Tracing the Path from Basic Research to Transformative Therapies

Investments in basic research have a long track record of paying off in the form of new therapies, but often only after decades of work. This model of drug development — built on a long-standing partnership between academia and the federal government — has paved the way for life-saving treatments by allowing scientists to uncover the inner workings of cells and molecules.

“Almost all the transformative discoveries that changed our view of the physical world, and subsequently improved our lives, can be traced back to [fundamental] research,” wrote Nobel laureate William G. Kaelin Jr., the HMS Sidney Farber Professor of Medicine at Dana-Farber Cancer Institute, in a recent commentary.

Proposed cuts to federal funding for science raise an urgent question: What could be lost if this funding decreases or disappears?

A long-term investment

A 2018 analysis in Science Translational Medicine illustrates the power of long-term investment in fundamental research. Mark Fishman, MD ’76, a Harvard professor of stem cell and regenerative biology, and colleagues traced the roots of twenty-eight of the most important drugs approved by the Food and Drug Administration (FDA) between 1985 and 2009. They found that 80 percent stemmed directly from basic discoveries made in the lab, often by scientists trying to understand a biological process or disease. On average, it took more than three decades for a basic discovery to become an FDA-approved drug.

For example, the authors highlight the development of ACE inhibitors, the first of which was approved by the FDA in 1981. More than forty years earlier, scientists working in academic labs discovered a hormone — later named angiotensin — that raises blood pressure. Persistently elevated blood pressure, or hypertension, affects nearly half of U.S. adults and can damage the heart, brain, and other organs. In the 1950s and 1960s, academic researchers learned that an enzyme called ACE alters angiotensin in a way that causes the hormone to narrow blood vessels and increase blood pressure. Furthermore, they determined that a protein found in the venom of the Brazilian viper could block ACE activity. It wasn’t until the 1970s that a pharmaceutical company took up the charge and began testing compounds that could inhibit ACE, relaxing blood vessels and lowering blood pressure. The result? A new class of drugs that today includes ten FDA-approved medications. In the United States, over forty million people take these drugs daily to treat high blood pressure, heart failure, and kidney disease.

“Today’s most transformative medicines exist because of fundamental discoveries that were made without regard to practical outcome and with their relevance to therapeutics only appearing decades later,” the authors wrote.

A number of these medicines have roots in basic research conducted within the HMS ecosystem. The following examples illustrate both the long timeline and potential payoff of investing in fundamental research.

Immune checkpoint inhibitors

Therapies called immune checkpoint inhibitors have transformed cancer treatment. A pivotal chapter in the story took place in labs at HMS and Dana-Farber. In the 1990s, Arlene Sharpe, MD ’82 PhD ’81, chair of the HMS Department of Immunology and Kolokotrones University Professor, and her husband, Gordon Freeman, MD ’79, HMS professor of medicine at Dana-Farber, defined the PD-1/PD-L1 pathway that some cancers exploit to evade the immune system. Their research revealed key molecular details of how cancer cells disable immune defenses — and more importantly, how this mechanism could be blocked. Their work was critical in the eventual design of PD-1 and PD-L1 therapies for cancer that restore the immune system’s ability to spot and destroy tumors. The FDA approved the first PD-1 immune checkpoint inhibitor in 2014. Today, these therapies are approved for more than twenty-five cancer types and have improved outcomes for millions of patients.

Gene editing for sickle cell disease

Since the 1980s, HMS researcher Stuart Orkin, MD ’72, the HMS David G. Nathan Distinguished Professor of Pediatrics at Boston Children's and Dana-Farber, has been studying the basic biology of sickle cell disease. In this genetic condition, misshapen red blood cells block blood flow and quickly break down, causing severe pain and organ damage. Orkin and researchers in his lab focused on how red blood cells make hemoglobin — the oxygen-carrying protein that is defective in sickle cell disease. In 2008, Orkin and colleagues identified a gene that normally shuts off fetal hemoglobin, a version of the protein that is not affected by sickle cell. They hypothesized that if they could somehow keep the healthy, fetal form of the protein active, they could treat or even cure the disease. With the advent of CRISPR/Cas9 gene-editing tools, Orkin’s basic research findings suddenly had a pathway to the clinic. The result: CASGEVY, the first CRISPR-based therapy for sickle cell disease, which was approved by the FDA in 2023.

GLP-1 therapies

Basic research played a central role in the development of GLP-1 therapies, which have transformed treatment for type 2 diabetes and obesity and are increasingly showing promise for other conditions. Much of the early work on GLP-1 was carried out by Joel Habener, professor of medicine at HMS and director of the Laboratory of Molecular Endocrinology at Massachusetts General Hospital. In the 1970s, Habener used genetic tools to identify GLP-1 as a hormone that helps regulate blood sugar. Later, he and colleagues characterized the biology and mechanism of GLP-1, including how it responds to food intake to alter the release of insulin and glucagon in the body — two hormones critical for maintaining healthy blood sugar levels. These findings informed the subsequent design of therapies that mimic GLP-1’s effects in the body. The FDA approved the first GLP-1 medication for type 2 diabetes in 2005 and has approved multiple others for diabetes and obesity since. As of 2024, around 12 percent of U.S. adults had used one of these drugs.

Together, these examples encapsulate the impact of therapies that have emerged from basic research since 1945 — and underscore the risks to scientific progress should federal funding slow or stop.

As Kaelin noted in his commentary, killing fundamental research — “the science golden goose” — would have profound consequences for the United States and for humanity.

“We owe it to future generations to ensure this does not happen,” he wrote.

Catherine Caruso is a science writer in the HMS Office of Communications and External Relations.