Ten years ago, the idea of editing human genomes to prevent disease or enhance traits might have seemed like the stuff of science fiction. Today, not only is it possible—it’s a rapidly advancing field. A recent paper in Nature, “Heritable Polygenic Editing: The Next Frontier in Genomic Medicine,” explores this possibility in detail. It lays out how, within the next few decades, heritable polygenic editing (HPE) could become a transformative tool in medicine. But as I’ve seen firsthand, particularly during my time at Colossal, this timeline might be even shorter than the experts predict.
The Science Has Advanced, and It’s Accelerating
Polygenic editing in this article focuses on changing multiple genetic variants to reduce the risk of complex diseases like Alzheimer’s, coronary artery disease, and type 2 diabetes. Unlike single-gene editing, which targets rare genetic conditions, polygenic editing addresses diseases influenced by hundreds—or even thousands—of genetic factors. While editing a single variant associated with Alzheimer’s might only marginally reduce risk, editing ten or more variants simultaneously could bring lifetime prevalence down from 5% to under 0.6%, according to the Nature study.
This kind of large-scale editing may sound futuristic, but it’s not far off. At Colossal, we worked on multiplex editing—the ability to make hundreds of precise genetic changes simultaneously. Tools like CRISPR are being refined to handle this scale, and while they’re not quite there yet, the rapid progress in precision and efficiency is undeniable. What once seemed technically impossible is now more of a matter of engineering than a conceptual breakthrough. I even had an entire team dedicated to understanding the genotype-to-phenotype relationship and what edits we could make to change an elephant into a mammoth.
Remind me another day to write an article on where an elephant ends and a mammoth begins.
From Controversy to Capability
The idea of heritable editing took center stage in 2018, when He Jiankui, a Chinese scientist, announced the birth of two genetically edited babies. His goal was to make the children immune to HIV by editing a single gene, but the move sparked global outrage, ending up with a three-year prison sentence. The experiment was condemned as unethical and premature, and Jiankui faced significant legal and professional consequences. The uproar was a clear message: the technology was not ready for clinical use, and we lacked the governance needed to manage its potential risks.
Fast forward to today, and the landscape looks very different. The same controversies that stymied Jiankui’s work catalyzed a wave of research and innovation aimed at making genome editing safer, more precise, and scalable. Scientists and companies are no longer asking if we can make large-scale genetic edits but how to do it responsibly and effectively. The focus has shifted from isolated experiments to building the infrastructure needed for routine, high-volume editing. Techniques to minimize off-target effects, ensure accurate editing, and optimize delivery methods are advancing at breakneck speed.
HPE Could Change Healthcare Forever
The implications of heritable polygenic editing are staggering. The Nature paper highlights how a small number of genetic edits could drastically reduce disease risk in edited genomes. For example, editing ten genetic loci associated with coronary artery disease could lower an individual’s lifetime risk from 6% to just 0.1%. Similar reductions could be achieved for type 2 diabetes, Alzheimer’s, and schizophrenia.
This is not theoretical; the foundational technologies are being developed today. CRISPR-based methods are already being used in clinical trials for somatic (non-heritable) gene editing, treating diseases like sickle cell anemia. Scaling these methods to heritable edits will require additional safeguards and testing, but the technical groundwork is being laid.
At Colossal, we saw firsthand how quickly multiplex editing is evolving. The tools to edit multiple loci simultaneously are improving to the point where the idea of editing hundreds of genetic variants in a single procedure is no longer science fiction. The challenge is no longer one of “if,” but of refining the process to ensure precision and safety. They even recently announced they achieved 300+ genetic edits in a single cell in their Thylacine project.
This progress is, in fact, so closely related to the HPE Nature article that it’s part of what inspired me to start dabbling in writing sci-fi as well. More on that later.
The Challenges Ahead
Of course, significant hurdles remain. Even as the science progresses, there are practical and ethical challenges to address:
Safety and Precision: Large-scale editing increases the risk of off-target effects. Even minor unintended edits can have significant consequences, particularly if they are heritable. Scientists are racing to perfect methods that minimize these risks.
Cost and Accessibility: Technologies like HPE are likely to be expensive in their early stages, raising concerns about equity. If only the wealthy can afford to edit disease risk out of their genomes, this could exacerbate existing health disparities.
Public Perception and Regulation: The controversy surrounding Jiankui’s experiment highlights how critical public trust and strong regulatory frameworks are to the success of genome editing. Clear guidelines and transparent communication will be essential to avoid another public backlash.
Ethical Boundaries: Should we limit genome editing to disease prevention, or allow enhancements like increased intelligence or athletic ability? How do we define the line between medical necessity and personal preference? Will society ever allow these types of choices?
Why This Matters Now
For all the challenges, it’s clear that HPE is not decades away—it’s within reach. The convergence of biotechnology, data science, and engineering has accelerated progress to a pace that few anticipated. And while we still need to resolve critical ethical and regulatory questions, the science is moving forward regardless.
The implications for healthcare are profound. HPE could redefine preventive medicine, allowing us to address the root causes of disease rather than treating symptoms. It could free millions of people from the burden of chronic illness and dramatically reduce healthcare costs. But it also raises difficult questions about how to balance innovation with equity and governance.
What This Means for Us
As someone who has spent years working at the intersection of biotechnology and advanced technologies, I see HPE as both an incredible breakthrough and a daunting responsibility. The choices we make now—about how to develop, regulate, and deploy these technologies—will shape not just the future of medicine, but the future of humanity.
These connections are the crux of why I started The Connected Ideas Project. TCIP is built on the idea that breakthroughs like this don’t happen in isolation. They’re part of a broader narrative of how technology and society evolve together. Heritable polygenic editing is one of the most impactful stories of our time, and it’s a story we need to tell right—because it’s unfolding much faster than most people realize.
Let’s stay ahead of it. Let’s shape it. Let’s keep pushing boundaries—and stay connected.
Cheers,
-Titus
The podcast audio was AI-generated using Google’s NotebookLM
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