Like Md.'s pawpaw tree, groundbreaking science takes time to bear fruit

Last week, as my colleagues and I celebrated the Nobel Prize recognition for Kyoto University immunologist Tasuku Honjo — who was a postdoctoral fellow at the Carnegie Institution for Science’s Department of Embryology, where I work, in the 1970s — I reflected on how, like Maryland’s native pawpaw trees, groundbreaking science takes time to bear fruit.

Dr. Tasuku and his co-laureate, James Allison of the University of Texas Anderson Cancer Center, were recognized for discoveries of two separate “brakes” on the immune system’s abilities to recognize tumor cells as a threat. Similar to how a vehicle’s brakes prevent it from accelerating out of control, these brakes hold the immune system back from recognizing our own bodies as a threat — called an autoimmune response — but they also prevent the body from fighting cancer as hard as it can. These remarkable discoveries led to the development of therapies that can release these brakes, stimulating the immune system to attack tumor cells and to fight off advanced cancers.

A week ago, four and a half decades after sending Dr. Tasuku out into the world armed with great training and high expectations, Carnegie developmental biologist Don Brown, one of my predecessors as department director, had the distinct pleasure of congratulating his former mentee on receiving science’s greatest honor.

“The time I spent in Carnegie has always been my best experience,” Dr. Tasuku responded in an email, noting that Don’s work galvanized his decision to pursue molecular immunology.

Of course, many other scientific collaborators influenced Dr. Tasuku and contributed to his achievements, which have led to breakthroughs in cancer treatment. Carnegie cannot claim the corner market on inspiration. However, last week’s excitement provides an excellent illustration of how the type of research my colleagues and I do can take decades to impact society or to receive broad recognition.

For another example, in August, more than 20 years after my former Carnegie Embryology colleague Andrew Fire and his UMass collaborator Craig Mello discovered double-stranded RNA can act as a gene silencer, the U.S. Food and Drug Administration approved the first-ever treatment that deploys this RNA interference process to help patients.

Back in 1997, Andy and Craig revealed that specially designed RNA could disrupt the flow of information from DNA to RNA that forms the central dogma of our field. For this work, they shared the Nobel Prize nine years later.

This kind of discovery forms the building blocks of what we call basic research — science for the sake of discovery. It enabled researchers like me to “knock out” specific genes, preventing them from being translated into proteins, and then observe how this disrupts normal physiological processes, determining what the gene does.

But it also illustrates that the gap between the search for fundamental scientific truths and the quest “to benefit humankind” — as stated by my institution’s founder, Andrew Carnegie — is more-narrow than we often give it credit for being.

In my field, we frequently debate the value of so-called translational research, which is designed from its inception to yield specific medical benefits, against the value of pursuing discovery for its own sake.

And yet this discourse often overlooks a truth so eloquently stated by one of my institution’s former presidents, Vannevar Bush, in his seminal work, “Science, the Endless Frontier”: Basic research “provides scientific capital,” he wrote. “It creates the fund from which the practical applications of knowledge must be drawn.”

It’s not that those of us who focus our efforts on discovery science lack an interest in drug development. It’s that we recognize our efforts are laying a foundation that could someday lead to a medical advance, but perhaps not for many decades. Without this reliable bedrock in place, no triumph in health outcomes can be counted upon to occur.

Yixian Zheng (yzheng@carnegiescience.edu) is director of the Department of Embryology, the Baltimore campus of the Carnegie Institution for Science.

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