What Difference Does Difference Make? An ASHG/FASEB Event on Diversity in Science

Posted by: Nalini Padmanabhan, MPH, Communications & Marketing Director, ASHG

Shirley Malcom
Shirley M. Malcom, PhD

“Diversity is a scientific imperative,” said Vence Bonham, JD, in his introductory remarks to last week’s ASHG/Federation of American Societies for Experimental Biology (FASEB) event, titled “What Difference Does Difference Make?”. The event featured keynote speaker Shirley M. Malcom, PhD, Head of Education and Human Resource Programs at the American Association for the Advancement of Science (AAAS), who led an informative, interactive, and spirited discussion among nearly 70 staff at ASHG, FASEB, and several other FASEB member societies.

With strong board support, ASHG is already undertaking steps within our community to improve diversity and inclusion in science and exploring additional efforts. By sharing ideas and feedback with AAAS, FASEB, and other scientific societies, who face similar challenges and operate in similar environments, we are committed to building on successful strategies to raise our collective effectiveness.

Diversity in Genomics Research and Among Researchers

Dr. Bonham, Chief of the Health Disparities Unit at the National Human Genome Research Institute (NHGRI), set the stage by describing the importance of diversity in genomic research cohorts and in the genomics workforce. He cited several studies showing that the vast majority of genome-wide association studies (GWAS) and genetics-based disease studies in the public domain focused on populations of European ancestry. Though there has been some change in recent years, he noted, populations of African, Latin American, and Asian ancestry are still significantly underrepresented.

Diversity in the scientific workforce follows similar patterns, he explained: data show the relative representation of African American scientists declines at each step along the career path, from graduate school applicant all the way through department head.

Access to Scientific Opportunity, Power, and Science as a Human Right

“The challenge we have in this country is that we are both too polite and too impolite. There are things we don’t talk about because it makes us uncomfortable, and part of the challenge we have had is that we have not been honest in our discourse,” said Dr. Malcom, framing her discussion. “Inequalities related to sex, gender, race, and ethnicity are all part of the same issue, which is the distribution of power. We don’t talk about power much, but it drives much of what we see that we do not like,” she explained.

The 1948 Declaration of Human Rights, recognized explicitly by most countries, includes the right to the benefits of scientific progress. Furthermore, she said, scientific curiosity is part of being human, and unequal access to a scientific career reflects differences in power within the field and the educational system. For example, those who set the research agenda define which questions the field considers important, how findings are assessed, and how success is attained. These decisions tell an implicit story about what science is, who science belongs to, and who can do science.

Dr. Malcom & Dr. Bonham
Dr. Malcom & Dr. Bonham lead a Q&A

Diversity Discussions Have Improved but Challenges Remain

Taking a historical perspective, Dr. Malcom traced how discussions of diversity have evolved since the 1960s and 1970s. Originally considering it solely as a legal issue related to civil rights, many started to improve inclusivity out of need – demographic shifts and a growth in research required more talent in the workforce. More recently, there is growing appreciation of the educational value of diversity as well as the innovation driven by a variety of perspectives and experiences.

“Today, women are the majority of students in higher education but not of the faculty,” she said. “There’s a mismatch between who is there and who teaches them, which affects the climate of the classroom. We need to create a new normal.”

Structural barriers and biases impede progress toward that new normal. These include difficulty in finding community and cultivating a sense of belonging, systematic undervaluing from faculty and peers, and a false assumption that difference equals deficiency.

That starts from admissions, she explained. “We have to get to a point where our programs recognize potential, not previously demonstrated performance, because not everyone has had the opportunity to actually be able to be successful in tests that we use to measure.”

Strategies and Current Efforts to Improve Diversity

Given these challenges, what can scientific societies do to improve diversity? Dr. Malcom offered several practical strategies. These include several activities that are increasingly front and center for ASHG. This year, we are beginning to track and emphasize greater diverse representation in our Annual Meeting program, and are working actively to promote more nominations and inclusion of diverse candidates for roles in society leadership and awards.

ASHG also will be exploring ways we can leverage and share with the field the learning, resources, and strategies of other leading groups, including SEA Change, an AAAS effort to support diversity and inclusion in STEM, especially in colleges and universities. It focuses on science departments and programs, helping them to identify unhealthy factors and instill best practices that create healthy cultures and foster diversity.

