Sorry you asked? Mayo, Myriad, and the battles over patent-eligibility.

Genetic testing for inherited cancer risk changed dramatically when the US Supreme Court handed down unanimous rulings in Mayo v. Prometheus (2012) and Myriad v. Association for Molecular Pathology (2013). Those decisions struck down claims to methods based on 'laws of nature' (Mayo) and DNA molecules corresponding to sequences found in nature (Myriad). Senators Thom Tillis (R-NC) and Christopher Coons (D-DE) introduced legislation that would abrogate those decisions and specify narrow statutory exclusions to patent-eligibility in §101 of the US Patent Act. What would be the consequences of doing so? The Supreme Court decisions coincided with changes in how genetic tests were performed, reimbursed and regulated. Multi-gene sequencing supplanted oligo-gene testing as the cost of sequencing dropped 10,000-fold. Payers dramatically changed reimbursement practices. Food and Drug Administration regulation was proposed and remains in prospect. Databases for clinical interpretation made data freely available, augmenting a knowledge commons. The spectacular implosion of Theranos tempered investment in molecular diagnostics. These factors all complicate explanations of why venture capital funding for molecular diagnostics dropped relative to other sectors. Restoring patent-eligibility would put renewed pressure on other patent doctrines, such as obviousness, enablement and written description, that were not raised in the Supreme Court cases.

The Myriad Decision at 10.

A decade ago, the US Supreme Court decided Association for Molecular Pathology v. Myriad Genetics, Inc., concluding that isolated genes were not patentable subject matter. Beyond being a mere patent dispute, the case was a political and cultural phenomenon, viewed as a harbinger for the health of the biotechnology industry. With a decade of perspective, though, Myriad's impact seems much narrower. The law surrounding patentable subject matter-while greatly transformed-only centered on Myriad in small part. The case had only a modest impact on patenting practices both in and outside the United States. And persistent efforts to legislatively overturn the decision have not borne fruit. The significance of Myriad thus remains, even a decade later, hidden by larger developments in science and law that have occurred since the case was decided. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 25 is August 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Big advocacy, little recognition: the hidden work of Black patients in precision medicine.

As cost-effective next-generation genome sequencing rapidly develops, calls for greater inclusion of Black people in genomic research, policy, and practice are necessary for effective translation of genomic science into precision population health and medicine. Employing a community-based participatory mixed methods research design, we developed a semi-structured survey that was disseminated to three cancer advocacy organizations. Of the 81 survey respondents 49 (60%) self-identified as Black, and 26 (32%) indicated a prior breast cancer diagnosis. Black participants' expressed concerns about genetic testing were evenly distributed between concerns that could be addressed through genetic counseling (24%) and concerns about subsequent use of their genetic data (27%). Patient advocates contributed to contextualization of respondent concerns in terms of community experiences. Although genetic counseling services and policies governing genomic data use are not always accessible to many Black communities, advocates on our research team provided a bridge to discussion of the intersection between respondent concerns and the roles advocates play in filling gaps in access to genetic counseling and data governance. Concerns expressed by Black patients underscore a shared need among all patients for access to education, inclusion in research, and assurances regarding the use and handling of genetic data. Black cancer patients have joined in patient-led efforts to overcome systemic inequities in cancer care to improve their health outcomes through representation. Often their efforts are overshadowed by a relentless burden of continued health disparities. Future research should support their hidden work as a means to reduce barriers and improve representation in genomic databases.

Payer reimbursement practices and incentives for improving interpretation of germline genetic testing.

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for private payers and Medicare illustrate opportunities and challenges for data sharing to close knowledge gaps and improve clinical utility. Policy options include making data sharing (i) a condition of payment, and (ii) a metric of laboratory quality in payment contracts, yielding preferred coverage or enhanced reimbursement. Mandating data sharing sufficient to verify interpretations and resolve discordance among labs under Medicare and federal health programs is an option for the US Congress. Such policies can reduce the current waste of valuable data needed for precision oncology and improved patient outcomes, enabling a learning health system.

Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi.

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.

Big Advocacy, Little Recognition: The Hidden Work of Black Patients in Precision Medicine.

Public health genomics prioritizes effective and ethical translation of genomic science into population health precision medicine. With the rapid development of cost-effective, next-generation genome sequencing, calls are growing for greater inclusion of Black people in genomic research, policy, and practice. Genetic testing is often the first step in precision medicine. This study explores racial differences in patient concerns about genetic testing for hereditary breast cancer. Employing a community-based participatory mixed methods research design, we developed a semi-structured survey that was shared broadly. There were 81 survey respondents, of which, forty-nine (60%) self-identified as Black, twenty-six (32%) indicated they had a history of a breast cancer diagnosis, or had received BRCA genetic testing. Black participants who expressed concerns about genetic testing were fairly equally distributed between concerns that could be addressed with genetic counseling (24%) and concerns about the subsequent use of their genetic data (27%). The concerns expressed by the participants in our study underscore a need for transparent disclosures and assurances regarding the use and handling of genetic data. These findings should be viewed in context with patient-led efforts to overcome systemic inequities in cancer care, as Black cancer patients have joined forces with advocates and researchers to develop protective health data initiatives and to improve their representation in genomic datasets. Future research should prioritize the information needs and concerns of Black cancer patients. Interventions should be developed to support their hidden work as a means to reduce barriers and improve representation in precision medicine.

