Gregg Johnson is trying to outlive his family history. To do that, the 57-year-old textiles artist has had a colonoscopy every year since the mid-1980s. Each time, doctors remove upward of 150 tiny polyps in hopes of preventing colon cancer. Johnson lost his mother, Sandra “Sammy” Moon Johnson, to metastasized colon cancer in 1983 when she was just 47 years old. Her mother also died from the disease, at age 42, just like dozens of others on the branches of Johnson’s family tree. “We’re cancer magnets,” Johnson says.
Johnson, who lives in Salt Lake City, keeps his health closely in check thanks in part to University of Utah scientists and researchers who tapped his family for genetic testing and cancer studies more than 20 years ago. Tests confirmed what the family essentially already knew: Their biological lineage includes a genetic mutation that predisposes them to colon cancer and can be traced back to a single English couple who emigrated to America in the early 1600s. The U’s research study, which stretched over a dozen years and included data on hundreds of Utahns, helped investigators unlock critical genetic coding linked to APC— adenomatous polyposis coli—a syndrome characterized by the early onset of colon cancer, says Deborah Neklason PhD’99, research assistant professor of oncological sciences at the University of Utah Medical School and director of the Utah Genome Project. The data and health protocols, when paired with a clinical intervention, including genetic counseling, testing, and regular colonoscopies, have helped reduce familial cancer rates for Johnson and others. “We have prevented almost all the [potential] cancers in that family,” says Neklason. “This is about a change in behavior and awareness. This is an incredible story of the impact of genetic testing.”
For decades, U researchers and investigators have played a critical role in identifying pieces of the genetic puzzle that continue to change the face of medicine, from understanding how some diseases work to improving patient diagnoses, medical outcomes, and daily health management. At the same time, researchers and patients have been watching court cases, involving Myriad Genetics and the U Research Foundation, proceed over patenting of some of that research and related questions about future studies, as well as public access to genetic testing and personalized medicine. The outcome of those cases is factoring into the future course of the research.
Genetics is the study of how specific traits and characteristics are biologically transmitted to us by our parents. Formed by deoxyribonucleic acid, or DNA, genes are the physical units of heredity that are carried on our chromosomes. Scientists believe each person’s body has about 20,500 separate genes, the totality of which is known as the genome. Isolating those genes has helped scientists identify anomalies that either cause or increase our risk for some diseases. Over the past four decades, advancements in genetic research have provided enormous insight into the workings of the human body and the causes of disease, says Lynn Jorde, chair of the U Medical School’s Department of Human Genetics. Genetic tests can indicate if a person is a carrier for a disease or if an unborn child will have genetic conditions. “It gives us the potential to treat disease more efficiently and, in some cases, even to prevent disease altogether,” says Jorde, whose own research includes the genetic basis of both hypertension and human limb malformation.
University of Utah researchers can claim dozens of key discoveries in genetic and molecular medicine, including genes responsible for more than 30 diseases, such as melanoma, atrial fibrillation, hypertension, macular degeneration, and neurofibromatosis. U scientists also are credited with developing key tools in bioinformatics to help further understanding of how genetic material works. “The University of Utah is great at this, and they have been for a long time,” says Lawrence Brody, chief scientific officer at the Maryland-based Center for Inherited Disease Research at the National Human Genome Research Institute. “The faculty there has made fundamental contributions to human genetics.”
Brody attributes Utah’s critical mass of talent to two factors: significant philanthropic funding to support genetics research, and a population of large families with a Mormon church-supported predilection for genealogy work, which has provided a trove of family history to aid in genetic study. The University houses the Utah Population Database, with some 20 million records that layer family genealogies with state demographic records, including data on births, deaths, cancer rates, and other medical diagnostic and treatment records. It is the only resource of its kind in the United States and the largest such database in the world. The church/state partnership provides records on about 7.3 million individuals, some of whom can be linked to 11 generations of relatives. The database—supported through the generous financial assistance of the Jon M. Huntsman family, the Huntsman Cancer Foundation, and the Huntsman Cancer Institute—has enabled about 100 research studies, allowing investigators to analyze patterns of genetic inheritance and identify specific genetic mutations.
