Research

Research

Guiding the Future of Genomics

When Watson and Crick discovered the double helix of DNA 50 years ago, the possibility of mapping the human genome sequence seemed like an impossible task.

But now that hurdle has been cleared, and researchers and policymakers were forced to ask the question, "Where does genomics research go from here?"

In 2003, the National Human Genome Research Institute addressed that question with "A Vision for the Future of Genomics Research," a planning document published in Nature that outlined scientists' and public health officials' ideas for the direction of genetic studies. The NHGRI, a division of the National Institutes of Health, held nearly two years of intense discussions with scientists and members of the public in preparation for drafting the document.


	Geneticist and pediatrician Dr. Bonnie Pagon with one of her young patients.

Eleven UW scientists participated in drawing up the plan, which delineated three main areas of the research: the relation of genomics to biology, health, and society. The document envisions genome research as a three-story building made up of those areas of study, perched atop the foundation of the completed Human Genome Project.

If the philosophy of genome research is a building constructed from the field's different areas of study, the part of the building representing the ethical, legal, and social implications of genetics is a vertical pillar providing support to all floors of the structure.

That's because all of the main areas of genetics research are tied in one way or another to ethical, legal, and social implications (ELSI). The ELSI Research Advisors, a committee chaired by Dr. Wylie Burke, professor and chair of medical history and ethics, and adjunct professor of medicine and epidemiology at the UW, is advising the NHGRI on taking those implications into account when drafting public and genome research policies.

ELSI appears in many aspects of genome research, from concerns of potential discrimination based on genetic testing results to questions about restricting access to genetic data.

"Intellectual property issues may be very important, as will research funding issues," said Burke. "I think it's clear we're reaching a time when we'll need large databases with genetic information that's cross-linked with patient information. There are privacy and confidentiality issues associated with that effort."

But ethical questions also come up in unexpected areas, such as whether or not patients should be informed of their inherited traits and conditions. Though at first glance it seems logical that a patient should be told they have predisposition for a disease or condition, that may not be the case.

"If we find out someone's predisposed to diabetes, we tell them the same things we tell everyone else: exercise, eat right, and so on," explained Burke. "So what's the value of that information? Will it, in fact, motivate a health lifestyle? How much is that information detrimental, since it may cause fatalistic approaches?"

The group is also helping direct attention to where it's needed in genome research and policy. Some areas, such as intellectual property, still need in-depth research before policies and guidelines can be drafted, while other areas, such as the implications of genetic testing, are further along in research.

"There's been a fair amount of work looking at the implications of genetic testing," Burke said. "Now might be the time to talk about writing guidelines."

That's when the ELSI Research Advisors can help bring together experts for a workshop on drafting policy guidelines. In the case of intellectual property issues, the group can advise further research.

"We provide advice in turning goals into concrete approaches," Burke said. "We can help NHGRI to determine the need for requests for grant applications, or RFAs, in areas in need of further research."

In addition to Burke's contribution to the ELSI Research Advisors group, many other UW faculty members took part in drafting the NHGRI's plan for genome research, including Dr. Melissa Austin, professor of epidemiology; Robin Bennett, genetic counselor and manager of the UW Medical Genetics Clinc; Dr. Philip Green, professor of genome sciences; Dr. Arno Motulsky, professor of genetics and of medicine in the Division of Medical Genetics; Dr. Debbie Nickerson, associate professor of genome sciences; Dr. Maynard Olson, professor of genome sciences and of medicine in the Division of Medical Genetics; Dr. Bonnie (Roberta) Pagon, professor of pediatrics; Dr. Scott Ramsey, associate professor of medicine in the Division of General Internal Medicine and member of the ELSI Research Advisors; Dr. Elizabeth Thompson, professor of statistics and biostatistics; and Dr. Robert Waterston, professor and chair of genome sciences.

The NHGRI planning document calls for 15 "grand challenges" meant to spur a great move forward in genome research, such as developing a detailed understanding of the heritable variation in the human genome, creating strategies for identifying genetic contributions to disease and drug response, and drafting policies for the use of genomics in medical and non-medical settings.
"It's an ambitious document," Burke said. "It's intended to be an ambitious document. They are called 'grand challenges' for a reason."

One area of genetic research that generates public interest is the impact that the research will eventually have in real-world applications, such as gene therapies, disease screenings, and drug treatments. Many researchers have moved in that direction, since much of the initial gene sequencing work has been completed under the Human Genome Project.

"Across the spectrum of genome research, there's a lot of effort to figure out concretely, 'What does this mean?'" Burke said. "It's clear that there's a vision among genome scientists to develop molecular tools for basic understanding of disease biology."