While the issue is complex, Dr. Malcom is confident the outlook is positive and sees more potential for progress in the scientific community. “We have evolved in the way we think about diversity in science. Now I think we are at a point where we can begin to talk about diversity, equity, and inclusion as central for excellence in research,” she said. “We all have our biases, but the question is: what do you do in spite of them and how do you overcome them?”

Inside AJHG: A Chat with Elizabeth Wright

Posted By: Sara Cullinan, PhD, Deputy Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month we check in with Elizabeth Wright to discuss her paper ‘Practical and ethical considerations of using the results of personalized DNA ancestry tests with middle-school-aged learners’.

Elizabeth Wright, PhD
Elizabeth Wright (photo courtesy Dr. Wright)

AJHG: What prompted you to start working on this project?

Elizabeth: I could give you a long answer about being a former middle school science teacher and what drove me to get a PhD in Science Education, but simply put, I am committed to finding ways for each and every student to see themselves connected to science and each other, and supporting teachers in that work.

AJHG: What about this paper/project most excites you?

Elizabeth: I am equally thrilled and cautious about having adolescents use their own personal DNA to explore who they are genetically, genealogically/socioculturally, and intentionally. We are not all of one thing and none of another. We can use what we know about pieces of ourselves to imagine something new and amazing. We can reveal these pieces of ourselves to our families and friends and see how we are connected to each other and the grander tree of life.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Elizabeth: In the previous question I mentioned a bit about what thrills me. I am cautious because the privacy issues surrounding over-the-counter, direct-to-consumer DNA testing are monumental, and ever-shifting. It is both exciting and nerve-wrecking to ask, and watch, young scholars to embark on this intellectual journey. The engagement and electricity in the classroom when young scientists encounter themselves in new and unique ways keeps me going.

AJHG: What advice do you have for trainees/young scientists?

Elizabeth: I think the most important thing I would say is: you belong here. You belong in science. Your voice, your experiences, your viewpoint are all incredibly important. If you feel left out or unwelcome, create your own community and persevere because you are going to change things.

AJHG: And for fun, tell us something about your life outside of the lab.

Elizabeth: I’m a Red Sox season ticket holder and I love the game of baseball. I’ve been to baseball games in 27 different MLB parks, and 3 AAA baseball parks. Also, I love Orangetheory Fitness! Base-Push-All Out, that’s good advice.

Elizabeth Wright, PhD, is a postdoctoral fellow in the Jablonski laboratory at Pennsylvania State University.

Make the Case for Conference Attendance: Here’s How

Posted By: Ann Klinck, Communications & Marketing Assistant; and Amanda Olsen, Meetings Assistant, ASHG

Many institutions and organizations are on a yearly budget, which means now is the time to request funding for any educational and professional development opportunities you have in mind for 2019. If you’re attending the ASHG 2019 Annual Meeting, the best way to get funding is to submit your request early, appeal to your institution’s mission, and fulfill any promises you make during your appeal when you return.

Starting Early

With more professional development opportunities arising in the form of webinars, special-interest conferences, and service-learning, your department likely has a hard choice to make when deciding who and what to fund, even with an increased professional development budget. Many of these allocations are first come, first serve. Now is the time to do your research and put in those requests!

Figure out approximately how much you’ll need to attend the event including travel, registration, and hotels. Not every conference or meeting will have registration open in time for your request, but ASHG shows the benefit of early registration by sharing prices and price increase timelines well ahead of the ASHG Annual Meeting. Many organizations, including ASHG, share hotel rates ahead of time. Booking flights early doesn’t always get you the best savings, but using tools like the Kayak Travel Hacker Guide will help you know when to start booking and what kind of price you can anticipate.

Clearly indicate the financial savings of booking early and include all your research in your value of attending letter. Use our blog from last year to cut costs when traveling.

Appeal to the Mission

20190131_roitoolkit-imageThe Return on Investment (ROI) Toolkit helps you convey that while this meeting will benefit you, it will also benefit your institution since they are supporting your attendance.

  • Note which topics are being presented that directly correlate to your work.
  • State that the meeting isn’t just a learning opportunity but is also valuable for networking and can increase the possibility to collaborate.
  • Consider presenting your work, which would help get more visibility for your research and your institution.
  • Most importantly, explain that you’ll be ready to share all this new information upon your return. Sharing your findings with colleagues increases the value of attending to your institution by increasing the number of people who benefit from the cost.

See some other ways to get the most of a scientific meeting.


