Balancing Innovation and Ethics: A CRISPR Approach to Patent Law

In August 2017, a team of scientists at the Oregon Health & Science University (OHSU) successfully edited the DNA of a human embryo using CRISPR-Cas9, repairing a genetic defect that causes a debilitating disease. [1] The excitement in the room was palpable as they witnessed a historic moment that could change the future of medicine. However, as they celebrated this scientific breakthrough, ethical questions loomed large. What if this powerful tool were used to create so-called “designer babies” or to enhance physical or cognitive traits? Who would regulate such profound capabilities? 

CRISPR-Cas9 allows precise editing of an organism’s DNA by using a guide RNA—similar to a Global Positioning System (GPS) tracker—to direct the “Cas9” protein to a specific genetic location, allowing scientists to alter genetic material accurately. [2] However, the ethical implications of editing germlines—decisions that affect future generations without consent—raise complicated legal challenges. Such interventions infringe upon future individuals’ autonomy and rights, specifically their right to an unaltered genetic identity. Policymakers and legislators must decide whether future generations could assert legal standing to challenge the choices made on their behalf before their birth and existence. CRISPR-Cas9 poses risks like unintentional genetic mutations and the loss of genetic diversity, stressing the urgent need for a legal framework to address ethical concerns such as informed consent and equitable access to gene-editing medical technologies. International treaties and joint efforts between national regulatory bodies will be required to specify global ethical standards and prevent disparities in regulating germline editing across sovereign borders.

He Jiankui, a Chinese geneticist, caused global controversy in 2018 when he announced the birth of the world’s first gene-edited babies, Lulu and Nana. [3] Using CRISPR-Cas9 technology, he reconfigured the embryos’ genomes to confer resistance to the Human Immunodeficiency Virus (HIV) by targeting the CCR5 gene, the main gate HIV uses to break down the cellular integrity of human immune cells. [4] However, this risky medical procedure disregarded established regulatory oversight and ethical processes, exposing a vast chasm in international legal frameworks governing gene-editing technology. China’s vacuum state for stringent regulatory mechanisms underscores the need for universal standards to prevent such rogue scientific experimentation. This failure might have been avoided under the more rigorous regulatory structures in the United States or the European Union.

Given the birth of gene-edited babies in China, integrating CRISPR technology will require a dual regulatory approach: (1) establishing comprehensive legal and ethical frameworks governing human germline editing and (2) revising intellectual property laws to balance innovation with equitable access carefully. These adaptations allow for safe, ethical applications and facilitate continued innovation, benefiting patients and the global scientific community. 

Henry T. Greely, a prominent legal scholar and bioethicist, discusses the complex dynamics and potential pitfalls of patenting CRISPR-Cas9 technology. The “key patents being fought over” relate to CRISPR-Cas9. However, the author points out that “exciting publications have already seen the light of day about many other Cas proteins” and other “cutting” proteins. [5] Greely cautions that restrictive patents can stifle innovation and prompt researchers to find loopholes to avoid infringement, thus eventually circumventing the patented technology. High licensing fees could lead to a “classic death spiral” where high prices drive customers to seek cheaper alternatives, simply perpetuating the cycle. [6] This can reduce demand for the original technology and force prices even higher for the remaining users, further accelerating the shift to other viable alternatives. Balanced patent policies are necessary for accessibility and innovation while preventing high costs and market incongruity.

In Association for Molecular Pathology v. Myriad Genetics, Inc., the Supreme Court reviewed the patentability of naturally occurring DNA sequences, impacting the complex legal landscape for genetic technologies, including CRISPR. The case addressed the patent eligibility of naturally occurring DNA segments versus synthetically created DNA. The Court ruled in 2013 that naturally occurring DNA sequences, even when isolated, are not patentable because they are indubitably products of nature. However, cDNA, which is synthetically created and does not occur naturally, is patentable because it involves an innovative intervention in its creation. [7] By ruling that naturally occurring DNA sequences are not patentable, the Court reinforced the principle that discoveries of natural phenomena do not constitute human inventions. The decision demonstrates the need to incentivize technological advancement through patent protection to preserve the building blocks of nature available for scientific progress. Future genetic research and biotechnology regulations should focus on redefining intellectual property rights commensurate with technological progress to encourage innovation while maintaining access to essential scientific tools. Priority must be open access to knowledge, ethical considerations, and promoting collaboration between the public and private sectors. 

