Tying diseases to DNA in thousands of women
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Starting from the disease and working back to the DNA, a team of academic, government and industry researchers hopes to discover the genetic causes of breast cancer, heart disease and a host of other common disorders affecting women.
The novel collaboration, which involves Brigham and Women's Hospital in Boston, the National Institutes of Health and the biotechnology giant Amgen Inc., will analyze DNA collected more than a decade ago from 28,000 participants in the Women's Health Study, combing it for differences between those who have developed serious illness and those who have remained healthy. Researchers believe the results will eventually enable physicians to better predict a woman's risk for disease and to tailor more effective treatments.
The project is part of a new gold rush sweeping medical research aimed at uncovering the genetic underpinnings of common diseases using new DNA-reading technologies. The joint involvement of corporate, government and academic players underscores the increased interest in translating existing genetics research into practical medical knowledge. But it also raises thorny questions about how to patent and commercialize discoveries stemming from publicly funded research efforts.
The comprehensive gene map created by the Human Genome Project provided a one-size-fits-all map of human genes. But each person's DNA varies slightly, which accounts for each person's unique appearance -- and unique susceptibility to disease. The scientists' goal now is to link those DNA variations to who gets sick and who doesn't.
The Women's Health study is one of several federally funded research projects for which participants provided blood samples years ago that now constitute a potentially rich resource to match genetic variations with disease on a large scale, a new approach called a "whole-genome association study."
Because huge amounts of data are involved -- the new initiative will look at 317,000 different variations from each person's DNA -- the cost of scanning the genes significantly exceeds what the NIH and academic institutions can afford. That has prompted academic scientists to seek support from private industry.
"We're entering a time where scientific projects are becoming larger and more complex," says Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Harvard Medical School and the principal investigator for the study. "To unlock the genetic information we can use to improve the health of our patients and our understanding of what causes disease is going to require very large projects and expertise from many kinds of individuals."
Previously, scientists have discovered the genetic causes of scores of rare, inherited disorders, including cystic fibrosis. But for most common diseases, the genetic risk factors still aren't known. Indeed, scientists expect that for everyday problems like diabetes, many genes may play a variety of contributing roles, making the genetic culprits more difficult to identify. Researchers hope the new approach will help because it permits broad, speedy searches in a person's DNA.
Amgen will buy equipment that will allow it to create individualized genetic profiles for each of the study's 28,000 women participants. The company will provide the data to Dr. Ridker, who, with colleagues at Brigham, will match it against clinical data from the same women. The expectation is that similar genetic variations will turn up in women who have developed, say, osteoporosis, and perhaps different variations will show up among those whose bone density is in good shape. In that way, researchers can zero in on the genes associated with those conditions.
It's unclear just how valuable the information from genome scans will be in identifying new therapeutic targets or speeding new drug discoveries. But the Women's Genome Health Study may provide an answer sooner than other similar efforts. Many newer studies have only recently collected DNA from participants or have just begun the task, so it may be years before enough subjects in those studies develop serious diseases.
But several thousand of the 28,000 women in the new study have already been diagnosed with important common diseases or conditions: About 900 have developed breast cancer; 1,000 have had a heart attack or other major cardiovascular event; 2,500 have developed osteoporosis and 1,400 have suffered broken bones; and 1,200 have diabetes.
"We don't have to wait for follow-up," Dr. Ridker says. "We just have to get the genomics started."
But as both academic centers and companies begin investing significant sums for studies that may reveal the genetic underpinnings of society's most costly diseases, tough questions loom over who will control and have rights to commercialize the discoveries.
Under the terms of the new project, called the Women's Health Genome Study, results describing associations between genes and diseases will be posted in a public database through the NIH and made available to any scientist interested in conducting further research. "The overwhelming primary aim is to get the vast amount of these data in the public domain as quickly as possible so they can immediately advance patient care," Dr. Ridker says.
Once in the public domain, the genetic associations can't be patented, but scientists could use them as a springboard to research how to develop diagnostic tests and treatments that could be patented. "The purpose of this is to make a contribution to the global knowledge base," says Joseph P. Miletich, Amgen's senior vice president, research and development. "Amgen isn't looking for any rights to anything."
That reflects the view of the NIH that the basic links between genes and disease are such a fundamental discovery that patenting them should be discouraged. The NIH is developing guidelines for genome-wide association studies that are expected to emphasize that policy, but it has no firm rule against patents.
The new study "might be an interesting test case" of how academic scientists and industry should work together on such projects, says Elizabeth Nabel, director of the NIH's National Heart, Lung and Blood Institute. The NHLBI is contributing $4 million in grant support over five years to Dr. Ridker's study.
The NIH recently launched a similar effort, with a $20 million donation from Pfizer Inc., that will study several conditions, including asthma, in a group of 18,000 patients. The aim in this case is also to make data on gene-disease links available in a public database. "This is the beginning of a number of major studies in which genome-wide scans are going to be conducted," Dr. Nabel says.
But in other circumstances using other technology, academic and corporate scientists alike have filed patents on such data. Several companies have built lucrative businesses around such discoveries, including for gene-based diagnostic tests. Meantime, last month, tensions erupted over a plan by a private hospital to study the DNA of 100,000 children after an Icelandic gene-hunting company sued to halt the project.
Dr. Ridker and Dr. Miletich maintain that posting the study results in a public database will preclude almost any foreseeable efforts to patent gene-disease associations identified in the study. But if that does happen, Amgen says it would have nonexclusive rights to discoveries based on the data, with the option in certain circumstances of paying for exclusive rights at full market value.
"It is the second and third levels of work that are ultimately where new targets and new drugs might come from," Dr. Ridker says. "If you don't collaborate to get the first layer of data out there for the public, I don't see how you can get to the next layer."
Once the NIH guidelines are finalized, possibly by next spring, Dr. Ridker and Dr. Miletich say the intent is for the new study to comply with them.
First Published October 24, 2006 12:00 am