Fulfill Promises

Meetings can take a lot of energy, both mental and physical. Days full of new content can leave you burnt out and speechless when asked “what did you learn?” That’s why ASHG created several tools to help you keep track of it all. Track your participation on paper, or use our app! There are notes sections in each session listing where you can type about the session, and then email them to yourself later.

We’re looking forward to collaborating with you in Houston, so use the ROI Toolkit and get moving on those value of attending letters!

Voice Your Concerns about the U.S. Government Shutdown’s Impact on Science

Posted By: Staff

The American Society of Human Genetics (ASHG) deeply believes that ongoing federal government support is essential for the scientific enterprise in the United States. We affirm the important role of normal operations to keep scientific progress moving forward.

20190124_capitolAlthough – fortunately – the National Institutes of Health (NIH) is operational during the partial U.S. government shutdown, other science-based agencies that support and facilitate ASHG members’ work and that of their colleagues are not. Notably, the National Science Foundation (NSF) is affected.

ASHG is proud to stand with the Federation of American Societies for Experimental Biology (FASEB) in letting Congress know how the shutdown is affecting science. Please use FASEB’s Legislative Action Center to contact your members of Congress about how the shutdown is impeding progress and reaffirm the importance of science agencies in advancing research.

 

Inside AJHG: A Chat with Alan Beggs

Posted By: Sara Cullinan, PhD, Deputy Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month we check in with Alan Beggs to discuss his paper ‘Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project’.

Several members of the BabySeq research team
Several members of the BabySeq research team, including (L to R) Katie Dunn, Casie Genetti, Ingrid Holm, Alan Beggs, Robert Green, and Pankaj Agrawal. (courtesy of Dr. Beggs)

AJHG: What prompted you to start working on this project? 

Alan: It is well established that genomic sequencing of individuals with a likely genetic disease has clear and recognized benefits that easily outweigh the risks and costs.  However, we are just beginning to appreciate the potential benefits and costs of prospectively sequencing healthy individuals. There is a lot of hope around the prospects for disease prediction, presymptomatic diagnosis, carrier detection, pharmacogenomics and other potential benefits of genomic sequencing, and an equal amount of concern around the risks of misuse of genetic information, misinterpretation of probabilistic results or negative personal impacts such as anxiety, increased family stress or loss of trust that such information might engender.

The NIH Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) program was conceived to explore the implications, challenges, and opportunities of genomic sequencing in the newborn period. Together with our colleagues here in Boston, and in Houston, Robert Green and I designed the BabySeq Project to experimentally measure the medical, behavioral, and economic outcomes by prospectively sequencing both healthy and sick newborns and then following the consequences of returning results to them, their physicians and to their medical records.

AJHG: What about this paper/project most excites you? 

Alan: Although thousands of both healthy and sick individuals have undergone genomic sequencing by now, BabySeq represents one of the first prospective, randomized controlled trials of sequencing for which disease detection was not a primary goal. By enrolling newborn participants regardless of their medical status we can achieve one of the less biased comparisons within a human population. Although our sample size is modest, we were surprised to find in the sequencing arm that 9.4% of the infants, including ten of 127 healthy newborns, harbored what we considered to be a monogenic disease risk alleles, in other words, genetic variants that are predicted to cause disease using current best practices for determining disease-gene association and variant interpretation. Such a high rate of predicted genetic morbidity suggests either that we currently underestimate genetic contributions to common disorders such as heart disease or cancer, or that our variant predictions of pathogenicity or assumed disease gene penetrances are over estimated.

I think the randomized controlled aspect of this study is something else that excites me. It is providing an important opportunity for Amy McGuire and her team at Baylor to more rigorously assess the psychological and social implications of having genomic information at an early age. Funding permitting, we aim to follow the BabySeq families in both the sequenced and control arms well beyond the one-year follow-up surveys currently in progress, and I expect that we will be able to provide some hard data to address some of the concerns surrounding potential negative implications of learning genetic information.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Alan: This is a difficult question to answer!  Of course, just about everyone who has interviewed me has asked whether I think sequencing of newborns will become standard of care. The first point I make is that, for the foreseeable future at least, we absolutely do not view this as a replacement for traditional newborn screening, which targets a carefully chosen group of treatable diseases using tests with well-established and high degrees of sensitivity and specificity.

