I was in high school when I first encountered the ruthlessness of the number one killer in the U.S. A close friend of mine, then only 16 years old, witnessed his father having a heart attack while checking the mail. Despite desperate attempts at CPR on the driveway, he wasn’t able to save his dad, a seemingly healthy man in his early 40s. That event put me on a path to become a cardiologist. Twenty-five years later, as a physician at Massachusetts General Hospital in Boston, I’m still seeing young patients having heart attacks, though they often have nothing in their health profiles to indicate increased risks.
As a preventive cardiologist, I wish I had a better way to identify patients who have a heightened risk for heart disease earlier so that they can take action before it’s too late. Prevention is the best medicine — it saves lives and health care dollars — but in our current paradigm, we’re focused on treating conditions after they occur.
Fortunately, there is a new, effective way to better find those at highest risk very early in life, well before they develop risk factors like diabetes or high blood pressure. My research group at Massachusetts General Hospital and the Broad Institute of MIT and Harvard, and many other labs, have been developing genetic tests that can predict disease risk well before disease becomes apparent, called polygenic risk scores.
These types of predictive tests and genetics-informed treatments hold enormous promise for the fight against heart disease, diabetes, cancer, and so much more. Polygenic risk scores have been developed for heart attack and other forms of heart disease, but they aren’t currently accurate for many segments of the U.S. population.
The only way to make these tools actually work for the diverse U.S. population is to study the health profiles of hundreds of thousands of Americans. Generating these profiles is precisely a key goal of All of Us, a federal precision-medicine research effort that’s now facing a potentially fatal funding cliff.
This world-leading initiative, launched in 2018, is recruiting 1 million volunteers from across the U.S. The project is collecting their health, medical, and genetic information, and making that large and invaluable dataset available to scientists like me so that we can find new drug targets and develop preventive tests from genetics for a wide range of diseases.
The data that All of Us has collected so far represents people from all across America, including those from rural and urban communities and from all walks of life. These people are helping us develop better polygenic risk scores and novel therapeutic strategies that will improve the health of all Americans for generations to come. But without full support from Congress, All of Us will only be able to generate roughly half of the genetic data it has promised. Less data from fewer communities means less accurate genetic tests and fewer new drugs that can keep people out of the emergency room.
All of Us faces a whopping 71% decrease in funding for the coming fiscal year, which starts Oct. 1, compared with its funding level just two years ago. That’s because a major source of its first round of funding, in the 2016 21st Century Cures Act, was designed with fluctuating budget levels over 10 years. This cut is but the start. With just two years left, the clock is nearly up entirely. While I am hopeful about recent efforts from two members of the House on a Cures 2.0 bill and from the Senate Appropriations Committee to restore All of Us funding to the FY 2023 level, it’ll be up to both chambers of Congress this fall to ensure this important program has stable funding to keep going.
All of Us is only half complete, and a loss of stable funding threatens its timeliness and impact. It is unclear how many more Americans will be able to sign up to contribute to this work; I worry that without the necessary support, recruitment levels will fall sharply and data generation will slow dramatically.
This funding loss will be a blow for preventive medicine in another way, too, by starving the drug development pipeline of much needed new drug targets that are rooted in human genetics. Many in the drug discovery world are familiar with the story of PCSK9 inhibitors, which lower LDL cholesterol levels to help prevent heart disease. These treatments were first approved by the Food and Drug Administration in 2015, just 10 years after genetic studies — similar to the ones that All of Us data can empower — suggested that the PCSK9 gene would be a promising target for cholesterol drugs. The big difference with the full set of All of Us data is that it would include many more people from underrepresented populations, which likely harbor disease-associated gene targets that are yet to be discovered. Without this entire diverse dataset, the genetics community will miss out on opportunities to generate more drug discovery success stories like the PCSK9 one.
This program has another advantage: maintaining and extending this country’s global edge in the life sciences. Other countries with nationalized health systems, like the United Kingdom and Finland, are making progress toward their own large genetic and medical datasets, or biobanks, that reflect the health status of their populations. While this information is useful for researchers all over the world, it is insufficient for developing the genetic insights, diagnostics, and treatments that are most relevant for Americans, because it doesn’t account for the population diversity and unique experiences and environments of the American people the way that All of Us data would.
All of Us is a big bet on a better future. Genomics-based tools will be critical for preventing and treating disease. Better prevention and treatment would save lives, livelihoods, and money: for heart disease alone, the American Heart Association projects annual inflation-adjusted health care costs will triple in the next two decades, from $400 billion to $1.34 trillion.
By restoring funding to All of Us, Congress can help deliver on the promise of a better health care system, and better health for all Americans.
Pradeep Natarajan, M.D., is the director of preventive cardiology and the Paul and Phyllis Fireman endowed chair in vascular medicine at Massachusetts General Hospital (MGH), associate professor of medicine at Harvard Medical School, and associate member of the Broad Institute of MIT and Harvard. MGH and Broad are both institutional recipients of All of Us funding to advance research. Dr. Natarajan does not receive direct funding from All of Us.
