Judah Folkman: An Inspiration for the Tobin Project

A pioneering cancer researcher, Judah Folkman devoted his life to the pursuit of a powerful idea – that tumors recruit their own blood supply and that tumor growth could be halted by targeting this phenomenon. Ultimately, he overcame enormous odds to revolutionize the field of vascular biology.[1] His research lab was exceptionally productive, with a focus on projects that would address major unanswered questions and position researchers to make quantum leaps in knowledge.[2] Inspired by Dr. Folkman’s approach, the Tobin Project has modeled its own research strategy in part on his method, aiming to catalyze social science research on the most strategically important questions facing society.

Surgeon and Researcher

Dr. Folkman – a clinician, researcher, and professor – was recognized as a unique talent at an early age, selected in 1967 as the youngest-ever Surgeon-in-Chief at the Children’s Hospital in Boston.[3] A tremendously skilled surgeon, he observed tumors at close range in the operating room, and noted the surplus of blood they seemed to produce. Having conducted an experiment while in the Navy (1960-1962) that posed a puzzle about the relationship between blood flow and tumor progress, Dr. Folkman developed a theory: he hypothesized that tumors might be stimulating the development of new blood vessels, building their own blood supply to feed their rapid growth.[4] In 1981, he moved on from his position as Surgeon-in-Chief to focus full-time on research, establishing a lab at Children’s Hospital that would become one of the most groundbreaking cancer research laboratories in the world, both for the discoveries it generated and the strategies Dr. Folkman employed.[5]

Discovering Angiogenesis

In 1971, Dr. Folkman published an article in which he hypothesized that tumors “recruit their own blood supply” through a process he labeled “angiogenesis.”[6] If this process could be better understood, Dr. Folkman proposed in this and later papers, then the blood supply to tumors could potentially be cut off and their growth could be halted or even reversed.  

In an era when cutting-edge cancer research typically focused on the tumors themselves (and the cells that comprised them), Dr. Folkman’s focus on blood vessels was widely considered to be a diversion – a waste of time and resources.[7] His suggestion that the key to fighting cancer might lie with countering “angiogenesis” was met with much derision; indeed, many experts rejected the hypothesis outright while others alleged that even if such a phenomenon did exist, it was at most a sideshow.[8]

But Dr. Folkman persevered, driven by a deep commitment to his patients and by insights drawn from his dual experience as a researcher and as a practicing surgeon.  In 1984, Dr. Folkman and his colleagues published an article in Science about the first-ever purification of a protein that stimulated the growth of new blood vessels. It was with this discovery that his ideas finally began to gain currency in the medical community – two decades after his initial experiment in the Navy.[9] As Dr. Folkman put it, the publication “overnight converted most of the critics to competitors.”[10] By the 1990s, Dr. Folkman was recognized as a pioneer in the field of cancer research. And by 2004, when the FDA approved Avastin (an angiogenesis-targeting drug) for the treatment of colon cancer, Dr. Folkman and his lab were attracting twenty applications a week from scientists seeking to work in the lab and were producing some of the most important findings in the field.[11]

Through innovative experiments that often took years of painstaking work to complete, Dr. Folkman and the post-doctoral fellows who worked in his lab had been able to prove that tumors did in fact stimulate blood vessel growth (angiogenesis) and that angiogenesis inhibitors could be developed to retard the growth of tumors. These experiments and findings represented a quantum leap forward in cancer research and a powerful source of hope for cancer patients in dire need of new treatments.[12] Today, angiogenesis-inhibiting drugs originating in Dr. Folkman’s lab have been used to treat more than a million patients suffering from cancer and other diseases that involve the production of new blood vessels, such as macular degeneration.[13] “His vision and ideas literally changed the course of modern medicine,” says Dr. William Li, a former student of Dr. Folkman.[14]

Dr. Folkman’s Research Approach

Dr. Folkman’s dedication and resolve were remarkable. Over the course of four decades, he developed the field of angiogenesis nearly from scratch, despite sustained skepticism and outright hostility from many in the scientific community.[15] How did he accomplish so much against such great odds? According to Dr. Folkman, it came down to the questions he sought to answer. As he put it: “I have come to realize that the key is to choose a problem that is worth persistent effort.”[16]