Vera L. Raposo, an Assistant Professor of Law and Technology at Núcleo de Objetivos para a Valorização Acadêmica (NOVA) School of Law, raises crucial ethical concerns about informed consent in germline editing, particularly the “lack of informed consent over changes to the genetic constitutions of persons who do not yet exist,” which she argues restricts their autonomy. [8] While Raposo suggests that parental consent for genetic intervention could be likened to parental consent for medical acts affecting an unborn child, this analogy remains insufficient in the context of germline editing. In medical decisions, parental consent is based on emergency or imminent medical needs. On the other hand, germline editing fundamentally alters the genetic identity of future generations who cannot express any form of consent. Legally, this raises questions about whether future generations should have a voice to challenge genetic alterations made before birth and how courts might review such legal claims. Existing frameworks surrounding parental consent are inadequate to manage the profound implications of modifying an unborn child’s genetic makeup. Legislators and the high courts should establish specific policies ensuring that any germline interventions are not only in the best interest of the unborn child but also carefully regulated to prevent irreversible harm to future generations yet unborn, thereby preserving their autonomy. Moreover, creating a legal mechanism for oversight—through bioethics committees—would offer a more effective way to safeguard the rights of future generations.

The CRISPR Patent Dispute (UC Berkeley vs. Broad Institute) is a high-profile case centered on the ownership of CRISPR-Cas9 technology. [9] UC Berkeley and the Broad Institute filed patents claiming the invention. UC Berkeley demonstrated using CRISPR-Cas9 in prokaryotic cells (lacking a nucleus) in 2012. Broad Institute applied the technology to eukaryotic cells (containing a true nucleus) and received expedited patent approval in 2014. [10] UC Berkeley argued that Broad Institute’s patents for CRISPR-Cas9 technology in eukaryotic cells hindered UC Berkeley’s prior work on prokaryotic cells. However, the U.S. Patent Trial and Appeal Board (PTAB) and the Federal Circuit Court ruled in favor of Broad, finding that using CRISPR-Cas9 in eukaryotic cells was distinct and “non-obvious.” [11] The court focused on the “non-obviousness” standard in patent law, noting that technical challenges, such as the complexity of eukaryotic genomes and RNA stability, would have discouraged researchers from foreseeing success in transferring CRISPR technology from prokaryotes to eukaryotes. Broad’s expert witnesses highlighted these barriers, which the court found to support the ruling of “non-obviousness.” [12]

UC Berkeley instead argued that simultaneous invention suggested “obviousness,” but the court ruled that it did not outweigh the technical challenges specified by the Board. [13] The court ultimately upheld the Board’s ruling of no interference between the patents, affirming Broad’s precedence in using CRISPR-Cas9 on eukaryotic cells. [14]

This ruling significantly impacts the biotech industry as companies pursue CRISPR-based therapies. This concentration of patent control could stifle innovation in the biotech industry. One solution is establishing licensing frameworks that encourage broader access and cooperation, ensuring that advancements in CRISPR technology benefit more innovators, researchers, and patients. The guidelines and policies specified by the European Union (EU) for Standard Essential Patents (SEPs) seek to enhance efficiency in the licensing process. These guidelines mandate the voluntary registration of SEPs and encourage conducting periodical “essentiality checks” to demonstrate whether a patent is integral to the EU laws that ensure fair access to key industry players. Moreover, the framework incorporates a non-binding process for determining Fair, Reasonable, and Non-Discriminatory (FRAND) licensing agreements, providing a mechanism to resolve potential disputes before litigation. Additionally, the framework offers advisory services and reduced fees tailored explicitly to small and medium enterprises (SMEs), enabling easy access to standard-essential technologies for research institutions and private enterprises. [15] This approach balances innovation incentives with fair entry into essential medical technologies to drive innovation.

The U.S. Food and Drug Administration (FDA) is critical in regulating gene therapies through its Center for Biologics Evaluation and Research (CBER). [16] The FDA’s authority, derived from the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act, allows it to oversee gene therapies through clinical trials and manufacturing procedures. [17] However, to extend its jurisdiction to CRISPR-Cas9 and human germline editing, Congress must draft and pass statutory amendments that address gene-editing technologies. These changes will empower the FDA to regulate germline interventions, enforce long-term safety monitoring, and establish guidelines for managing ethical concerns unique to gene editing. These same principles can be applied to CRISPR-Cas9 technology, particularly in human germline editing. By requiring preclinical testing, long-term monitoring, and public transparency for any CRISPR-related clinical applications, the FDA could minimize the ethical risks related to gene editing, including off-target effects and unintended genetic modifications. Expanding the FDA’s regulatory framework to include gene-editing procedures would facilitate innovation while safeguarding patients and future generations from irreversible genetic malformations.

