From the Annals of NIH History: Lefkowitz

My Adventures as an NIH Yellow Beret

BY ROBERT LEFKOWITZ WITH RANDY HALL

Excerpted from A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist, by Robert Lefkowitz with Randy Hall (Pegasus Books, New York, 2021).

I stripped off my doctor’s whites and threw them in the hamper. As I dressed in my civvies, I was overwhelmed with bittersweet emotions. It was the last day of my internship at Columbia, and I was leaving medicine behind for a two-year research stint at the NIH. I strode out of the main door of Harkness Pavilion onto Fort Washington Avenue, where my wife Arna and our three children were waiting for me in a Dodge Dart that was overloaded with luggage. I climbed into the car, and we began the drive to Maryland.

I was 25 years old and had never lived anywhere except within a 10-mile radius of New York City. Have you ever left behind everything you’ve known? Have you ever set off on a journey feeling utterly uncertain about your future? That was how I felt driving out of the city that day.

By evening, we arrived in Rockville and I began to feel better. We moved into a townhouse with multiple bedrooms and a grassy backyard. The space felt positively luxurious compared to our cramped quarters in New York. We also felt rich: as an intern I had made $4,000 per year, but as an NIH fellow I would be making $12,000 even though my schedule would be much more relaxed. I was sad to be leaving the day-to-day practice of medicine but already enjoying the perks of my new lifestyle, with the major perk, of course, being that I got to be with my wife and kids rather than 9,000 miles away in Vietnam.

The Public Health Service–commissioned officers of that era who served at the NIH were known as the Yellow Berets. The sobriquet was a play on the Green Berets, with the color change meant to suggest we were too scared to fight. Avoiding service in Vietnam was not an act of cowardice, though. For most, it was an act of conscience. The war was immensely unpopular, and massive antiwar demonstrations in downtown Washington, D.C., were a common occurrence during my two years of service. Arna and I took our kids to several of these demonstrations, which we recognized as history in the making.

Young doctors across the country were desperate to avoid being shipped off to war, so the NIH had received thousands of applications that year for less than two hundred slots. The intense competition meant that those selected were the cream of the crop, and I felt honored to be part of this august group. One of the other Yellow Berets starting at the same time was my friend and medical school classmate Harold Varmus, and it was comforting to see at least one familiar face during my first week at the NIH….

The Yellow Berets were all medical doctors doing research fellowships, but we also performed clinical duties. We worked at the NIH Clinical Center, a building that was half research space and half hospital. As part of a rotation, every fifth night we would sleep in the hospital to attend to any medical emergencies that might arise. Most of the patients we saw in the Clinical Endocrinology Branch where I worked had been flown in from around the country with exotic endocrine disorders. My mentor, Jesse Roth, had developed the first radioimmunoassay for measuring growth hormone when he was a trainee in the lab of future Nobel Laureate Rosalyn Yalow and her research partner Solomon Berson. For this reason, many of the patients we saw had acromegaly, a disorder caused by excessive growth hormone levels, and Jesse was carrying out detailed studies of such patients as part of our inpatient service. These patients were flown in from all around the country and had characteristic enlargements of certain features, such as their jawbones and hands….

Other than my occasional duties as the officer of the day, I was mainly focused on research. My early days in lab were a complete disaster. One time, I was pushing a glass pipet through a rubber stopper when the pipet broke and deeply gouged my forefinger. This accident occurred in the evening, after most hospital staff had gone home, so there were no other physicians available to suture the wound. I sprinted to the emergency room of the Clinical Center, blood trickling down my hand, and found a nurse who assisted me as I sutured my own finger. Due to the fact that I was in severe pain, not to mention one-handed and out of practice, I did a lousy job. The aftereffects of this botched surgery would plague me for years to come. The incision appeared to heal, but then mysteriously flared up again every few months. Eventually, it broke down and began extruding tiny pieces of glass, with an X-ray revealing numerous additional shards of glass still embedded. Finally, an experienced surgeon performed an additional surgery to clean things out, allowing the finger to fully heal.

I survived my early struggles with help from my mentor, Jesse Roth. He was a nonstop dynamo of positive energy who kept everyone in the lab pumped up….

The project that Jesse and Ira [Pastan] had given me was to identify the receptor for a hormone known as ACTH, which is a key regulator of the stress response. For this project, the first thing I had to do was label ACTH with a radioactive tag, then separate the labeled hormone from the unlabeled. In theory, this sounds easy, but in practice, it was a titanic struggle….

I continued having technical troubles, but then suddenly, a year into my fellowship, a miracle happened: my experiments started working. The essential insight that led to my success was that I needed to ask others for help instead of just struggling by myself…. I sought out several expert chemists on the NIH campus to ask their counsel. With advice from these sages…I finally got traction in achieving chemical separation of the labeled ACTH from the unlabeled.

Once I finally had some pure labeled ACTH, everything else moved with breathtaking speed. In short order, I showed that the labeled ACTH was biologically active, and then rapidly developed one of the very first assays for studying the binding of a hormone to its receptor. Later in my career, I realized that this is often how research works: you experience nothing but failure for weeks or months, and then suddenly you overcome a technical hurdle, like in this case finding the right chromatographic system to separate the two forms of ACTH, and suddenly everything starts moving like wildfire. These were heady months, as I felt intoxicated by the knowledge that I was exploring new realms of research where none had previously trodden.

Read about more about Lefkowitz and three other Yellow Berets who became Nobel laureates (“From Yellow Berets to Nobel Laureates”).