ASHG recently responded to a select number of questions in a Request for Information (RFI) from the White House Office of Science and Technology Policy (OSTP) on the National Biotechnology and Biomanufacturing Initiative. OSTP released this RFI to seek public input on how advances in biotechnology and biomanufacturing can help support a strong bioeconomy. The insights provided by human genetics and genomics are fundamental for the health biotechnology ecosystem and are critical components of the bioeconomy. ASHG’s response includes actionable comments on genetics and genomics technology goals, community engagement models for diverse research participation, equitable workforce development, creating a responsible open data sharing ecosystem, and the responsible stewardship of human genomic data. By responding to this RFI, ASHG remains committed to integrating human genetics and genomics across all facets of research, medicine, and society to the benefit of all people.
What specific bold goals for health (biotechnology and biomanufacturing to achieve medical breakthroughs, improve health outcomes, or reduce the overall burden of disease) can be achieved through advances in biotechnology and biomanufacturing in the short-term (5 years) and long-term (20 years)?
The American Society of Human Genetics (ASHG) is a society of genetics professional members, with the mission to advance human genetics and genomics in science, health and society through excellence in research, education, and advocacy. Our approximately 8,000 members are researchers, medical geneticists, genetic counselors, and others who share the common goal of encouraging people everywhere to realize the full potential and benefits of human genetics and genomics, including areas relevant to the National Biotechnology and Biomanufacturing Initiative. The insights provided by human genetics and genomics has enabled discoveries in practically every life science field, building from the fundamental understanding of DNA – the basis of life on which our form and function depends. Today, human genetic and genomic technologies, such as sequencing and advanced genomic analytics, are combined with several relevant biotechnology advancements to propel biopharmaceuticals, diagnostics, and other medical technologies that leverage genomic information.
A recent ASHG report identified eight major goals of genomics that have incredible future potential to advance health. All of them rely on, and will have a major impact for, biotechnology. These goals, including their technical challenges, are greatly expanded upon in ASHG’s commissioned report on the functional and economic impacts of human genetics and genomics, and in summary they are:
- Goal 1 – Minable Big Data (Discovery Science): Analyzing sequencing data from large and diverse populations to provide deep insights into disease biology and identify characteristics associated with health
- Goal 2 – Identifying Predisposition to Diseases and Disorders: Genetic and genomic testing to identify carrier status, and identify predisposition for genetic disease via prenatal, newborn and adult screening
- Goal 3 – Diagnosing Diseases and Disorders: Using biomarkers and gene signatures to diagnose the presence of diseases or disorders that are associated with specific genes or gene products
- Goal 4 – Rational Drug Development: Using genetic information and gene associated biomarkers to inform molecular targeting in drug design
- Goal 5 – Pharmacogenomics (Personalized Medicine): Using sequencing data to enable the prescription of drugs best suited to the patient’s genotype (increasing efficacy and reducing adverse effects)
- Goal 6 – Gene Editing and Gene Therapy: Modifying the genes associated with a disease or disorder to treat or cure a disease
- Goal 7 – Human Microbe Interaction: Examining the human genome’s impact upon hosted microbial populations, and microbe impacts upon the human genome and gene expression
- Goal 8 – Environmental Genomics and Metagenomics: Examining the impact of human interventions with the environment on the human genome, gene regulation, mutation, and disease etiology
It should also be noted that genomics impacts many other areas beyond health including agriculture, industrial biotechnology, environmental and ecological services, paternity testing, evolutionary biology and anthropology, and forensic science.
What research and development (R&D) is needed to achieve these bold goals, with a focus on cross-cutting or innovative advances? How would the Government support this R&D, including through existing Federal programs, creation of new areas of R&D, and/or development of new mechanisms?
Improving Capacity to Integrate and Analyze Huge Volumes of Genetic and Genomic Data. Rapidly decreasing sequencing costs have enabled the production of a massive total amount of genomic data on the level of exabytes that can be analyzed. Critical to digesting these massive datasets are computational data sciences and analytics, which can use machine learning and artificial intelligence processes to process genomic data at unprecedented pace. As exceptional as these advancements have been, researchers are limited in their progress if they do not have access to these data. Different forms of data, including genetic, genomic, environmental, and health, each provide important insights alone but promise far greater knowledge when examined together – presenting a unique challenge of analyzing large heterogenous data types compiled from numerous sources. Advanced data analytic techniques offer the ability to link heterogenous datatypes, repositories, and processes with each other and ensure an interoperable data ecosystem.
