Returning Individual Research Results to Participants: New NASEM Report

Posted By: Jillian Galloway, MS, Science Policy Analyst, ASHG

As you may recall, last year, the National Academies of Sciences, Engineering, and Medicine (NASEM) was asked by the Centers for Medicare & Medicaid Services (CMS), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) to evaluate the many issues and perspectives surrounding ‘the return of individual-specific research results generated in research laboratories’.

In recent years, there has been significant discussion among scientists about the return of results to research participants. As geneticists and genomicists discover information of potential clinical benefit to participants, they are considering when it is appropriate to share such information with participants.

Consensus Study Report
NASEM Report: Returning Individual Research Results to Participants: Guidance for a New Research Paradigm

In keeping with the trend towards greater participant inclusion, the recently launched All of Us program promises to share individual-level data with participants. By signaling greater involvement in the research process and dubbing All of Us participants as ‘partners’, NIH hopes to make participation more valuable and equitable.

Given this context, the NASEM committee was charged with evaluating the ethical, social, regulatory, and operational issues associated with returning results to participants. With many members involved in such research, ASHG submitted comments to the committee that focused on the complexity of returning individual-specific results of genomics research, outlining areas of consensus and contention within the genomics community.

The NASEM committee’s report, released last month, aligns with ASHG’s comments in some ways as well as revealing meaningful differences of perspective. For example, ASHG recommended that research funding include financial support for returning results to participants to make the task more viable. However, the NASEM report calls for research institutions and funding agencies to “develop and provide access to the resources and infrastructure needed to ensure that investigators conducting testing…can meet the necessary standards for quality”. Overall, NASEM’s report emphasizes addressing the quality of results over the burden to researchers in operationalizing their return.

The committee recommends placing greater responsibility on researchers returning individual-specific research results. It also proposes several guiding principles for researchers: chiefly, that the return of results be considered from the inception of the study, through its design and development, and that laboratories that plan to return results adopt high-quality standards.

However, the committee acknowledges that the diversity in size, funding, and scale of research laboratories makes CLIA certification, the clinically required regulation for laboratories issuing any test results to individuals, at times inappropriate or unnecessary for returning results not intended to inform clinical care. To address the financial, logistical, and operational hurdles of returning high-quality laboratory analyses with confidence, the committee suggests the creation of an accepted quality management system for research laboratories as an alternative to CLIA certification.

The NASEM report also outlines the many scenarios and variables determining whether laboratory quality is sufficient for investigators to return individual research results. In addition, the committee calls for the continued assessment of participant preferences and values, echoing ASHG’s comments.

In summary, while the committee’s recommendations may increase the frequency of returning results, and thereby enlarge the demands upon researchers, they are in keeping with the general scientific move  towards increasing researcher responsibility for the respect, trust, and needs of research participants.

ASHG will continue to monitor the activities of the various agencies to see how and to what extent they will adopt the recommendations set forth by the NASEM committee.

Jillian Galloway, MS, is a Science Policy Analyst at ASHG. For more information on ASHG’s policy priorities and activities, visit the Policy & Advocacy website. 

Bringing Us Closer to Understanding Health and Disease at an Individual Level

Guest Post: Ed Ramos, PhD, All of Us Research Program

The National Institutes of Health supports groundbreaking research and biomedical studies that seek to enhance and improve health. On May 6, it took a big step in pushing the envelope further by launching the All of Us Research Program.

20180705_EdRamos
Edward Ramos, PhD, All of Us Research Program, NIH (courtesy Dr. Ramos)

Currently, people joining the program will have the choice to answer questions about their demographics, overall health, and lifestyle behaviors. Participants will also be asked, but not required, to authorize access to their electronic health record data, which is a significant source of clinical information about a person’s health history. We have established an expanding network of clinic sites around the country where some participants will be invited to give physical measurements and biospecimens for future assays and research. The program plans to begin genotyping and sequencing participant DNA next year.

All this data will be stripped of obvious identifiers and made available to researchers, who could range from students and citizen scientists to established investigators. They’ll have to apply to access the information and abide by a data use agreement. Also, participants will be able to access their own data and see how researchers are using it. All of Us is building the data resource now and expects it to be open for research in 2019. The resource should grow quickly as data from electronic health records, genetic analyses, wearables, and other sources are added.