As aforementioned, the U.S. patent system has already confronted significant legal questions about genetic technology, most notably in the 2013 case, Association for Molecular Pathology v. Myriad Genetics, Inc., where the Supreme Court ruled that naturally occurring DNA sequences could not be patented. [18] However, synthetic DNA (cDNA) was deemed patentable due to its artificial creation. [19] Similar principles could guide the handling of CRISPR-Cas9 patents while distinguishing between natural gene sequences and engineered genetic modifications. Moreover, the patent dispute between UC Berkeley and the Broad Institute over CRISPR patents underscores the need for clear guidelines on balancing intellectual property rights with broad access to this transformative technology. A revised patent policy would protect researchers’ and innovators’ interests and ensure that CRISPR technology remains accessible for medical research while preventing monopolization by a few dominant players in the biotech industry.

The ethical complexities of CRISPR-Cas9 demand changes to existing regulatory frameworks. The FDA is well-positioned to oversee gene-editing technologies. However, Congress must pass a statutory amendment and empower the FDA with specific jurisdiction over germline interventions, ensuring long-term safety and ethical oversight. Such legislation is paramount for managing risks such as genetic mutations and facilitating equitable access.

On the intellectual property front, legal precedents such as the Association for Molecular Pathology v. Myriad Genetics, Inc. could serve as a litmus test for regulating CRISPR-Cas9 patents. Still, additional clarity is required, hence the need for statutory amendments. The UC Berkeley-Broad Institute legal saga foreshadows significant challenges concerning the “non-obviousness” of genetic modifications. These lengthy legal battles could suppress innovation if narrow patent interpretations restrict broader applications of CRISPR technology. A balanced patent framework is crucial to protect intellectual property without limiting access to indispensable medical technologies. As CRISPR technology advances, legislators, policymakers, the high courts, and international bodies must cooperate on a comprehensive legal framework to balance ethical issues and foster innovation without unintended and irreversible societal consequences.

Edited by Andrew Chung

[1] Françoise Baylis, Altered Inheritance: CRISPR and the Ethics of Human Genome Editing (Cambridge, MA: Harvard University Press, 2019), 47.

[2] Henry T. Greely, CRISPR People: The Science and Ethics of Editing Humans (Cambridge, MA: The MIT Press, 2021), 37.

[3] Greely, CRISPR People, 38.

[4] Antonio Regalado, “The Creator of the CRISPR Babies Has Been Released from a Chinese Prison,” MIT Technology Review, April 10, 2022, https://www.technologyreview.com/2022/04/10/1048605/he-jiankui-crispr-babies-released-from-chinese-prison/.

[5] Greely, CRISPR People, 43.

[6] Greely, CRISPR People, 44.

[7] “Annual Review of Law and Technology,” Berkeley Technology Law Journal 29 (2014): 385.

[8] Vera Lúcia Raposo, “CRISPR-Cas9 and the Promise of a Better Future,” European Journal of Health Law 26 (2019): 308.

[9] Charlotte Lepic, “University of California v. Broad Institute: Court Affirms Broad’s Patent on Complex Cell Gene-Editing Tool,” Harvard Journal of Law & Technology Digest, October 10, 2018, https://jolt.law.harvard.edu/digest/university-of-california-v-broad-institute-court-affirms-broads-patent-on-complex-cell-gene-editing-tool.

[10] Lepic, University of California v. Broad Institute.

[11] Lepic, University of California v. Broad Institute.

[12] Lepic, University of California v. Broad Institute.

[13] Lepic, University of California v. Broad Institute.

[14] Lepic, University of California v. Broad Institute.

[15] European Commission, “Standard Essential Patents,” April 27, 2023, https://single-market-economy.ec.europa.eu/industry/strategy/intellectual-property/patent-protection-eu/standard-essential-patents_en.

[16] U.S. Food & Drug Administration, “Cellular & Gene Therapy Products,” accessed June 27, 2023, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products.

[17] U.S. Food & Drug Administration, “Cellular & Gene Therapy Products.”

[18] Regalado, “The Creator of the CRISPR Babies.”

[19] Regalado, “The Creator of the CRISPR Babies.”