Translating Human Genetics and Genomics Research and Innovation to Clinical Outcomes. Genetics and genomic data contribute in many ways to health and clinical outcomes. For example, the association between a person’s genome and health outcomes has led to the development and application of polygenic scores (PGS), often called polygenic risk scores (PRS) in the context of disease. This statistical tool has shown promise for studying the biology of complex traits and for evaluating individual disease risks in clinical settings. Critical to implementing these scores in clinical settings, per ASHG’s recent Guidance on the topic, are developing diverse research cohorts across multiple dimensions, fostering robustness in the development, application, and interpretation of PGS, and improving the communication of PGS results, including limitations, and their implications to broad audiences. Human genetics and genomics research drives clinical outcomes in many forms, including its ability to identify predisposition to diseases and disorders; diagnose disease, rare diseases, and disorders; inform rational drug development; potentiate targeted therapeutics through precision medicine; and contribute to the development of safe gene therapeutics. Though each of these goals encompasses numerous intrinsic research and development barriers needing to be addressed, they are generally united by further research and development focusing on the identification of biomarkers useful for clinical practice, understanding how to integrate genetic information into existing U.S. medical systems, expanding reference genomes reflecting the rich diversity of the world population, and understanding better the off-target effects of potential genome therapies.
How else can the Government engage with and incentivize the private sector and other organizations to achieve these goals?
Recognizing the Complex Network of Federal Agencies and Institutions, Industries, Academic, and Nonprofit Actors that Fund Genetic and Genomics Research. It is important to recognize the wide diversity of federal sources that fund fundamental genomic research, detailed with enumeration in our commissioned report. The report revealed that nearly half of all NIH research funding was connected in some form to human genetics and genomics technology, giving an incredibly broad portfolio of communities that ultimately fund genetics and genomics research. Although most funding comes from NIH, the Department of Veterans Affairs (VA) Office of Research and Development, National Science Foundation, and other agencies in the U.S. Department of Health & Human Services have also greatly contributed to federal research funding for human genetics and genomics. Alongside countless private, nonprofit, and academic actors, it is important to recognize the complex landscape of entities that contribute to the research funding landscape that should be part of incentivization discussions.
Public engagement and acceptance are of critical importance for successful implementation of biotechnology solutions for societal challenges. How might social, behavioral, and economic sciences contribute to understanding possible paths to success and any hurdles? What public engagement and participatory models have shown promise for increasing trust and understanding of biotechnology?
Encourage the use and expansion of federal community engagement programs, such as the NIH Community Engagement Alliance (CEAL) with NHGRI in consultation with NHLBI and NIMHD, to build diversity in research participation. ASHG is committed to sustain efforts to ensure that people everywhere can realize the benefits of human genetics and genomics. Per our recently published Guidance, we believe that community engagement is an effective approach that can be used across the research lifecycle to address health inequities and increase the representation of underrepresented populations in genetics and genomics research. We especially applaud efforts to expand successful community engagement programs, such as the NIH CEAL initiative Against COVID-19, to establish and coordinate a community engagement program that will support efforts to increase the participation of individuals historically underrepresented and hesitant to participate in human genetics and genomics research. As the original CEAL initiative was implemented to promote community engagement and outreach efforts to diverse communities hit hardest by the COVID-19 pandemic, expanded models can use community engagement and educational outreach activities to coordinate with local organizations to increase diverse research participation and build meaningful, long-term, and trustworthy partnerships with historically underserved communities. The successes and lessons learned from these programs can be applied to other areas of biomedical research.
Create resources for educators to gain cultural awareness and competency relating to genetics and society. ASHG denounces the misuse of genetics to feed racist ideologies, and from ASHG’s Perspective, the Society encourages the research community to be clear about genetic knowledge related to ancestry and genomic diversity. Teachers are often asked to navigate conversations and questions about genetics intersecting with the social environment and culture. Open resources and webinars, such as those created by the ASHG Public Education & Awareness Committee, can create valuable long shelf-life assets to aid educators in these endeavors.