Genetic data are instrumental in the development of personalized medicine. Knowing what’s in a person’s genome allows physicians and patients to make more informed health care choices, Jorde says. To date, scientists have been able to link about 4,000 diseases to mutated genes, according to the American Medical Association. Yet genetic testing still has many limitations, Jorde says. The testing, which is done through sampling of tissue, blood, or other body material, can only provide a predictive risk assessment, and then only for some diseases. Test results can be missed or misinterpreted. In some cases, research and technology may not yet exist to explain some genetic mutations, even though those mutations can be identified. “People think, well, I can just get genetic tests and find out everything about me, all of my predispositions to everything,” Jorde says. “In reality, genetic testing, while it can be very useful in certain contexts, only reveals predisposing factors. Sometimes they can be very powerful predictors; sometimes they can be only approximate predictors.”
The biomedical community can sometimes contribute to public confusion about the power of genetic testing, in part because researchers “want to say this is important and useful,” Jorde says. That’s where some in the research community become uncomfortable with companies that offer direct-to-consumer genetic tests that in many cases are for diseases for which the genes haven’t actually yet been identified, such as the gene for bipolar disorder.
Questions about commercial genetic testing were at the center of the 2009 lawsuit against the Salt Lake City-based biotech company Myriad Genetics, the University of Utah Research Foundation, and their partners. Filed by the American Civil Liberties Union on behalf of more than 20 plaintiffs, including medical associations, researchers, health advocates, and patients, the case asked one central question: Can a human gene be patented? More specifically, ACLU attorneys challenged whether the U.S. Patent and Trademark Office should have issued a patent on the tumor suppressor genes BRCA1 and BRCA2 to Myriad Genetics, which was founded in 1991 by a team of scientists, including then-U genetics researcher and medical professor Mark Skolnick.
One of the first companies to examine the relationship between genes and human disease, Myriad was created to develop genetic tests based on research from the U, including Skolnick’s work to isolate the BRCA1 and BRCA2 genes. The U Research Foundation, which facilitates commercialization of faculty inventions from many academic disciplines, later licensed Skolnick’s discoveries to Myriad. Over two decades, Myriad has paid its BRCA patent partners—the U, the Hospital for Sick Children, Endorecherche Inc., and the Trustees of the University of Pennsylvania—8 percent of its annual profit in the form of royalties, or more than $57 million, Myriad spokesman Ron Rogers says. The U’s share of the royalties has amounted to more than $40 million over the years as of last fall and is used to support further research and education programs at the University, according to Tom Parks, the U’s vice president for research.
Certain variations in the BRCA1 and BRCA2 genes signal a person’s risk for some hereditary forms of cancer. Women with a BRCA mutation face a 36 to 85 percent lifetime risk of breast or ovarian cancer. In men, BRCA gene mutations are linked to breast and prostate cancers. The BRCA genes earned wide public attention in May 2013 after film actress Angelina Jolie announced she had undergone a bilateral prophylactic mastectomy following genetic testing. Jolie lost her mother to both breast and ovarian cancers.
In the lawsuit, ACLU attorneys claimed the patents on the BRCA genes gave Myriad, which didn’t license the patents to other researchers, an unfair monopoly on the genes and their associated genetic information, as well as the predictive tests for the mutations, which at roughly $3,000 could be too expensive for some patients. ACLU attorneys argued the exclusivity was a civil liberties issue because it “limits the public’s right to benefit from scientific breakthroughs that advance medical research,” court documents state. “This monopoly has a chilling impact on other researchers’ ability to conduct medical research, undermining advances toward better treatment, cures, and more accessible, affordable genetic testing. … Such a monopoly serves to profit one company at the expense of the public good.”
Myriad attorneys argued that patents have been used for more than 100 years, across all kinds of commercial economies and industry, to provide a critical incentive for investment in innovation and discovery. “Research is a very expensive proposition,” Myriad attorney Ben Jackson says. “Companies have to spend millions of dollars to make these discoveries. But more importantly, to bring these discoveries to the average person, companies need incentives.”
The U.S. Trademark and Patent Office has issued thousands of gene patents since the early 1980s as the pace of genetic research and discovery exploded. By 2005, nearly 24,000 genes had been identified, and more than 4,300—20 percent of the whole human genome—had been claimed as intellectual property. In the early days of genetic discovery, academic researchers, private labs, and biotech companies all sought out patents as a means of preserving future commercial opportunity, even if they weren’t quite sure about the value of their work. “Twenty or so years ago, [patents] really helped push people a little bit forward,” says Brody, of the Center for Inherited Disease Research. “There was a rush to find the genes that were responsible for the major diseases, and because they were patentable, they were patented. They were staking out turf.”
But patents proved troublesome and less profitable for most in biomedicine, says Brody. In most cases, patent holders found “there was little money to be made” from the claims they had staked on specific, single genes, he says. Researchers also found that the patents were barriers to advancing their scientific discovery.