Fresh takes on five health data sharing domains: Quality, privacy, equity, incentives, and sustainability.

As entities around the world invest in repositories and other infrastructure to facilitate health data sharing, scalable solutions to data sharing challenges are needed. We conducted semi-structured interviews with 24 experts to explore views on potential issues and policy options related to health data sharing. In this Perspective, we describe and contextualize unconventional insights shared by our interviewees relevant to issues in five domains: data quality, privacy, equity, incentives, and sustainability. These insights question a focus on granular quality metrics for gatekeeping; challenge enthusiasm for maximalist risk disclosure practices; call attention to power dynamics that potentially compromise the patient's voice; encourage faith in the sharing proclivities of new generations of scientists; and endorse accounting for personal disposition in the selection of long-term partners. We consider the merits of each insight with the broad goal of encouraging creative thinking to address data sharing challenges.

The Bayh-Dole Act at 40: Accomplishments, Challenges, and Possible Reforms.

More than 40 years have passed since the enactment of the Patent and Trademark Amendment (Bayh-Dole) Act, which authorized institutions to patent inventions arising from federally funded research. Although some experts have heralded the Bayh-Dole Act as ushering in a new era of technological advances, others have been less sanguine about its impact. In recent years, the high price of prescription drugs and the patenting of COVID-19 therapeutics and vaccines developed with substantial federal government support have rekindled the debate over whether companies should receive more restricted rights to products originating with government funding. This article traces the history leading to the enactment of the Bayh-Dole Act and critically assesses its strengths and weaknesses as well as unresolved questions concerning its scope. Based on this analysis, the authors propose reforms to better align the Bayh-Dole Act with public values and health outcomes, including clarifying government-use rights, making it easier to invoke march-in rights for failure to meet health and safety needs, increasing transparency in how patents are licensed, and testing different approaches to foster the development and application of inventions.

The Human Pangenome Project: a global resource to map genomic diversity.

The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene-disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.

U.S. Adult Perspectives on Facial Images, DNA, and Other Biometrics.

Applications of biometrics in various societal contexts have been increasing in the United States, and policy debates about potential restrictions and expansions for specific biometrics (such as facial recognition and DNA identification) have been intensifying. Empirical data about public perspectives on different types of biometrics can inform these debates. We surveyed 4048 adults to explore perspectives regarding experience and comfort with six types of biometrics; comfort providing biometrics in distinct scenarios; trust in social actors to use two types of biometrics (facial images and DNA) responsibly; acceptability of facial images in eight scenarios; and perceived effectiveness of facial images for five tasks. Respondents were generally comfortable with biometrics. Trust in social actors to use biometrics responsibly appeared to be context specific rather than dependent on biometric type. Contrary to expectations given mounting attention to dataveillance concerns, we did not find sociodemographic factors to influence perspectives on biometrics in obvious ways. These findings underscore a need for qualitative approaches to understand the contextual factors that trigger strong opinions of comfort with and acceptability of biometrics in different settings, by different actors, and for different purposes and to identify the informational needs relevant to the development of appropriate policies and oversight.

Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

Balancing openness with Indigenous data sovereignty: An opportunity to leave no one behind in the journey to sequence all of life.

The field of genomics has benefited greatly from its "openness" approach to data sharing. However, with the increasing volume of sequence information being created and stored and the growing number of international genomics efforts, the equity of openness is under question. The United Nations Convention of Biodiversity aims to develop and adopt a standard policy on access and benefit-sharing for sequence information across signatory parties. This standardization will have profound implications on genomics research, requiring a new definition of open data sharing. The redefinition of openness is not unwarranted, as its limitations have unintentionally introduced barriers of engagement to some, including Indigenous Peoples. This commentary provides an insight into the key challenges of openness faced by the researchers who aspire to protect and conserve global biodiversity, including Indigenous flora and fauna, and presents immediate, practical solutions that, if implemented, will equip the genomics community with both the diversity and inclusivity required to respectfully protect global biodiversity.

Breathing fresh air into the debate: Ventilators and the United States' intellectual property problem.

In 2006, the U.S. federal government launched a project to create a cheap, easily produced, and easy to use ventilator that could be stored for long periods of time for pandemic response. Despite successful funding and contracts with two separate medical device companies, not a single ventilator had been added to the stockpile by 2020. The company currently under federal contract for these ventilators is selling its product to private parties, rather than supplying it to the federal government. In the current crisis, government has instead turned to the Defense Production Act to supply ventilators. Inaccessibility of medical equipment is a detriment to Americans' health, particularly during a public health emergency like COVID-19. This persists despite the central role of the federal government in the funding of healthcare innovation. We place the shortage of ventilators in context of the ongoing debate about the federal government's intellectual property powers, as well as the legal recourses available, then discuss why this situation is a strong argument for expanding compulsory licensing powers as a component of federal policy.

