The Social Face of Genetics at the American Society of Human Genetics Meeting
By Bio-IT World Staff
October 14, 2015 | The American Society of Human Genetics (ASHG) has held an annual meeting every fall since 1948, five years before Francis Crick and James Watson first published the molecular structure of DNA. It would be hard to name a field of science that has gone through more turbulence than human genetics in that time. Once a largely theoretical field that occasionally pinpointed some crisp example of inheritance in rare disease, genetics is now spoiled for choice, diving through millions of variants in populations of thousands, and puzzling over the subtle effects of tiny, cumulative mutations. Geneticists who once looked at the shapes and sizes of whole chromosomes have gone on to sequence specific genes, then the whole human genome. The field has risen on the widespread hope that the Human Genome Project would bring new clarity to medicine, and fallen back into the messy reality of dealing with the complex results.
But in his address to the 68th annual meeting of the ASHG last Tuesday in Baltimore, the Society’s current president, Neil Risch of the University of California, San Francisco, brought up another aspect of his organization’s history: its treatment of women and minorities.
“I tried to take the job seriously, and I read the bylaws,” Risch told an audience of thousands gathered at the Baltimore Convention Center. “Here’s what it said, and I bolded it: ‘The President’s appointments shall, to the extent possible, reflect the diversity of the Society’s membership.’”
Risch, a statistician and data scientist by inclination, dug into the historical makeup of the ASHG’s Board of Directors. Over the course of the Society’s history, he found, over 70% of its board members have been men, and an overwhelming 97.5% have been white. Much of this, of course, reflects general trends in science and academia, and encouragingly, Risch also showed that the board has hovered at a little over 50% female for the past 15 years, reflecting overall ASHG membership.
But some of this disparity is surely tied to the unique baggage of the study of human genetics. From its earliest days, genetics has been dragged out to postulate unchanging, biological differences between races in traits like intelligence and behavior, a practice that Risch showed has still not been put to rest. In his presidential address, he brought up a very recent paper by Davide Piffer that sought to correlate different countries’ IQ scores with the frequency of seven genetic variants in their populations, on the premise that these alleles could partly determine human intelligence. The paper concluded, predictably, that African populations suffered for a lack of these “cognitive ability increasing alleles,” while European and Asian populations were enriched for them.
The fact that analyses like this are hopelessly compounded by socioeconomic variables, attempt to measure ill-defined traits like “intelligence,” and rest on completely mysterious mechanisms by which the genes in question might affect intelligence, has not dissuaded certain scientists from pursuing them right up to the present day. Instead, as Risch went on to illustrate, researchers have marched confidently into new minefields, as in the continuing hunt for a “gay gene.” “Have the genetic studies of sexual orientation really been so conclusive?” Risch asked, reviewing some past proposed biological markers for sexual orientation that have not panned out.
Throughout, Risch took on these topics with a light touch, a sense of humor, and the rigor of a statistician. At one point, he tried to find Piffer’s seven proposed IQ alleles in the DNA sequences of two public figures who have made their whole genomes public: James Watson and the Human Genome Project leader J. Craig Venter. Both of these white intellectuals, Risch observed, were notably lacking in the allegedly IQ-boosting variants.
But Risch was also attentive to the human toll of this scientifically propped-up prejudice, which the study of genetics seems uniquely susceptible to. He recalled that the groups whose collective traits geneticists have time and again tried to “explain” have too often felt dehumanized by the results.
“For us as geneticists,” he concluded, “what is most important is that genetics and geneticists should in no way contribute to those kinds of negative feelings.”
The Precision Medicine Initiative
Risch’s presidential address was a rare reminder, during a meeting to share new research and technologies, of the social responsibilities of science. The symposium that followed spoke to its social possibilities.
One of the biggest ongoing stories in American genetics is the Precision Medicine Initiative, a federally driven effort to collect genomic and health information on at least a million individuals, to promote better targeting of therapies to patients’ unique biology. At the ASHG meeting, Francis Collins, Director of the National Institutes of Health, followed Risch on stage to share updates on the heart of that project, the proposed National Cohort of one million Americans.
“It’s great to be back here at the American Society of Human Genetics, a society that has meant a great deal to me,” Collins said as he took the stage. “I attended the first one of these 36 years ago, and it changed my whole perspective… Having the chance to mix and mingle with people who were on the brink of making major revelations happen, in terms of how human genetic variation could be used to understand disease, I was captivated.” Collins, of course, went on to direct the national arm of the Human Genome Project, as opposed to the parallel corporate project led by Venter.
Building on that project now as lead organizer of the Precision Medicine Initiative, Collins is faced with a new set of challenges that are less technological than social and institutional. Because gathering the data for this initiative will have to be a massively distributed effort, new and rigorous standards will have to be introduced for collecting that data, sharing it, protecting the privacy of the patients who participate, and formatting it in a way that is mutually comprehensible across organizations. These are problems that have so far defeated our healthcare system, which is storing more and more medical data electronically but has never been truly successful at passing it between hospitals or research centers.
Moreover, members of the National Cohort should be easy to recontact for follow-up research, and should make their data available for broad use by qualified scientists. That requires new attitudes toward research consent. “[Patients] are much more interested in being engaged at the table, to have a role in the study design, and to have information coming back to them, not as passive subjects but as partners,” Collins said.
