with shining light through a diamond. “Depending on which facet of the diamond you look through, you’ll see a different image,” he says. “You need to see all of them to get a complete picture.”
“Likewise, genes are only what might happen; messenger RNA is what is trying to happen; and proteins are what does happen. Only by looking at all the ‘-omic’ technologies can we understand mother nature’s subtleties.”
In just three years, Moseley has built his core from the ground up— “literally,” he says, "when I arrived, I didn’t have a floor or walls or anything”— to feature six state-of-the-art tandem mass spectrometers and a dedicated team that now has supported more than 80 investigators (in the IGSP and Duke University at-large) and 180 projects.
The proteomics core is just one of several technology platforms established within the IGSP to expedite the genome-related research efforts of the institute. Under the astute operational eye of technology manager and fellow ASBMB member Thomas Burke, whom Moseley describes as the glue that holds the diverse IGSP platform technologies together, the institute offers services for DNA microarrays, genome sequencing, RNA interference screening and an extensive fluid and tissue biospecimen facility.
“The IGSP is the ideal environment for platform technologies at Duke,” Moseley says. “Hunt created the infrastructure required to successfully deploy them to studies in basic and translational sciences, including a major investment in specialized IT infrastructure that enables user-friendly access to all the technologies.”
And, although the various technology cores primarily are service facilities, they contribute much more than just running samples. “We provide opportunities for all the core directors to apply their interests to various research projects,” Burke says. “We encourage them to meet with faculty, sit in on lab meetings and help implement methods or strategies to problems. We want our technology members to feel involved in the institute’s mission.”
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Robert Cook-Deegan, who heads up the institute’s Center for Genome Ethics, Law and Policy (GELP), echoes Burke’s assessment. “A lot of schools say they have interdisciplinary institutes,” he says. “But, I think it’s a testament to Hunt and Duke University that we really strive for that here.”
Cook-Deegan, a former physician and molecular biologist who switched to a policy career after doing an American Association for the Advancement of Science science and technology policy fellowship, highlights his own center in those feelings; despite being somewhat different than the other five IGSP centers in that GELP’s mission is not focused around laboratory work— though his center does carry out independent research projects— he feels that GELP is given equal status with the rest of IGSP.
And, this is important, because among all of IGSP’s parts, GELP provides that extra spark that helps make IGSP a unique fixture among academic centers.
“Duke certainly wasn’t alone last decade in seeing that genomics was the next big wave barreling in to shore,” Willard points out. “But, most research places seemed fixated on the impact of genomics strictly from a health and medicine perspective.”
“We weren’t going to try to out-Broad the Broad Institute,” he adds. “So, instead, Duke saw an opportunity to carve out a niche in merging the genome sciences with genome policy.”
At GELP, Cook-Deegan and his colleagues, a group that includes individuals trained in policy, law, business, bioethics and genetic counseling, follow the IGSP motto of “Ask Big.” Their goal is to analyze questions emerging from the world of genetics and genomics that matter in the real world— for example, how companies that offer direct-to-consumer genome sequencing should be regulated— to help people make better decisions. Given that genome policy falls under such a big umbrella, GELP has specialized in a few key topics such as intellectual property, informed consent and consumer genomics.
It’s not a “think tank” per se, though Willard and Cook-Deegan hope that some of the research that comes out of GELP could be used positively by those in policymaking positions— and perhaps soon, for as big an impact as genomics has made the past few years, the next incoming wave is even bigger.
“As recently as a year ago, we only had a handful of complete human genomes sequenced,” says Cook-Deegan, “but even now, scientists are sequencing hundreds every week, and all the speculation of the $1,000 genome is becoming reality.”
“And, once that’s completed, I think it will open the floodgates and completely change how we look at, interpret and value our genetic data.”
Nick Zagorski (firstname.lastname@example.org) is a science writer at ASBMB.