A survey of U.S. public perspectives on facial recognition technology and facial imaging data practices in health and research contexts.

Facial imaging and facial recognition technologies, now common in our daily lives, also are increasingly incorporated into health care processes, enabling touch-free appointment check-in, matching patients accurately, and assisting with the diagnosis of certain medical conditions. The use, sharing, and storage of facial data is expected to expand in coming years, yet little is documented about the perspectives of patients and participants regarding these uses. We developed a pair of surveys to gather public perspectives on uses of facial images and facial recognition technologies in healthcare and in health-related research in the United States. We used Qualtrics Panels to collect responses from general public respondents using two complementary and overlapping survey instruments; one focused on six types of biometrics (including facial images and DNA) and their uses in a wide range of societal contexts (including healthcare and research) and the other focused on facial imaging, facial recognition technology, and related data practices in health and research contexts specifically. We collected responses from a diverse group of 4,048 adults in the United States (2,038 and 2,010, from each survey respectively). A majority of respondents (55.5%) indicated they were equally worried about the privacy of medical records, DNA, and facial images collected for precision health research. A vignette was used to gauge willingness to participate in a hypothetical precision health study, with respondents split as willing to (39.6%), unwilling to (30.1%), and unsure about (30.3%) participating. Nearly one-quarter of respondents (24.8%) reported they would prefer to opt out of the DNA component of a study, and 22.0% reported they would prefer to opt out of both the DNA and facial imaging component of the study. Few indicated willingness to pay a fee to opt-out of the collection of their research data. Finally, respondents were offered options for ideal governance design of their data, as "open science"; "gated science"; and "closed science." No option elicited a majority response. Our findings indicate that while a majority of research participants might be comfortable with facial images and facial recognition technologies in healthcare and health-related research, a significant fraction expressed concern for the privacy of their own face-based data, similar to the privacy concerns of DNA data and medical records. A nuanced approach to uses of face-based data in healthcare and health-related research is needed, taking into consideration storage protection plans and the contexts of use.

Lessons from Biomedical Innovation during World War II.

The United States developed penicillin and vaccines during World War II. The partnership of government, industry, and academe was crucial. In an essay, Vannevar Bush credited that partnership with the technological achievements that led to winning the war. The policies used to address the Covid-19 pandemic closely resemble how penicillin was developed, and similarly produced spectacular success in the form of RNA-based vaccines. But will today's politics of hyperpartisan vitriol and credit-mongering that pit industry against government and academe prevent carrying that success into the postpandemic era?

Governing Heritable Human Genome Editing: A Textual History and a Proposal for the Future.

Heritable human genome editing (HHGE) has become a topic of intense public interest, especially since 2015. In the early 1980s, a related topic-human genetic engineering-was the subject of sustained public discussion. There was particular concern about germline genetic intervention. During the 1980s debate, an advisory committee to the Director of the National Institutes of Health (NIH)-the Recombinant DNA Advisory Committee (RAC)-agreed to provide initial public review of proposals for deliberate introduction of DNA into human beings. In 1984 and 1985, the RAC developed guidelines for research involving DNA transfer into patients. The committee also commented on the possibility of deliberately altering the human germline. We track the textual changes over time in the RAC's response to the possibility of germline genetic intervention in humans. In 2019, the NIH RAC was abolished. New techniques for genome editing, including CRISPR-based techniques, make both somatic and germline alterations much more feasible. These novel capabilities have again raised questions about oversight. We propose the creation of a new structure for the public oversight of proposals to perform HHGE. In parallel with a technical review by a regulatory agency, such proposals should also be publicly evaluated by a presidentially appointed Bioethics Advisory Commission.

Challenges to Building a Gene Variant Commons to Assess Hereditary Cancer Risk: Results of a Modified Policy Delphi Panel Deliberation.

Understanding the clinical significance of variants associated with hereditary cancer risk requires access to a pooled data resource or network of resources-a "cancer gene variant commons"-incorporating representative, well-characterized genetic data, metadata, and, for some purposes, pathways to case-level data. Several initiatives have invested significant resources into collecting and sharing cancer gene variant data, but further progress hinges on identifying and addressing unresolved policy issues. This commentary provides insights from a modified policy Delphi process involving experts from a range of stakeholder groups involved in the data-sharing ecosystem. In particular, we describe policy issues and options generated by Delphi participants in five domains critical to the development of an effective cancer gene variant commons: incentives, financial sustainability, privacy and security, equity, and data quality. Our intention is to stimulate wider discussion and lay a foundation for further work evaluating policy options more in-depth and mapping them to those who have the power to bring about change. Addressing issues in these five domains will contribute to a cancer gene variant commons that supports better care for at-risk and affected patients, empowers patient communities, and advances research on hereditary cancers.