Broadies,

The start of the new academic year is always a good time to reflect on where we’ve been, and more importantly, where we’re headed.

This year feels different because the federal government’s approach to scientific research has changed so dramatically. As an institution, we don’t take positions on political matters. But the fact is that reduced federal funding for biomedical research negatively impacts our ability to make discoveries to help patients. The difficult staffing changes and other cost reductions we made over the summer were a direct response to the changing federal climate and will position us well for the future.

During any financial downturn, the temptation is always to retreat and ride things out — but it would be a mistake to lower our research ambitions. Broad will continue to aim high, and we’ll work creatively and collaboratively to overcome the challenges ahead. I remain incredibly optimistic about Broad’s unique position in the research ecosystem, and our ability to accelerate research progress throughout the country and the world. Our research is stunningly innovative and impactful, and our administrators are incomparable in their support of science.

The first chapter of the Broad Institute (our first two decades) was about laying foundations — technical foundations enabling genomic data generation at unprecedented scale, and community foundations enabling multidisciplinary and multi-institutional teams to solve problems that couldn’t be solved by individual labs. This first chapter led to the discovery of genetic variants associated with disease, and revolutions in single cell biology and gene editing technologies that have rippled across the world.

The next chapter of the Broad must be about turning those foundations into therapeutic benefit for patients, and doing so in Broad’s unique way — combining scale, interdisciplinarity, and a deep commitment to doing together what we cannot accomplish alone.

Of course it’s difficult to boil down all of our science into just a couple of ideas. But I see two major components to Broad’s next chapter: 1) converting genetic variation associated with disease into mechanistic insights to inform therapeutics, and 2) driving a revolution in “programmable therapeutics” whereby genetic medicines become truly scalable for common and rare diseases.

Turning genetic associations into therapeutic insights will require that we learn how to make mechanistic studies scalable. Undoubtedly, the hundreds or thousands of risk variants associated with any particular disease don’t represent hundreds or thousands of disease mechanisms; our task must be to discover the biological story that those variants are collectively telling.

This was not yet possible during Broad’s first chapter — but Broadies, collaborators, and colleagues around the world changed the game. We can now use gene editing to systematically install any sequence change into any cell, and determine the consequence of such perturbations using molecular readouts and imaging. This makes the prospects of functional biology at scale feasible for the first time. The work will not be for the faint of heart — it will require massive perturbational profiling (on the scale of billions of cells), extending analyses to the tissue and organismal level, and using AI to turn data into insights.

And, we’ll need to bring these same scalable approaches to bear on understanding the non-genetic component of disease, discovering the molecular mechanisms by which life experiences impact health and disease.

Broad’s second area of focus is on making programmable therapeutics a reality. While small molecule therapeutics will continue to be important, nucleic acid-derived therapeutics represent an enormous opportunity for patient impact, with potential to become truly scalable in a way that small molecules are not.

We now have proof of concept that therapeutic gene editing can be safe and effective. It is now time to carve a path toward scalable gene editing — for rare diseases (where commercial incentives are limited), and for common diseases and even cancer. This will require solving remaining technical challenges (e.g., limitations of gene delivery) and addressing regulatory hurdles, working collaboratively with government agencies, hospitals, and company partners. Broad is ideally suited to play this role.

Beyond gene editing, programmable therapeutics also involves systematic approaches to mRNA therapeutics, next generation antibody design, and even AI-designed therapeutic proteins that don’t exist in nature. Such ambitious goals are unlikely to be accomplished by individual labs. But Broad has a tradition of working as an interdisciplinary team across institutions to make the impossible possible, and as a result, catalyzing progress around the world.

As we start this new academic year, I hope you share my excitement about the scientific opportunities ahead, and our ability to use science to benefit patients. The federal government’s shifting approach to research will no doubt make it more challenging to achieve our ambitious goals, at least in the short run. But out of such challenges come new opportunities — for partnership with companies, other academic institutions, and even the government itself. In the end, scientific progress and the public’s desire for good health will triumph.

Our next Community Update will be Monday, September 22 at 10:45 am in the Merkin auditorium and streamed online. We’ll share more about our scientific vision and how we’re organizing to accomplish it, share what we know about the federal situation, and also answer your questions. Until then, I remain inspired by your resilience, and grateful for your feedback and creativity as we write Broad’s next chapter together.

Todd