Development of germline editing continues in the shadows. It’s time to replace prohibition with responsible regulation.
The idea of changing a baby’s DNA before birth stands as one of modern science’s most controversial frontiers – framed by futurists as humanity’s next evolutionary step and by opponents as modern eugenics. The time has come to break the decade-long limbo surrounding germline editing that began with CRISPR’s advent. Rather than maintaining blanket prohibitions that drive research underground, we must develop a regulatory framework to evaluate the risks and medical benefits of genetic modifications that can be passed to future generations.
My perspective comes from direct experience in this field working to develop CRISPR treatments in the more traditional sense. I have spent the last 10 years broadening the applications of CRISPR, starting in Jennifer Doudna’s Lab at UC Berkeley and continuing at Mammoth Biosciences, a company I co-founded back in 2018. While my background gives me insight into the technology’s potential, I recognize that no individual should determine what constitutes safe and ethical use of germline editing.
Note: Given the controversy of this topic I feel obligated to say these views are mine and don’t reflect the perspectives of Mammoth or the people I work with.
History Germline Editing
Germline editing was not always a taboo topic to discuss as it is today. In the early years of CRISPR, germline editing was often discussed as an eventuality of the technological breakthrough, with headlines about the future of designer babies overshadowing the therapeutic applications that are now a reality. In 2015, prominent academics called for a temporary pause in pursuing germline editing to allow an appropriate ethical and regulatory framework to be put in place. Shortly after, the US Congress barred the FDA from reviewing any therapies that cause heritable genetic changes through a congressional rider. This call and the US congressional rider was found to be inconsequential when, in 2018, a scientist in China (Jiankui He/JK) edited two babies without any regulatory oversight or ethical discussion.
The edits made had none of the safety assessment that is standard for any gene editing program and only edited a fraction of the embryo, highlighting the researcher’s, extremely limited knowledge and capabilities in how to safely and efficiently conduct gene editing. The experiment opened the eyes of scientists and the public to how accessible CRISPR had made germline editing, with a largely unknown lab being able to do it with reagents that could be received through the mail. More recently, JK has also become active on X and continues to defend and look for funders for his haphazard use of embryo editing even after going to prison.
In response to the unregulated germline editing in 2018, a different group called for another moratorium in 2019 despite the ineffectiveness of the first call in 2015. This article, published in Nature, suggested five years as the appropriate time to wait before reviewing the topic.
Now, five years after this call, the topic remains in a state of indefinite pause in the US. Anecdotally, many scientists in the field fear discussing the subject publicly, stifling a necessary debate on the merits and risks of heritable editing. Meanwhile, the ability to safely and precisely edit the human genome has advanced, with the first CRISPR therapy approval last year. Editing has progressed to precision writing in sequences, modifying epigenetics, and changing single DNA bases along with well established techniques to understand off target editing.
Outside the US, individual countries are relaxing their restrictions on germline editing including most recently South Africa. In short the field continues to move forward outside of the mainstream discussion.
Correcting Before Birth vs. After Birth
Germline editing and editing after birth aren’t competing approaches, but complementary tools in our therapeutic arsenal. Each has unique advantages that make them suited for different scenarios, and a modern healthcare system will likely employ both to maximize patient benefit.
Heritability
- Current Approach: When we treat genetic diseases in adults using somatic editing we modify only specific body tissues, the disease-causing mutation remains in reproductive cells. Children often still inherit the condition.
- Germline Advantage: Correcting mutations in embryos fixes the problem in all cells, including reproductive ones, preventing transmission to future generations. The flip side of this is if you make a change that is negative, that also propagates raising the bar for the burden of proof that the change is safe to make and increasing the importance of having a careful regulatory review of genetic edits in place of having this be unregulated.
Prevention vs Treatment
A potential advantage of germline editing lies in the timing of correction and the ability to edit all cells in the body. The adage, “An ounce of prevention is worth a pound of cure,” is especially relevant for genetic diseases, where developmental damage is often irreversible
- Current Approach: Adult treatments typically correct only a fraction of affected cells and at a time after the disease has progressed.