The All of Us Research Program recognizes that the information participants are providing is personal and sensitive, and security and privacy are of the highest importance to the program. The program is working hard to establish and maintain a secure infrastructure that supports a participant-focused recruitment and enrollment process. For example, the program has implemented security features that meet rigorous federal standards for protecting and securing data.

So what is my role in all of this? As someone who has spent several years exploring human genetic variation as it relates to disease and drug response, I would love to be on the receiving end of all this data! I play an equally exciting part in All of Us as the program director of The Participant Center, which manages overall operations for All of Us’s “direct volunteer” enrollment across the country. The Participant Center has established a phenomenal set of national partners, such as Walgreens, Blue Cross Blue Shield, WebMd, and Fitbit. These partners are helping expand our national reach for clinic sites, developing national and local marketing and outreach strategies, and exploring data collection through various digital health technologies.

While my research interests align with All of Us’s scientific vision, I always find myself most attracted to this program for personal reasons. I lost my father to pulmonary fibrosis, helped my mother control her diabetes, and have stayed up many nights trying to alleviate my son’s asthma. Perhaps it’s safe to say that many of us, maybe even all of us, have similar stories. I’m honored to be a part of something that could potentially bring us one step closer to better understanding health and disease at an individual level.

Edward Ramos, PhD, is a member of the All of Us Research Program at the National Institutes of Health. He has a PhD in Molecular Biotechnology and was the 2006-2007 ASHG-NHGRI Genetics & Public Policy Fellow.

Biology of Genomes 2018: The Past and Future of Genomics

Posted By: Emily C. Glassberg, PhD Candidate, ASHG Communications Committee

A few weeks ago, I attended the 31st annual Biology of Genomes (BoG) meeting at Cold Spring Harbor. In addition to highlighting the amazing research that comprises the current state of genomics, this meeting highlighted the storied past and bright future of the field. The enthusiastic participation of attendees, both at the meeting and on Twitter, shows incredible energy and momentum as we try to understand the genome’s role in biology, evolution, and disease.

20180607_BoG
Attendees network at Biology of Genomes 2018 (Credit: Constance Brukin; copyright CSHL)

Genomics Present

The seven scientific sessions covered functional genomics, medical genomics, computational genomics, and evolutionary genomics, as well as genome engineering. Seeing this varied body of work at a single meeting clearly demonstrates that theory, experiment, high-throughput screening, and countless forms of new technology and data analysis all play central roles in shaping our current understanding of the human genome.

And, while the human genome was the primary subject of study, non-human genomes got coverage as well. Highlighted research included the genomes of near relatives, like Neanderthals; to those of best friends, like dogs; to those of model organisms, like yeast. Crowd favorites included Jaemin Kim’s and Elaine Ostrander’s talks using dogs as a system to learn about the genetic basis of complex traits (for the science as well as the adorable pictures).

The scientific programming also included two keynote speakers, Wendy Bickmore and David Page. Bickmore discussed her group’s work on how 3D chromatin structure relates to the mechanism by which enhancers – particularly long-range enhancers – interact with promoters to regulate gene expression.

Bickmore’s emphasis on the need to assay enhancer function in vivo was echoed elsewhere at the meeting. In particular, Emma Farley spoke about high-throughput measurements of enhancer function in the model chordate Ciona. In combination, these talks sparked a conversation about whether current computational models are looking in the wrong places when it comes to predicting enhancer activity and specificity.

Page presented his group’s work on the evolution of sex chromosomes with an eye to understanding sex differences in health and disease. Page’s question of whether and how males and females “read their genomes differently” connected to broader questions that recurred throughout this year’s meeting –  how do we understand the genome dynamically? When and how does the same genome lead to different outcomes?

The ways in which the genome and its downstream effects change over time and space is a big open question, and this year’s BoG showcased many approaches to tackling it:

  • Ben Strober and Jonathan Griffiths both used time-course gene expression data to track how gene regulation changes throughout cellular differentiation and development.
  • Jake Yeung shared an example of dynamic chromatin interactions and rhythmic promoter-enhancer contacts that are connected to circadian rhythm.
  • Christina Leslie presented work on how the chromatin state of tumor specific T-cells changes during cancer progression and how that influences disease treatability.