Collins shared key details of how the Initiative intends to reach its goal of signing on one million patients for a complex study of this nature. Radically, the NIH proposes to let any volunteer sign onto the National Cohort online, making their health information and, if possible, genomic data available to researchers involved in the effort. The push will also involve deliberate outreach to groups who have historically been little studied in genetic medicine ― including, through community health centers, the uninsured.
Collins also revealed two major departures from traditional consent procedures that the NIH plans to implement. First, when participants consent to join the National Cohort, they will be making their data open not only to an initial study, but to any future research connected to the project — without specifying in advance what that research might entail. This should smooth the way to involving hundreds or thousands of scientists with different research interests in genomic health studies at a massive scale, while preventing attrition from new rounds of consenting.
Second, a single Institutional Review Board will oversee the entire project, rather than leaving members to deal with conflicting standards at their various institutions. “You can imagine what kind of nightmare this would be otherwise, given the size of the enterprise,” Collins remarked.
Additional symposium speakers added more nuance to plans for the National Cohort. David Hunter of Harvard spoke about the huge barriers involved in leveraging EHRs, which still have little in the way of shared standards for measuring or even talking about health outcomes, for a shared resource like the National Cohort — while adding that, with a push toward new, common surveys and questionnaires, EHRs could potentially expand at least some aspects of the National Cohort to tens of millions of patients.
Naomi Wray of the University of Queensland looked at ways to gather genomic data efficiently at scale, urging researchers to consider imputing whole genomes from large SNP chips, rather than trying to sequence thousands of genomes at once. She also shared intriguing research on how much data can be recovered this way.
Perhaps most excitingly, Marylyn Richie gave an encouraging progress report from Geisinger Health System in Pennsylvania, which has entered a large partnership with Regeneron Pharmaceuticals to sequence tens of thousands of patients’ whole exomes. Talking up the advantages of approaching new study participants in the same health system that will collect and manage their data, Richie told the audience that this program has already consented 90,000 patients for research and completed 50,000 whole exomes, in a model where researchers can dig into participants’ EHRs, and where those participants can expect to be kept in the loop with information about the research being conducted. This cohort alone, if it could be made fully interoperable with a broader effort, would go a long way toward assembling the planned National Cohort.
“It is so exciting to have arrived at this point, to have this kind of support from Congress and the administration, and the opportunity to do something really profound,” Collins said in summary. “The potential here is really unprecedented.”
“Knowledge Is Not Enough”
It’s interesting to see genetics taking on such a public face at one of its most prominent meetings: owning up to its potential misuses, and speaking up for partnerships with research subjects that involve giving data back.
It was fitting, then, that ASHG decided to give its opening symposium on Thursday to three figures involved in public understanding of science: Atlantic correspondent Ed Yong, Story Collider executive director Liz Neeley, and blogger and activist Andrea Downing.
These speakers all came at their subject from different angles. Yong, a science journalist, spoke about his role as a watchman for overhyped discoveries and dangerous trends in science, such as the reproducibility crisis. Neeley, whose Story Collider podcast often takes a more human-interest-oriented tack to scientific stories, spoke about the joys of finding a narrative in a tangled web of research, and how scientists sometimes struggle to see the storyline in their own work. And Downing, who blogs about her experience living with a genetic variant to the BRCA1 gene that places her at profound risk for developing breast cancer, was most passionate and engaging when railing against damaging trends to patients, like the reluctance of genetic testing companies to share data, or the (now overturned) practice of patenting genes and mutations.
Yet they all shared in common the conviction that science needs something greater than “science communication,” merely transmitting new results to the public and cheerleading for the scientific enterprise. As Neeley showed from her interviews with working scientists, the community’s goals for addressing the public are actually split neatly between these “traditional” aims, and more “strategic” goals like building long-term trust.
That involves needling the social institutions built on science, like testing companies, to keep the public's interests at heart. It also involves an acknowledgement of the personal: the individual scientists who make discoveries, and the non-professionals caught up in the scientific process. As Downing conveyed in telling her own story, even the doubt and flux in science has a personal face. Receiving a hard-to-interpret diagnosis of a possible future illness, Downing said that she felt any decision she made was both unclear and controversial. “You hear knowledge is power, but the problem is, knowledge is not enough,” she said. “We [BRCA carriers] have so-called actionable genes that don’t feel actionable.”
In addition, said Yong, scientists need a friendly opposition that won’t take claims at face value. He told the audience that some of his favorite stories have taken to task sloppy or poorly-reported science, helping correct the record while also showing readers the scientific process in action. (True to form, Yong has already written a piece in the wake of the AHSG meeting that turns a skeptical eye on a new genetics of homosexuality study.)
For scientists who are dismayed at how their field is presented to the public, he said, the best way to help is to be a good source to journalists. Reach out with ongoing research that perhaps has not been tidied up into the format of a published paper yet. Get your views in the open through blogs or social media. And most of all, if asked to comment on others’ work, make the effort to be engaging, add context, and wrangle with flaws and limitations in a way that goes beyond “more research is needed.”
This should all be familiar to scientists, Yong observed. “What is peer review,” he asked, “if not criticizing each other’s work and holding it to the highest possible standards? And in many ways, journalism is the same.”
Many of these speakers’ presentations can be viewed on the ASHG meeting website. For Bio-IT World’s report on some of the new technologies on display at the ASHG meeting, see “New Products and Announcements at the American Society of Human Genetics Meeting.”