There is no question in my mind that rapid genomic testing is indicated for newborns with undiagnosed medical conditions that may have a genetic basis, and it is gratifying to see that geneticists and neonatologists are rapidly adopting this, and that third part payers are finally starting to come around and reimburse for this. Although I’m confident the data will eventually show that the risks of newborn sequencing in healthy infants are acceptably low, the benefits will be harder to establish and are likely to be uneven: most newborns will not have immediately actionable findings, but identification of carrier states will occasionally lead to identification of couples at-risk for future pregnancies, and presymptomatic diagnosis of even untreatable conditions such as Duchene muscular dystrophy, will help some families avoid having affected children in the future. Occasionally, and with increasing frequency, an early diagnostic finding will lead to potentially life saving interventions or surveillance, as in the case of the families we identified with variants for hereditary cancer syndromes. As our understanding of disease-gene associations and variant interpretation improves, more and more children will stand to benefit from such information.

The newborn period is a hectic and disruptive time for new families, so I think genomic sequencing for healthy babies is more likely to be eventually offered in late infancy or early childhood, much like many vaccinations are offered today. Before this happens though, it will be up to us, the professional genetics community, to engage with our colleagues, legislators, third party payers, and most importantly the public, in a discussion to determine when the broader societal benefits justify the risk and the costs, and to ensure that genetic information is protected to avoid misuse and discrimination.

AJHG: What advice do you have for trainees/young scientists?

Alan: Follow your heart and pursue the questions that excite you, but be mentally flexible and look for opportunities to work with outstanding scientists who will appreciate and support your efforts. Early in my postdoctoral career, my advisor passed away suddenly and I was faced with a career-altering dilemma. I was fortunate to find an outstanding new mentor in Dr. Lou Kunkel, and my career path shifted abruptly to focus on neuromuscular disease, and eventually genetics and genomics of rare diseases.  Science, and society, are constantly evolving, so put aside your preconceived notions of what “should” or “will” happen, and follow the data and opportunities wherever they lead.

AJHG: And for fun, tell us something about your life outside of the lab.

Alan: I like learning about new things, so I tend to be a generalist with broad interests who enjoys tinkering and trying different things. I’m not an expert in any one area, but I’ve dabbled in woodworking, I like repairing broken things, from dishwashers to lawnmowers (YouTube is great for that!), and I’ve got a killer fish tank at home. I also love to be outdoors, and I’m just as happy raking leaves, cleaning my gutters, or shoveling snow in the middle of the night as I am kayaking or skiing.

A longtime ASHG member, Alan Beggs, PhD, is Director of The Manton Center for Orphan Disease Research at Boston Children’s Hospital and the Sir Edwin and Lady Manton Professor of Pediatrics at Harvard Medical School. 

ASHG-AJHG Webinar Summary: Therapeutic Developments in Genetics

Posted By: Staff

Therapeutic developments in genetics is quickly becoming a key area of interest for many in the field. Earlier this month, ASHG co-hosted a webinar with The American Journal of Human Genetics (AJHG) to discuss the process from discovering a genetic mutation for a disease, to developing a therapy. AJHG Editor Bruce Korf moderated, and was joined by two expert panelists Susan Slaugenhaupt, PhD of Massachusetts General Hospital and Harvard Medical School, and Matt Alexander, PhD of the University of Alabama at Birmingham and Children’s of Alabama.

Susan presented her work on developing a drug to modify RNA splicing in a rare disease known as Familial Dysautonomia (FD), which has been a 25-year effort. FD currently has no cure, or pharmaceutical treatment, and the only method of care is symptomatic treatment.

FD has a plethora of symptoms including impaired smell, failing vision, imbalance, organ dysfunction and several others. Susan explained that while this disease affects few globally, “A significant number of human mutations have been shown to alter RNA splicing, and RNA splicing is something that we can target.” She continued to elaborate that “As we think about developing drugs for RNA splicing, they may prove useful in a whole variety of diseases.”

While the science of the disease is pivotal to discovery, Susan reminds us that the “how to,” for the process is just as important. Below is a timeline showing when her laboratory received the National Institutes of Health (NIH) funding, and how they advanced the translational research project from that point (picture below).

NIH funding chart webinar
Timeline provided by Dr. Slaugenhaupt

Going through the timeline, Susan explained that her team discovered kinetin (6-furfurylaminopurine), a plant growth factor, caused a change in RNA splicing as the amount of kinetin was increased. As Susan’s team continued, they eventually found that while kinetin was not potent enough to act as a drug, it was a good starting point to find new splice modulator compounds. For a complete explanation of Susan’s research and what this discovery meant for FD research, please watch the full webinar.

Matt presented on the advances in genetic based drugs for Duchenne Muscular Dystrophy (DMD), and the difficulties in working with neuromuscular diseases.

