Tech titans lean into gene editing of embryos | The Dip Podcast

Key Concepts

• Gene Editing: The process of altering the DNA within cells using technologies like CRISPR.
• Somatic Gene Editing: Gene editing performed on cells in a person's body to treat existing diseases.
• Germline Gene Editing (Embryo Editing): Gene editing performed on human embryos, where changes are made at the point of fertilization and are heritable by future generations.
• CRISPR: A gene-editing technology that allows for precise modifications to DNA.
• Pre-implantation Genetic Diagnosis (PGD): A technique used with IVF to test embryos for genetic conditions before implantation.
• Eugenics: The practice of improving the human population by controlled breeding to increase the occurrence of desirable heritable characteristics.
• Ethics Dumping: The practice of conducting ethically or legally questionable research or activities in countries with less stringent regulations.
• Polygienic Embryo Screening: Genetic testing of embryos to assess risks for diseases and select for traits like height and intelligence.

Gene Editing and the Prospect of Designer Babies

The recent investment by Sam Altman and Brian Armstrong into a startup named Preventive, focused on editing genes in human embryos to prevent genetic diseases, has ignited a debate about the future of human reproduction. This development raises significant ethical, legal, and scientific concerns, prompting questions about whether it represents a humanitarian breakthrough or a return to eugenics under the guise of disease prevention.

Understanding Gene Editing Technologies

Gene editing refers to the modification of DNA within cells, primarily utilizing technologies like CRISPR. It's crucial to distinguish between two main types:

• Somatic Gene Editing: This involves altering DNA in a person's existing body cells to treat diseases. Breakthroughs in this area are already being seen in therapies for conditions like sickle cell disease.
• Germline Gene Editing (Embryo Editing): This is a more profound application where DNA changes are made to human embryos at the earliest stages of development, typically around fertilization. The intention is for these edited genes to be replicated in every cell of the developing embryo, resulting in a genetically modified child. Crucially, these changes would also be present in the individual's reproductive cells (sperm or eggs), meaning they would be passed down to all future generations. This heritable aspect is what distinguishes it from somatic gene editing and introduces a new set of concerns.

Implications of Germline Gene Editing

The ability to make heritable changes to the human genome through embryo editing carries significant implications:

• Heritability and Future Generations: Unlike somatic gene editing, changes made to embryos are permanent and will be inherited by offspring and subsequent generations. This raises concerns about unintended consequences and the long-term impact on the human gene pool.
• Safety and Accuracy: CRISPR, while powerful, is not always perfectly accurate. It can introduce unintended changes elsewhere in the genome ("off-target edits") or only affect some cells within the embryo ("mosaicism"). The long-term health effects of such alterations are largely unknown.
• Ethical and Societal Concerns: Beyond safety, germline gene editing raises profound ethical questions about altering the human germline, the potential for introducing societal inequalities, and the very definition of what it means to be human.

Concerns Regarding Startups and Regulation

The involvement of startups like Preventive, with their profit-driven motives, in such a sensitive area is a significant concern for experts like Katie Hassan, Executive Director of the Center for Genetics and Society.

• Lack of Regulatory Oversight: Conducting human experimentation, which embryo editing essentially is, within a startup environment with minimal regulatory oversight is highly concerning. Startups are driven by commercialization and investor returns, which may not align with a cautious and ethical approach to germline gene editing.
• Commercialization vs. Ethics: The pursuit of profit can overshadow the ethical considerations inherent in altering future generations. The potential for introducing inequalities, where certain children might be perceived as "improved" due to genetic modifications, is a major worry.

Addressing Concerns About Genetic Diseases

While acknowledging the desire to prevent genetic diseases, experts point to existing and alternative solutions:

• Diversity of Genetic Diseases: Not all genetic diseases are equally severe, and many individuals with genetic conditions live fulfilling lives.
• Somatic Gene Therapies: Significant progress is being made in somatic gene therapies that can treat genetic diseases in affected individuals.
• Pre-implantation Genetic Diagnosis (PGD): This technique, used in conjunction with IVF, allows parents to test embryos for specific genetic conditions and select unaffected ones for implantation.
• Egg or Sperm Donation: For parents concerned about passing on genetic conditions, using donor eggs or sperm offers a way to avoid transmission without altering the germline.
• Germline Editing's Unique Offering: The primary unique offering of germline gene editing is the ability to ensure a child is genetically related to both parents while also being free from a specific genetic condition. However, other methods exist to achieve disease prevention without this specific genetic relatedness.

The Challenge of Legal Guardrails and Enhancement

The idea of implementing legal guardrails to permit disease editing while prohibiting trait enhancement faces significant challenges:

• Existing Prohibitions: Over 70 countries, including the United States, already have legal prohibitions against creating genetically modified children through germline gene editing.
• Difficulty in Defining Lines: Drawing a clear line between therapeutic editing for severe diseases and enhancement is incredibly difficult. The definition of "disease" can be fluid, and the line between treating a predisposition and enhancing a trait can blur.
• "Off-Label" Use: In regulatory systems like the US, once a technology is approved by the FDA, physicians can often prescribe it for other indications ("off-label use"), making strict limitations challenging to enforce.
• The Slippery Slope of Polygienic Embryo Screening: The rapid shift in the market for polygienic embryo screening, from solely disease prevention to openly offering selection for traits like intelligence and height, serves as a cautionary example of how quickly the focus can shift from therapy to enhancement.

The Risk of "Genetic Tourism" and the Need for Global Action

The existence of varying regulations across countries raises the specter of "genetic tourism," where individuals might travel to jurisdictions with laxer rules to undergo germline gene editing.

• Undermining National Laws: This practice would undermine the laws and ethical stances of countries that prohibit germline gene editing, creating a global regulatory patchwork.
• Ethics Dumping: This phenomenon is sometimes referred to as "ethics dumping," where ethically or legally unacceptable practices are moved to countries with fewer restrictions.
• Need for International Moratorium: To address this, a coordinated international response, such as a global moratorium or ban on embryo gene editing, is considered necessary.
• Evidence of International Agreement: Research indicates a high degree of existing international agreement on prohibiting heritable genome editing, with over 70 countries having relevant prohibitions in place. No country explicitly permits it.

The Ethical Question of Equal Access

Even if germline gene editing were made universally accessible and affordable, it would not resolve the ethical concerns for many:

• Unrealistic Scenario: Achieving truly equal access to such advanced and potentially expensive technologies is considered unrealistic, especially in countries with existing healthcare disparities.
• Acceptance of Genetic Superiority: The fundamental ethical issue remains the societal acceptance of the idea that certain children are genetically superior to others. This concept, even if not factually true, can be deeply harmful and echoes the history of eugenics. The concern is not just about the rich having "super babies," but about the normalization of a hierarchy based on genetic makeup.

In conclusion, while the technology for gene editing is advancing rapidly, the application of germline gene editing to human embryos presents profound ethical, safety, and societal challenges. The potential for unintended consequences, the difficulty in drawing lines between therapy and enhancement, and the risk of exacerbating social inequalities necessitate a cautious and globally coordinated approach, prioritizing ethical considerations over rapid commercialization.