Housed on the 14^th floor of Children’s Hospital in downtown Boston, Folkman’s lab was devoted principally to addressing questions with the potential to significantly advance understanding of cancer and possible treatments; it became an engine of productivity as a result.[17] In approaching a new project, researchers at other labs might start by asking: what is the probability that this hypothesis is right? Only if the probability were high would they then consider a second question – namely, the potential significance of the hypothesis for the real world, if correct.  But Folkman insisted that this two-step process be turned on its head.  In Folkman’s lab, only those “burning questions” that could have a major impact for patients were worth the lab’s energy and resources.[18]

Dr. Folkman’s focus on “burning questions” was rooted in a resolve that research in his lab would translate into benefits for patients. This focus on patients permeated the work he and his research team conducted in the lab, and served as necessary inspiration for the ambitious experiments the team was undertaking. Folkman would regularly bring patients into the lab to introduce researchers to individuals who had benefited from the lab’s  previous discoveries and who might one day be helped by the next generation of treatments.[19] People were always the focus of Dr. Folkman’s energies. In fact, even as a full-time researcher, he spent countless hours in the evenings returning the calls of cancer patients from all over the world who sought his guidance and support.[20]

To ensure progress in the lab was as rapid as possible for these patients, Folkman took an unconventional approach, encouraging his researchers to share works-in-progress, building an environment in which open feedback and collaboration were commonplace. Walking through his lab he would smile and tell reporters that he was “conducting an orchestra here. I’m listening to the music.”[21] While joint research projects and co-authorship were becoming more common, the culture of collaboration in Folkman’s lab nevertheless ran counter to the academic incentives pressuring the post-doctoral researchers to publish primarily as sole or first-authors. In the 1970s, young researchers had often been told by their advisers to steer clear of Folkman’s lab, with its atypical norms and long-shot projects.[22]

Indeed, it was a constant challenge for Folkman to motivate his post-doctoral fellows to take risks on major questions, where potential payoffs were large but relatively unlikely. To underscore the types of questions truly deserving of the lab’s attention, Folkman set up what would become a famous whiteboard in his lab. The whiteboard was filled with questions that others in the field might write off as either irrelevant or too big to tackle, but that were crucial to understanding and treating cancer and other diseases. At Friday research meetings, Folkman would stand at the whiteboard and remind the scientists in his group that while these questions might involve risky research projects, they could not be more important to patients who were suffering. When a lab member accepted the challenge to take up a question on the board, Folkman would put his or her initials next to the question, where they would remain until the question was answered. The whiteboard thus became an archive of fundamental questions in the field and the work that was yet to be done.[23]

Influence on the Tobin Project

Inspired by the productivity and innovation of Judah Folkman and his research laboratory, the Tobin Project has sought to build elements of his research process into its work in the social sciences. Perhaps most importantly, Tobin Project research inquiries aim to pursue questions with the potential to significantly improve society, avoiding narrow research queries focused simply on gaps in a particular literature. To identify these questions, the Tobin Project models its research meetings in part on Dr. Folkman’s lab. As part of every research initiative, on subjects ranging from national security to economic inequality, the Tobin Project encourages scholars to brainstorm and focus in on the most important unanswered questions in the field, recording these questions on whiteboards at scholar workshops and on an online “whiteboard” shared with the Tobin community of scholars. Moreover, presentations at Tobin Project meetings often feature early-stage work and collaborative projects, as researchers are encouraged to draw on the insights of their colleagues across multiple disciplines. In an effort to motivate research rooted in the real world, as Folkman was able to do by bringing patients to the lab, the Tobin Project invites policymakers and practitioners to participate in the social science research process – not just at the end-stage as an audience for completed work, but from the earliest stages of a new inquiry. 

“Dr. Folkman’s entire career was a testimony to this concept of the power of an idea,” says Marsha Moses, a former colleague of Dr. Folkman. “He not only had the intellect to understand a problem, but he had the courage to really focus on . . . huge questions whose answers would have a profound effect on people’s lives.”[24]