And that’s just a sample of the exciting work in this space! While we don’t yet have clear answers to these questions, the research discussed at BoG reveals a landscape that is complex, nuanced, and fascinating. What a great time to be in genomics!

Genomics Past

In addition to discussions spanning the range of the current field of genomics, BoG included a brief talk in memoriam of molecular and developmental geneticist John Sulston, who passed away on March 6, 2018. Dr. Sulston was well known for his seminal work in the now-model organism C. elegans, as well as his role in the Human Genome Project. Eric Lander also toasted Jim Watson for his role in the Human Genome Project, and to celebrate his 90th birthday. Lander and other BoG organizers later apologized for the toast, as it was seen by many in the community as minimizing Watson’s history of racist and sexist commentary.

Genomics Future

And, finally, no meeting would be complete without a vision for the future of the field.

A panel on the Ethical, Legal, and Social Implications of genomics research included four perspectives on the promises and pitfalls of germline genome editing. While there is considerable excitement around using CRISPR to cure genetic disease, many issues remain regarding proof of safety as well as ensuring equal access to the technology. Following a lively discussion during the question-and-answer, the consensus seemed to be that germline genome editing is a distant future. In the meantime, we can focus on the application of currently available options, like genetic screening and assisted reproductive technologies.

The National Human Genome Research Institute (NHGRI) also engaged researchers in its current strategic planning initiative, which began in February 2018 and will be completed in 2020. NHGRI is collecting input on priority areas to help the institute live up to its mantra, The Forefront of Genomics.

Of course, the scientific discourse at Biology of Genomes isn’t limited to the talks. The three lively poster sessions were great opportunities to exchange ideas. And many spirited discussions took place during the coffee breaks, over the traditional Cold Spring Harbor banquet, and down at Blackford bar. All told, there’s a lot to look forward in genomics!

Emily C. Glassberg is a PhD Candidate in the Department of Biology at Stanford University. She serves on ASHG’s Communications Committee and has been an ASHG member since 2014.

Developing a ‘2020 Vision’ for Genomics

Guest Post By: Eric D. Green, MD, PhD, Director, National Human Genome Research Institute

The National Human Genome Research Institute (NHGRI) recently launched a new round of strategic planning that aims to establish a ‘2020 vision’ for genomics research. This ~two-year effort will position NHGRI to lead genomics research and its applications to human health and medicine in the new decade – keeping the Institute at the Forefront of Genomics.

20180605_EricGreen
Eric D. Green, MD, PhD, Director of NHGRI (courtesy NHGRI)

The strategic planning process will emphasize discussions about emerging areas of genomics that are not well-defined, are poised to benefit from new investments, and are not specific to specific diseases or physiological systems. These include broadly applicable areas such as genomic technology development; genomic variation and its role in human disease; medical use of genomic information; and the ethical, legal, and social implications of genomics, among others. We will also focus on areas in which NHGRI expects to continue providing leadership with others, including the genomic bases of rare and common diseases as well as computational genomics and data science.

A key aspect of NHGRI’s strategic planning process will be engaging both experts and diverse public communities for input, especially given the increasing relevance of genomics in everyday life – from non-invasive prenatal genetic testing to the growing availability of consumer genomics.

The new NHGRI strategic plan will be published in October 2020 – specifically to commemorate the 30th anniversary of the launch of the Human Genome Project.

We hope that you will participate in this strategic planning process! In the coming months, NHGRI will be hosting workshops, town halls, social media conversations, and satellite meetings at scientific conferences. We have already held a virtual town hall, have upcoming events in Seattle, Palo Alto, and Atlanta, and will host a satellite meeting at the ASHG Annual Meeting in San Diego in October.

Anyone can now submit their ideas on the Institute’s dedicated strategic planning website on genome.gov and follow conversations on Twitter and Facebook using the hashtag #genomics2020.

We look forward to engaging with all of you as we collectively shape the future of genomics. See you in San Diego!

Eric D. Green, MD, PhD, is the Director of the National Human Genome Research Institute (NHGRI) at the U.S. National Institutes of Health (NIH), a position he has held since 2009.