The DMD mutation is an X-linked recessive inheritance, and thus largely affects males. Approximately 1 in 5,000 live male births are affected. DMD causes the muscles in the shoulder, upper arm, hips, and legs to deteriorate. Patients present signs typically between ages 3-5 and are often in wheelchairs by age 13. Matt added that, “A really underappreciated aspect of the disorder is that approximately 20-25% of DMD boys are diagnosed with autism spectrum disorder.”

There are several therapeutic approaches to aid DMD patients currently being investigated, however Matt specifically discussed exon skipping drugs, CRISPR, and current gene therapy trials. These efforts, are essentially done in hopes of seeing a partially functional dystrophin protein, which would lessen the severity of the disease. The full webinar further discusses models used to test these approaches, and their possible side effects.

Matt additionally noted that when dealing with gene-based therapies for DMD it’s pivotal to have “really good biomarkers and quantification tools to indicate the amount of dystrophin protein being produced,” to accurately show the effectiveness of gene-based therapies.

The webinar concluded with a Q&A portion with questions from the audience. To stay up to date on our next webinar with AJHG, follow us on social @GeneticsSociety.

Inside AJHG: A Chat with Vijay Sankaran

Posted By: Sarah Ratzel, PhD, Science Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author(s) of a recently published paper. This month, we check in with Vijay Sankaran to discuss his paper, “The Genetic Landscape of Diamond-Blackfan Anemia.”

AJHG: What caused you to start working on this project?

Vijay Sankaran, MD, PhD
Vijay Sankaran (photo courtesy Dr. Sankaran)

Vijay: When exome sequencing was starting to be done routinely around 2009, we reasoned that Diamond-Blackfan anemia would be an ideal disease to study using this approach. At the time, only a few ribosomal protein mutations had been described in this disease and we thought that such sequencing approaches could help us better define the pathogenesis of this disorder. We did identify some non-ribosomal protein mutations through focused efforts (e.g. GATA1), but we kept sequencing more individuals to more comprehensively define the genetic landscape of this blood disorder. This paper describes the comprehensive analysis of the full cohort of individuals we studied.

AJHG: What about this paper most excites you?

Vijay: There are three things that excite me most about this work. First, this paper is really the culmination of several years of incredibly hard work by a number of talented trainees in our group, as well as fabulous colleagues. It is great to see their work put together and presented so nicely. Second, I think this analysis can serve as a model for other systematic studies in cohorts of individuals with a range of rare diseases. It provides a framework for thinking about how to perform comprehensive analyses in rare disease cohorts, while also illustrating major challenges in trying to define genetic etiologies. Third, I think the work nicely outlines the future directions we hope to take to better define the genetic causes for the remaining ~20% of cases and understand the basis for the variable penetrance observed.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Vijay: We have examined a rather large cohort of ~470 individuals with a rare disease that occurs in ~1 in 200,000 live births. This cohort took many years to put together and required extensive international collaborations. Despite the considerable size of this cohort (for a rare disease), we still could not define the potential genetic etiology for a number of individuals in the cohort. Our burden analyses nicely show how we are sufficiently powered to detect mutations in the exome that explain > 5% of cases in the cohort. Given all of this, our findings emphasize the need for larger analyses of such rare diseases. This can only happen through collaboration. Different investigators need to be willing to come together to maximize our ability to identify additional genetic causes for rare diseases. While many in the human genetics community appreciate the importance of such efforts, I still find that many colleagues in my clinical field and others are hesitant to share data. As a physician, I realize that doing so is critical for all patients and individuals affected by rare diseases.

AJHGWhat advice do you have for trainees/young scientists?

Vijay: Probably the most useful advice I can offer is that any trainee should pursue problems and work in environment where they can most enjoy their work. I have been incredibly fortunate to work in environments, both as a trainee and faculty member, where I have been given the freedom to pursue problems I am passionate about. As a result, I have also tried to create an environment in the lab that can enable trainees to do the same, which I believe is very important.

AJHG: And for fun, tell us something about your life outside of the lab.

Vijay: One of the things I enjoy outside of lab is exploring the fantastic restaurants in Boston and listening to jazz music (particularly when it is live).

Vijay Sankaran, MD, PhD, Assistant Professor of Pediatrics at Harvard Medical School and an Attending Physician in Hematology/Oncology at Boston Children’s Hospital and the Dana-Farber Cancer Institute. He has been an ASHG member since 2016.