Importance of ELSI research for human genetics and genomics in healthcare and society. It is important to recognize the researchers that contribute to the understanding of ethical, legal, and social issues affecting and affected by genetics and genomics technology. These researchers cover many topics pertinent for the responsible use of genomics in healthcare and society, including privacy and fairness in the use and interpretation of genetic information; clinical integration of genetic technologies; informed consent and ethical, legal, and ethnocultural issues encompassed by genetics research; equitable access to genetics and genomics technology; and ongoing education efforts of multiple audiences.
What data types and sources, to include genomic and multiomic information, are most critical to drive advances in health, climate, energy, food, agriculture, and biomanufacturing, as well as other bioeconomy-related R&D? What data gaps currently exist?
Striving for Equity though Diverse Participation in Genetics and Genomics Research and Data. Genetic science can advance health equity through the deliberate, meaningful inclusion and participation of individuals from diverse groups in human genetics and genomics research. The inclusion of populations representing diverse ancestries helps us gain a fuller understanding of the genetics of health and disease, knowledge which can be used to develop more accurate diagnostic tests and more effective treatments that benefit all Americans. Diverse participation in research is essential if we are to realize the full promise of human genetics and genomics research and the equitable application of genetic discoveries in healthcare and society. The Society commends NIH’s efforts to advance diverse participation in research, particularly the All of Us Research Program. Significantly, in 2022, this program released a database of health information and whole-genome sequences from almost 100,000 individuals, half of whom are from historically underrepresented racial or ethnic backgrounds.
Advancing Human Microbiome, Metagenomics, and Environmental Genomics Efforts. Beyond the human genome are countless individual genomes belonging to other biological and environmental systems. There are dimensions of how the human genome interacts with each of these entities with implications for human health. Large-scale sequencing programs and efforts, such as Genomic Encyclopedia of Bacteria and Archaea (GEBA) project and the Human Microbiome Project (HMP), act to provide a rich resource for scientists to mine in metagenomic studies – yet many of these projects remain under-resourced. Further building these valuable reference repositories and connecting them with clinical isolates can dramatically accelerate progress in these studies.
How can the Federal Government, in partnership with private, academic, and non-profit sectors, support a data ecosystem to drive breakthroughs for the U.S. bioeconomy? This may include technologies, software, and policies needed for data to remain high-quality, interoperable, accessible, secure, and understandable across multiple stakeholder groups.
Support broad data sharing with considerations for responsible stewardship and privacy protections of human genomic data. The sharing of human genome research data is indispensable for advancing human genetics and genomics research and medicine, and the willingness of researchers to share their data has been a hallmark of the human genomics field for decades. This has been reflected in a broad number of examples of both national and international efforts including the Human Genome Project, the Database on Genotypes and Phenotypes (dbGaP), cBioPortal for Cancer Genomics, the H3Africa consortium, All of Us, and the International HundredK+ Cohorts Consortium. ASHG supports policies and systems that facilitate research while ensuring that research participants’ genomic information remains confidential with protections for privacy in place, including the Genetic Information Nondiscrimination Act (GINA), 21st Century Cures Act, Common Rule (U.S. Federal Policy for the Protection of Human Subjects (45 CFR 46)), NIH Genomic Data Sharing Policy, Affordable Care Act, and the HIPAA Privacy Rule. The human genetics and genomics community has been a leader in ensuring that human genomic data are protected. This community is committed to responsible stewardship and to the responsibility that comes with research and use of new knowledge. The research community is proactive in addressing privacy risks or breaches, assessing how new technological advances could identify individuals from genomic information, and helping to lead the development or revision of professional practices to protect confidentiality. To maximize the public’s investment in the NIH and the contributions of the public who participate in science, it is imperative that we continue to proactively facilitate and encourage responsible data sharing to fuel scientific advances.
How can the U.S. strengthen and expand the biotechnology and biomanufacturing workforce to meet the needs of industry today and in the future? What role can government play at the local, state, and/or Federal level?