Celebrate DNA Day 2018 with ASHG

Posted By: Jannine Cody, PhD, Chair, ASHG Information & Education Committee

Happy DNA Day! Every April 25, we commemorate the discovery of DNA’s double helix structure in 1953 and the completion of the Human Genome Project in 2003, two key milestones in genetics. A variety of DNA Day events are taking place worldwide and online, including the debut of our ’15 for 15′ infographics on recent advances in human genetics – check them out!

ASHG marks this date each year by announcing the winners of our Annual DNA Day Essay Contest. Open to high school students worldwide, this year’s contest asked students to share their views on whether medical professionals, such as medical geneticists or genetic counselors, should be required for all genetic testing, or if consumers should have direct access to predictive genetic testing.

We received over 1000 entries from 43 U.S. states and 23 countries. Essays went through three rounds of scoring by ASHG members, who selected a first, second, and third place winner as well as 10 honorable mentions. (Want to participate next year? Read Dennis Drayna’s blog post on the judging experience.)

The winning essays were thoughtful and nuanced, reflecting a variety of views and a sophisticated consideration of the issues, and we were excited to see high-quality entries from several countries around the world. We awarded first place to Diane Zhang, a junior at Fox Lane High School in Bedford, N.Y.; second place to Ilan Bocia, a senior at YULA-Boys in Los Angeles, Calif.; and third place to Nadia O’Hara, a freshman at Pechersk School International in Kyiv, Ukraine.

This slideshow requires JavaScript.

For a full list of winners, honorable mentions, and teachers, and to read the winning essays, check out the DNA Day 2018 Winners. Through this contest and our other K-12 initiatives, we hope to encourage young people to explore genetics and inspire the next generation of ASHG members and leaders.

Jannine Cody, PhD, Professor of Pediatrics at the University of Texas Health Science Center at San Antonio, is Chair of ASHG’s Information & Education Committee. Learn more about ASHG’s K-12 education programs.

ASHG and FASEB: Working Together to Make a Difference in Advocacy & Policy!

Posted By: Jennifer Zeitzer, FASEB Director of Legislative Relations

The Federation of American Societies for Experimental Biology (FASEB) is the nation’s largest coalition of biomedical researchers, representing 30 scientific societies and more than 130,000 researchers from around the world. As a member of FASEB, ASHG works closely with FASEB and the other member societies to advance research and education in biological and biomedical sciences and advocate for increased funding for biomedical research. Through FASEB, ASHG also monitors and regularly speaks out on science policy issues impacting the scientific community.

20180419_JenniferZeitzer
Jennifer Zeitzer, FASEB Director of Legislative Relations

For example, ASHG recently joined FASEB in celebrating the historic $3 billion dollar increase for the National Institutes of Health (NIH) approved by Congress in late March. Securing the increase was a collaborative effort between many organizations. ASHG urged its members to email and call their elected officials and sent two Board members to FASEB’s Capitol Hill Day to make the case for NIH funding with their members of Congress.

This month, Congress began consideration of the fiscal year (FY) 2019 budget, and ASHG and FASEB are again working together to advocate for increased NIH funding. There is a good chance NIH will receive another significant funding increase in FY 2019, thanks to legislation passed in February to raise strict spending caps that were enacted in 2011. The appropriations committees will determine how that additional funding is divided among federal agencies.

Making sure NIH gets another increase will require additional coordinated advocacy between ASHG and FASEB over the next few months. More information is forthcoming, but ASHG members should expect to receive e-alerts from FASEB as well as reminders to check out the resources and tools in the ASHG Advocacy Center.

ASHG members also have access to FASEB’s Advocacy Toolbox, which includes instructions for requesting a meeting with a member of Congress at home and tips for communicating with elected officials through social media. The Washington Update newsletter provides the latest news on science policy and advocacy inside the Beltway and from federal agencies (click here to subscribe).

Communicating about science is another area where ASHG partners with FASEB. The Human Microbiome and Individualized Medicine: Genetically Fine-Tuning Prevention, Diagnosis, and Treatment of Disease are articles in FASEB’s Breakthroughs in Bioscience series that illustrate genetics-related developments in biomedical research and their importance to society. Similarly, the Horizons in Bioscience one-pagers, including articles on liquid biopsies, CRISPR/Cas gene editing, epigenetics, and optogenetics, summarize scientific discoveries on the brink of clinical application and supplement the longer Breakthroughs.