- Germline Advantage: Germline editing ensures all cells carry the correction. In Friedreich’s Ataxia for example, which affects multiple tissues, current treatments struggle to reach all affected areas. However, this advantage comes with an important caveat: in diseases where genetics don’t guarantee disorder development, early intervention might prove unnecessary for some individuals.
Cost and Accessibility
Gene therapy headlines are often dominated by the cost of treatment, which can soar into the millions of dollars. Although these therapies can be much more cost-effective compared to existing care (which can be hundreds of thousands annually for the patients entire life) they are not feasible for developing countries where much of genetic disease resides.
- Current Approach: Adult gene therapies often cost millions per patient. The first approved CRISPR therapy costs $2.2 million per patient. These costs depend heavily on the mode of delivery and development costs and could come down in the future.
- Germline Editing: Integration with IVF could cost thousands rather than millions. Genetic screening and editing during IVF might add $2,000-5,000 to standard procedure costs. If done in situ the cost could be even lower. When amortized across the generations this number becomes vanishingly small.
Safety Considerations
While safety concerns are paramount for any genetic intervention, germline editing offers unique advantages for comprehensive safety verification:
- Unlike adult treatments where effects must be extrapolated from limited samples, embryonic editing allows direct verification of genetic changes
- Whole genome sequencing can thoroughly evaluate unintended modifications since all cells will carry the same modifications.
- Pre-implantation genetic testing provides an additional layer of safety verification
Germline editing vs Embryo Selection
Critics argue that embryo selection through IVF eliminates the need for germline editing. This oversimplifies both the practical and ethical realities. IVF often yields few viable embryos, leaving many couples without the luxury of choice. Furthermore, embryo selection faces many of the same ethical considerations as germline editing, yet is widely accepted in clinical practice.
More critically, there are scenarios where embryo selection is simply not viable. Consider sickle cell disease in Nigeria, where 1-2% of the population has the condition and 20-30% are carriers. This means tens of thousands of couples where both parents have sickle cell disease – for them, embryo selection cannot prevent passing the condition to their children. Germline editing could offer these families a path to having children without the disease.
A Practical Path Forward
Previous efforts to establish a framework for germline editing have failed. Why, and how can we proceed differently? For one, the topic has been approached from the angle of if we should allow germline editing. This gives the discussion a false sense of control over the situation. Instead, we need to accept that this has happened and will continue to happen. Our goal should be to put the appropriate guardrails in place to encourage it to happen safely and ethically in the open instead of behind closed doors and likely in countries seen as adversaries by the United States. We must stop the pejorative labeling of accusing anyone who brings up the topic as a proponent of eugenics.
The path forward requires three key steps:
- Select a first disease with limited options for existing treatments
- Establish a group with resources and expertise to conduct the appropriate safety and efficacy studies
- Submit for regulatory review (outside the US if no change to the congressional rider) and allow regulatory systems to do what they are designed for – evaluate an intervention based on its benefit and risks
Unfortunately, germline editing has emerged when reproductive policies are more polarized than ever in the United States. While the current congressional rider could be revised in the next budget cycle, other countries may lead the way. Nations like Italy and Finland, which have some exceptions for germline editing for therapeutic purposes, could pioneer responsible development.
This work demands resources for preclinical studies and regulatory engagement. A coordinated group – whether company or nonprofit – must assemble resources to establish safe protocols. By conducting the first regulated use within an established framework, we can set precedent for evaluating germline editing like any other therapeutic intervention, based on safety and medical benefit.
In closing, the appropriateness of germline editing depends highly on the specific needs and targets. However, dismissing this technology outright leaves us with no opportunity to evaluate its medical utility. By accepting that this technology exists and is accessible, we open the door to a future where regulated prevention of genetic disorders is within reach. As Louis Brandeis noted, “Sunlight is said to be the best of disinfectants.”