Leverage broad partnerships to develop a mentoring ecosystem and community for trainees from underrepresented backgrounds. ASHG, in partnership with NHGRI, Biogen, GSK, Roche, and Merck & Co., Inc, hosts a program called the Human Genetics Scholars Initiative. This program is centered on selecting a diverse cohort of high-potential early career individuals for professional success by establishing powerful mentor-mentee relationships, building robust skillsets, and giving these individuals sustained attention to issues in their research institutions and training programs. These actions focus on developing and maintaining a community of researchers committed to diversity, equity, and inclusion to bolster an innovative, scientific ecosystem. This partnership between ASHG, federal government, and industry can be an example for future programs.
What strategies and program models have shown promise for successfully diversifying access to biomanufacturing and biotechnology jobs—including those involving Historically Black Colleges and Universities, Tribal Colleges and Universities, and other Minority Serving Institutions? What factors have stymied progress in broadening participation in this workforce?
Identification of factors that have stymied broadening participation in this workforce. ASHG has recently released the Human Genetics & Genomics Workforce Survey Report, which takes an in-depth look at the field’s workforce demographics, including race, ethnicity, or ancestry; gender identity; sexual orientation; age; disability status; and disadvantaged background. The report’s findings verify the pace of progress has been slow in addressing the lack of diversity in the human genomics and genetics sector and reveals insights that underscore the challenges organizations must address to build a more diverse workforce. Discussion amongst focus groups emphasized the need for data transparency, metrics, and accountability on demographic data on diversity for employees and students. Additionally, these conversations identified the need for tangible signs that organizations have an inclusive culture, including visible representation and access to informational mentoring relationships and advancement opportunities.
What quantitative indicators, economic or otherwise, are currently used to measure the contributions of the U.S. bioeconomy? Are there new indicators that should be developed?
Leveraging partnerships to understand the economic and functional impact of research. With support from industry partners, ASHG commissioned a comprehensive report on the economic and health impacts of genetics and genomics with contributions from ASHG leaders and other experts in the field. Importantly, the report discussed two macro classes of genetics and genomics impact: economic impacts (examining the impact of human genetics and genomics on the U.S. economy) and the functional (application) impact domains in which genetics and genomics are affecting human health and the clinical practice of medicine.
What risks are associated with international biotechnology development and use, and how can the U.S. Government work with allies and partners to mitigate these risks?
Prioritizing both medical progress and national security goals through collaborative partnerships. The successful response of the international research community to the COVID-19 pandemic highlights the value of international collaboration for advancing scientific progress. ASHG supports policies that promote genetic and genomic data sharing to advance research and health care with strong protections in place for genetic information. To serve the American people, it is vital that the nation prioritize both robust medical progress and national security goals and ensure they co-exist and advance as two top priorities. Imposing undue burdens and restrictions on U.S. researchers through roadblocks to data sharing, which is already heavily regulated, could decrease the global competitiveness of U.S. geneticists, and potentially harm responsible and vital global scientific collaboration that advances genomics research for the benefit of all. Losing our important advantage of shared data could challenge our leadership in genomics and thus weaken the U.S. Before requiring any major new national security frameworks on NIH-funded human genetics and genomics research, Congress should first commission a study that brings together leading scientists and national security experts as equals. The commission would determine and document what national threats exist, if any, given the statutory and regulatory frameworks in place protecting the privacy of human genetic information, and provide guidance to HHS and NIH on the interface of scientific and national security goals. If this study were to conclude that there is a body of evidence establishing a clear threat to national security, scientists should then be empowered to work alongside—not subject to—the national security community to determine how to mitigate the threat while ensuring scientific progress.
Establishing the importance of universal ethical standards in science. Successful international collaboration relies on scientists’ common agreement on, and consistent adherence to, foundational ethical standards for public participation in research. Long-standing ethical principles for genetics research help respect and protect research participants, and they are especially important for preventing harm to marginalized or vulnerable populations. Recent reports allege that several genetic studies conducted in China may not have secured individuals’ consent for their participation freely and without coercion. Instances of unethical treatment of participants in human genetics research are neither new nor specific to China. ASHG will continue to advocate for the robust enforcement of international ethical practices in science, including the principle of informed consent for research participants. We must all continue to practice, teach, and demand ethical conduct of science through our professional capacities so that research participants’ rights are honored, and scientific advances benefit all people.