Congratulations to Doris Duke Foundation grantees Daniel E. Bauer (2013 and 2015), Stuart H. Orkin (2013 and 2015) and David Altshuler (2006) for the federal Food and Drug Administration’s historic approval of Casgevy—the first CRISPR-based cure for sickle cell disease approved for use in patients.
Drs. Bauer and Orkin, of Boston Children’s Hospital and Harvard Medical School, along with their colleagues researched and identified a core genetic mechanism in sickle cell disease that could be therapeutically targeted. Dr. Altshuler, a geneticist, is the chief scientific officer at Vertex Pharmaceuticals, which co-developed the now commercially-approved therapy with CRISPR Therapeutics.
Sickle cell disease, a genetic disorder that impairs the proper formation of red blood cells, affects about 100,000 people in the United States and millions around the world. In this country, the disease disproportionately burdens Black Americans.
The condition is terribly debilitating. Patients experience frequent pain, require intensive and expensive lifetime therapies, and almost invariably careen toward a painful, early death, one often due to manifold vascular and organ failures.
As clinical researchers are well aware, despite the disease first being described as early as the 1950s, progress to understand the disease’s mechanisms and translate those insights into viable therapies has been slow and plodding. And most of that progress has focused on alleviating the disease’s symptoms rather than curing the underlying condition itself.
Much of this marginalization has been ascribed to racism in the form of less urgency to address a disease primarily affecting Black Americans. Surely the story of sickle cell disease is one chapter in the dark history of a medical system that is inextricably bound up with the historical and persistent forces of racial discrimination in America.
But researchers also recognize that part of the challenge has been the lack of biomedical technology that can effectively respond to the complex nature of this disorder.
In her will, Doris Duke cited by name sickle cell disease as an example of the kinds of diseases she wanted her philanthropic legacy to help tackle. While it was only listed as an illustration, we have always taken seriously her specific awareness of this disease and its terrible and unjust toll in our quarter-century effort to support early-career talent in clinical science.
This led us in 2008 to develop our Innovations in Clinical Research Awards program to try to change the trajectory of sickle cell research. Our hypothesis was that attracting talent into this disease area could accelerate the development of transformative knowledge and increase incentives for promising researchers to devote their considerable talents to this neglected condition. Ultimately, we invested $17.1 million in 35 distinct research projects between 2009 and 2015. Many of the researchers supported through these grants continue to blaze new trails in understanding and addressing this disease.
In 2016, the emergence of gene-editing tools like CRISPR led us and many others to believe that we finally had the tools to move from care to cure. This led us to develop the Sickle Cell Disease/Advancing Cures program in 2017, which funded 19 research projects through $18.8 million and was focused on how to harness new technology like CRISPR to achieve breakthrough treatments.
Philanthropic capital is risk capital. Through its independence, philanthropic capital can take political, financial or technical risks that other kinds of capital—and especially public expenditure—cannot. When philanthropy works well, our actions can inspire the application of capital at a far larger scale by de-risking the learning cost associated with better understanding the nature of a problem and in assessing the feasibility and potential of various solutions.
Thanks to the work of the researchers in whom we invested and the far-sighted application of philanthropic investment by many others, the tens of millions of philanthropic dollars devoted to changing the trajectory of sickle cell have since resulted in follow on investments many times these original contributions.
Since 2008, the National Institutes of Health—which is the largest single funder of biomedical research and represents the vast majority of public investment in research—has increased funding allocations to sickle cell disease at a rate higher than the growth of its overall federal research budget. This includes a $200 million public private partnership with the Bill & Melinda Gates Foundation called “Cure Sickle Cell.” Launched in 2018, this effort is intended to “accelerate all aspects of the progress of curative therapies to the bedside.”
The work of addressing this biophysical manifestation of inequity in our society is not done. We need to get the cures that are being developed into patients, which means addressing issues of cost and delivery. We need more cures and treatments, recognizing that a single solution is unlikely to conquer this disease and its effects. And we need to reach the millions of patients around the world who do not benefit directly from the U.S.’s unparalleled biomedical research enterprise.
Still, this week’s announcement and the powerful example of private and public capital applied to this disease over the past 15 years shows that progress is possible.
This cure is not just a story about science conquering a terrible disease—although it is that in part.
It’s a story about how our society can improve in the unending pursuit of our highest ideals. That we can redeem a corrupt history of neglect and marginalization through commitment, ingenuity and collaboration. That we can together be part of bending the arc of history toward health, prosperity and justice for all.
Sam GillPresident & CEO Doris Duke Foundation