The recent $3 billion increase for NIH and other advocacy successes would not have been possible without the joint effort between FASEB and its member societies. As Congress makes decisions about the 2019 budget, FASEB is proud to have a strong partnership with ASHG to ensure that the voices of scientists are heard on Capitol Hill and in congressional districts across the country.

Jennifer Zeitzer has been the Director of Legislative Relations at FASEB since 2008. She coordinates advocacy efforts with FASEB member societies and others in the biomedical research community, including organizing FASEB’s annual Capitol Hill Day.

FASEB offers free webinars on advocacy and policy issues. Sign up to receive notifications about future FASEB webinars here.

Representing ASHG and Genetics at FASEB’s Capitol Hill Day

Posted by: Neil Hanchard, MD, PhD, ASHG Board Member

I don’t consider myself to be particularly ‘political’; however, the last two Presidential budgets have included closing the U.S. Department of Agriculture-funded building that houses my lab and office. This has made me keenly aware that the science we do doesn’t occur in a vacuum. I thus consider myself particularly fortunate to have had the opportunity to participate in FASEB’s Capitol Hill Day (March 8) as a representative of ASHG. This now annual event brings scientists from across FASEB’s 31 experimental biology societies – including ASHG – to the Capitol to lobby for their own science. It’s timed to coincide with annual budget making season and, since it’s been going on longer than any of the more than 50 fellow scientists in the room knew for sure, it’s a central piece of FASEB’s public policy engagement.

20180315_FASEBHillDay
L-R: James Musser, FASEB President-elect; Sharma Prabhakar, AFMR; and Neil Hanchard, ASHG Board Member.

For me, getting up close and personal with the machinations that enable the science engine was a truly fascinating experience. The DC-based staff of FASEB and ASHG essentially do this all the time and, accordingly, were like a well-oiled sequencer. They did an amazing job of prepping first time scientists-come-lobbyists (like myself) – hosting prep sessions well before the event, as well the night before and morning of. Plus, they ensured that everyone was suitably armed with critical talking points for their State representatives and glossy summary pamphlets to go along with them. After a day running around (literally) meeting with State representatives’ aides in the halls and offices of the National’s Capitol, here are my top 5 takeaways:

  1. There is strength (and comfort) in numbers. FASEB represents ~130,000 scientists in the U.S. and around the world – that’s not a trivial number and the powers-that-be know it.
  2. The Capitol is very large. It’s a mind-boggling maze of offices and hallways, with a subway linking the two houses to boot. With multiple 10-15 minute meetings strewn across the “The Hill”, there’s no way we could have done it on our own – the FASEB facilitators, who included our own ASHG staff, knew not only where we were going, but each of the representatives’ voting and stances on science issues as well.
  3. There is an art to the lobby. There’s an etiquette to lobbying, with polite, often unwritten rules of how to deal – the mandatory exchange of business cards (which I forgot – whoops!); the pitch, the pivot (when you’ve lost your audience); the parting promises and closing invitations – a well-rehearsed dance that, performed well, can be the difference between a “yea” and a “nay”.
  4. Everyone wants their piece of the pie. The Lobby dance is performed by umpteen groups this time of year – if there’s a group you can think of, they were probably there. For scientists to get the funding they need to continue doing good science, they should remember that “the squeaky wheel gets the grease.”
  5. Science is bipartisan. Somewhat surprisingly for me, the pitch for NIH, NSF, and USDA science was well-received at all of the Texas representatives’ offices we visited, irrespective of party affiliation. I also learned of several unheralded champions for science from both sides of the political aisle.
20180315_FASEBHillDay-meeting
After a chance hallway meeting with Rep. Al Green, the Texas group sat down with Rep. Green’s staffer to discuss the importance of biomedical research.

All in all, this was a truly enlightening and emboldening experience; honestly, if I can do it, pretty much anyone can, and there’s a strong argument that any and all scientists should – host a representative in your lab, visit your local representative’s office, make the phone call/sign the email – as jaded as I was about the process at the start, it was heartening to know that it can actually make a difference.

Neil Hanchard, MD, PhD, FACMG, serves as Early-Career Member of the ASHG Board of Directors. He is an Assistant Professor and Clinical Geneticist at Baylor College of Medicine and Texas Children’s Hospital, and has been a member of ASHG since 2010.