As a young researcher, molecular geneticist Elaine Lyon says she found herself stymied many times in the lab because she kept bumping into patents in her work on a test to identify a protein that metabolizes drugs in the body. In some cases, Lyon wasn’t even studying the specific patented gene but was still blocked because the area of her interest was part of a genetic sequence that fell under a patent’s umbrella. “At this point, I was getting more and more frustrated,” says Lyon, who is now the director of molecular genetics and genomics at ARUP, an anatomic pathology reference laboratory on the University of Utah campus.
Lyon says many in the molecular science industry have been long opposed to patents and see them as a disincentive to innovation and a barrier to helping patients. The royalty fees associated with using patented genes have also contributed to stalling research by driving up costs or making the tests that resulted from research too expensive for patients, says Lyon, who is also president of the Association for Molecular Pathology. The association’s members had mixed opinions about the Myriad case, but Lyon says she shared the views of one colleague who said no matter the outcome, “it would be best for the field if we just had this decided once and for all.”
The unanimous decision from the U.S. Supreme Court came on June 13, 2013. The court ruled that genes cannot be patented, because they are a product of nature. “Myriad did not create anything,” Justice Clarence Thomas wrote in the court’s opinion. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.”
The decision invalidated Myriad’s five patents associated with BRCA genes and has similar implications for other gene patents that have been issued over the years. But the court did not leave researchers or biotech companies entirely without opportunity or incentives for competition. The ruling says patents can apply to cDNA, or artificially constructed DNA that contains some section of isolated, natural genomic DNA. Innovations in medical research technology and development in disease testing processes would also likely be patentable.
Whether the court’s decision will squelch investment and commercial development isn’t clear, although it may cut into the profits of biotech companies by increasing competition. On the same day the ruling was announced, two companies said they would immediately begin offering their own BRCA tests to the public. At least five related lawsuits remain pending.
Another potential impact: Research universities that have partnered with private companies to take their discoveries into the commercial marketplace may suffer some financial losses. Revenues from royalties, which are paid in exchange for licensing rights, could drop, Myriad’s Jackson says. “Any university should be concerned about an alternate, broad reading of the court decision.”
Jackson believes the court’s opinion is “appropriately narrow,” but also not entirely timely. “Gene patenting is in its twilight,” he says, because most of the important gene discoveries were made prior to 2001, when the Human Genome Project, which has mapped the entire human genome, first began publishing its findings.
Brody agrees that Supreme Court case was somewhat oddly timed, considering the fizzling competition for gene discovery, but he still believes it will have a significant impact. “I think it’s an important decision, because it allows individuals and companies to go forward and use the genetic information to innovate and invent new things without worrying about whether you’re on somebody ’s turf,” he says.
Neklason, at the U Medical School, says that if the ruling had come 10 to 15 years earlier, it might have made the research climate “more collaborative and less competitive,” but neither she nor Jorde believe it will have much effect on the day-to-day mission of U genetics investigators. “No matter what, you are going to see some competition; scientists are competitive people,” Jorde says.
Currently, U scientists are involved with at least nine ongoing research studies in medical genetics, such as projects to identify high-risk genes for childhood cancer, and assessing cancer risks for diseases with known cancer genes, including psoriasis and arthritis, chronic obstructive pulmonary disease, and familial atrial fibrillation. In addition, more than a dozen new projects are beginning this year, including studies on the genetics of Lou Gehrig’s disease, genetic susceptibility to spontaneous pre-term birth, and locating a “thinness” gene to prevent obesity.
Meanwhile, the effects of the Supreme Court ruling should help drive down the costs of gathering genetic information, ultimately benefiting patients in terms of both access and overall health and well-being, U researchers predict. Currently, it costs about $8,000 to have a private lab produce a person’s entire genetic sequence—far less than in the past, and about the same price Myriad charges now to run just the two BRCA gene tests. In the future, sequencing could cost even less.
For his part, Johnson believes knowing more about his genetic health is saving his life. Not a fan of doctor visits or pill popping, the father of two boys says his increased awareness about genetic factors has also led him to gently nudge many of his friends to seek testing. “I’ve outlived my mom by a number of years, so from my perspective, this is saving my life,” he says. He’s also grateful to know that in some small way, his family ’s history and participation in research work will likely help many others. “My mom was very gracious and giving, and she was always thinking about others,” says Johnson. “I’m sure she’d approve.”
—Jennifer Dobner, a former longtime Associated Press reporter and editor, is now a Salt Lake City-based freelance writer and a frequent contributor to Continuum.
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