BETHESDA, Md. _ Although the discovery of the long-sought afterbreast cancer gene, BRCA1, won't yield meaningful benefits for cancervictims for years, it is a clear scientific triumph.BRCA1 is believed to be responsible for approximately 5 percent of allcases of breast cancer (about 600,000 women in the U.S. carry adefective BRCA1 gene) and about 25 percent of cases diagnosedbefore the age of 30. The other 95 percent of all breast cancer cases arebelieved to arise from multiple mutational events that occurspontaneously over the course of a lifetime.On Wednesday, National Institutes of Health (NIH) officials hailed thediscovery, saying it represented the "best in American science," amassive collaborative effort engaging 45 scientists from industry,academia and the government.Mutations in BRCA1, a novel tumor suppressor gene located onchromosome 17, produce susceptibility to breast and ovarian cancer.Since a 1990 research paper predicted the existence and whereabouts inthe human genome, BRCA1 has been a holy grail for competing teamsof geneticists all over the globe.Researchers from privately held Myriad Genetics Inc., of Salt LakeCity, the University of Utah, the National Institute of EnvironmentalHealth Sciences (NIEHS), Eli Lilly & Co. and McGill University havewon the race to isolate BRCA1 and will publish the results of theirresearch in the Oct. 7 issue of Science. The Science paper suggests thatthe gene may also play a role in ovarian cancer.A hastily organized press conference here on Wednesday followed apre-emptory news release which appeared in some of the lay press.NIH officials and researchers emphasized that the cloning andcharacterization of BRCA1 is a scientific achievement that will takeyears to trickle down into the general population and benefit theaverage cancer victim. In addition to giving researchers prognosticability for the relatively rare inherited forms of breast and ovariancancers, the finding could ultimately unlock the secrets about howcancer itself progresses."In the last eight years, researchers have discovered 12 tumorsuppressor genes. This is an extremely exciting time in science," said J.Carl Barrett, chief of the NIEHS Laboratory of MolecularCarcinogenesis. "But the finding creates as many questions asanswers."If successfully developed, a genetic screening test for mutant BRCA1could identify women at high risk for heritable breast cancer. Armedwith that knowledge, women would still face a range of unsavorytreatment options, from the disfigurement of a prophylacticmastectomy to the risks of increased surveillance."We don't know how to respond to genetic information," cautionedNIH Director Harold Varmus. "We are now one step closer to devisinga test that will be useful in making a prognosis for some women, butthis finding does not bear upon treatment strategies for breast cancervictims or upon women who get a diagnosis of breast cancer from amammogram procedure."Francis Collins, head of NIH's National Center for Human GenomeResearch, said that use of a BRCA1-derived test for breast cancersusceptibility should be confined to the research community for"several years" with "appropriate informed consent." His comments, aswell as, those of breast cancer activists, raised questions about thefuture commercialization prospects for presymptomatic geneticsusceptibility testing.It's unclear whether the highly politicized issue will spawn a new set oflegislative or regulatory controls and how pricing paradigms willevolve for tests that may have to go hand-in-hand with geneticcounseling services.The BRCA1 discovery is a high profile success for the tiny, three yearold Myriad Genetics. Since its inception in May 1991, the firm hasraised a total of $11.3 million from institutional and individualinvestors. One of its founders, Mark Skolnick, has been working on theBRCA1 puzzle for more than two decades and led the research team atMyriad and the University of Utah. He is an author on both of theBRCA1 papers to be published in October _ one describing the gene'sisolation and another describing four germline mutations of the genefound in breast and ovarian tumors.Claiming The PrizeAccording to vice president of finance, Jay Moyes, Myriad has alreadyfiled a plethora of patents to stake out its intellectual property position,including composition and matter patents for BRCA1 and its potentialfuture uses as a therapeutic and diagnostic tool. The Utah firm haslicensed worldwide development and commercialization rights toBRCA1 therapeutic applications to pharmaceutical giant to Eli Lilly.The two firms will collaborate on the research and development. Inaddition, the Lilly subsidiary Hybritech will develop diagnostic kits.It could be years before a reliable diagnostic kit is ready and as long asa decade before meaningful treatment might arise from the BRCA1discovery. Development of a screening test will be complicated by thefact that BRCA1 is a large and complex gene.In addition, according to P. Andrew Futreal, an NIEHS scientist whocollaborated on the BRCA1 effort, there is "no rhyme or reason" towhere the harmful mutations occur along the gene.The National Breast Cancer Coalition (NBCC), an advocacyorganization headquartered in Washington, expressed concern onWednesday that a presymptomatic genetic test for heritable breastcancer will hit the market within two or three years."We may soon have a test that will tell a woman she may have as muchas an 85 percent chance of getting a disease for which there is noknown cure and which she cannot prevent," said NBCC president FranVisco. "We do not yet have legislation in place to protect women whotest positive for the gene from discrimination in employment andinsurance coverage. Because we have failed to enact meaningful healthcare reform, the existence of this test will lead to more women beingdenied coverage for breast cancer."Visco said the test should not be developed or widely distributed beforeits efficacy is proven. "Any test developed from these findings must besubject to rigorous research studies: "we need to find out how well thetest works and what is the best method of monitoring and counselingwomen who are found to have the gene," she said. "Until that time, weinsist that the FDA not approve the test and its availability should belimited to those families who agree to participate in peer-reviewed,approved research protocols." n091594BRCA1

-- Lisa Piercey Washington Editor

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