Douglas Lowy
Doug Lowy received the Lasker Award for medical research, known as the “American Nobel.”

“I am a follower,” admits one of the leading cancer researchers in the world. It’s a slow Thursday night in Bethesda, Md., and Doug Lowy ’64 is having dinner at a little place called Chef Tony’s, where the crab cakes are celestial. Lowy works a few miles from here at the National Institutes of Health; he runs a prestigious lab focusing on viral agents in cancer. Tomorrow morning I’ll be at the NIH, trying to wrap my history-major head around complex molecular biology. Tonight, though, he’s brought me and his wife, Beverly Mock, here so we can all drink wine and share our stories. That’s how Lowy moves through the world: he is as personal as he is methodical.

At the table, Mock—who also runs an NIH cancer lab, hers studying environmental agents—laughs at Lowy’s “follower” remark, which he said with a shrug and a smile. Maybe it’s because she doesn’t quite believe him. Maybe it’s because that word can slant toward the pejorative. A blind follower. Someone short on originality. Really, how could a mere follower lead the National Cancer Institute? Or be the chief of its Laboratory of Cellular Oncology? Or, more flashily, win the “American Nobel Prize”?

That’s the nickname of the Lasker-DeBakey Clinical Medical Research Award: In the field, everyone knows that many Lasker winners go on to win the actual Nobel, too.

Lowy and his NIH colleague John Schiller got the 2017 Lasker for their pioneering work on the science behind the HPV vaccine. It protects against the sexually transmitted human papillomavirus. HPV usually clears up on its own, but sometimes it drives cervical and other kinds of cancers. In fact, HPV leads to more cancers than any other virus. Introduced in 2006, the newest version of the vaccine is now close to 100 percent effective against 90 percent of the infections that cause cervical cancers, and new versions of the vaccine could combat still more.

More impressive numbers: HPV infection rates have dropped 71 percent among teenage girls in the U.S. in the past decade, and the Centers for Disease Control and Prevention estimate that the vaccine can prevent 90 percent of HPV-generated cancers from ever developing. That’s 31,200 U.S. cancer cases every year, and untold lives saved—because of what Lowy and Schiller did.

At age 12, Lowy saw a film about Salk and his vaccine. “I knew zero about it, but what Salk and his colleagues said was crystal clear.”

You’d forgive anyone for acting superior with a legacy like that. As I will find out tonight and tomorrow, however, Lowy is a mensch: kind, funny, steady, confident without being arrogant, a people person who is scientific not just by occupation, but by character. He gives you proper warning if he’s going to digress, for instance, and never makes a statement without supporting evidence. So tonight, between bites of seafood stew, Doug Lowy lays out the many times he’s been a follower.

It goes all the way back to his parents. Frances Siegel Lowy and Milton Lowy were both doctors, and their younger son followed in their footsteps. “I think that I decided very early on that I wanted to be a practicing physician the way my parents were, because I liked what they did,” he says. “It was helpful, and they knew things. And I found it interesting.”

Lowy’s parents were second-generation Americans: his father’s parents had come over from Hungary, his mother’s from Romania. The name “Lowy” is the Germanic spelling of “Levy.” Lowy’s friend Stephen Mitchell ’64 was charmed by Lowy’s parents and their familial warmth: “Doug’s parents were very affectionate with him. That would have translated into a very dependable base.”

The Lowy family lived and worked in the Bronx and, as a boy, Lowy would flip through his parents’ medical literature, pitch in at their office when the nurse had a day off and even go to the occasional professional lecture. Once, his father couldn’t make it to a presentation on Jonas Salk, so Doug, then 12, joined his mom instead. “When the Salk vaccine was approved by the FDA, they had special closed-circuit programs, shown in movie theaters for doctors. So I went. And I knew nothing, zero about it, but what Salk and his colleagues said was crystal clear: There were three strains of polio virus. The Salk vaccine had all of them, but it was much more protective against two of them and less protective against the third.”

Lowy would later follow his mother’s example by enrolling at her alma mater, the NYU School of Medicine, where she’d been a rare female student, graduating in 1939. Salk had been her classmate.

That night at Chef Tony’s, light glancing off his wine glass, Lowy visibly relished sharing several Salk-related stories. “My mother loved to point out that, at NYU class reunions, ‘Jonas Salk comes over and says hello to me.’” He laughed at the memory, and followed that with this: “When Salk was nearing the end of med school, he told his classmates, ‘I have the opportunity of taking a year off and doing research.’ And everyone told him that it was the stupidest idea that they had ever heard.”

Lowy loves the research anecdote for its irony, but also because it points to the unpredictables in his own career. “I had a disconnect,” he says. “It was not until I was in medical school that it occurred to me that physicians did research. I thought that researchers were always Ph.D.s.” But NYU had gained a reputation for its emphasis on medical research, and Lowy was inspired by a class with microbiologist Jan Vilcek, with whom he later helped research interferon, a vital immune system protein. And so it came to pass that Lowy chose a life spent in the lab, rather than on rounds.

A few years ago, Lowy headed to La Jolla, Calif., to attend a cancer research conference at the Salk Institute for Biological Studies. In his remarks there, he shared the Salk year-off-for-research joke, feeling touched to recall his mother and his own journey. But it turns out he’d heard that anecdote not from his mother but from Nathan Mitchell, the father of his Amherst friend Stephen Mitchell. In fact, Nathan Mitchell was also at NYU with Lowy’s mother and Jonas Salk.

And how did Lowy end up at Amherst in the first place, I asked. He grinned: “I followed my older, smarter brother.”

That’s Martin Lowy ’61. “Marty liked Amherst, so I applied as well,” Lowy recalls. “I was impressed by how intelligent the students were, but that they were not one-dimensional.”

When Doug Lowy was still in high school, his brother brought home various college friends over break. One was Harold Varmus ’61, who lived on Long Island and sometimes caught a lift back to New York. The Lowys even took Varmus with them on a ski trip one weekend.

Like Doug Lowy, Varmus would go on to win the Lasker Prize (in 1982). Later that decade, he became one of Amherst’s five alumni to win the Nobel Prize: the 1989 Nobel in Physiology or Medicine was jointly awarded to J. Michael Bishop and Varmus for their discovery of the cellular origin of retroviral oncogenes—a breakthrough that would drive Lowy’s career, too. A retrovirus is a group of RNA viruses that can uniquely implant their DNA into a cell in order to replicate, and thus turn a normal gene into a cancer gene, or “oncogene.”

Given his prodigious scientific feats, you’d assume Doug Lowy majored in a science at Amherst. But no. Another instance of following: “My parents had been chemistry majors and felt that I would get plenty of science when I went to medical school, because I already knew I wanted to do that,” says Lowy. “What they felt had been missing, in their education, was learning about humanities.” To compensate, in part, the Lowys subscribed to a kind of book-of-the-month club with an art history theme, and both boys looked forward to the arrival of each sumptuous volume. Marty, who became a lawyer, banker and author, also took a couple of art history classes at Amherst, and even introduced one of his professors to Doug.

That was Frank Trapp, professor of fine arts, a painter and sculptor, and one of the creators of the Mead Art Museum. Trapp became one of Doug Lowy’s most important influences at the College. Though he made sure to take enough pre-med courses to apply to medical school, Lowy majored in art history. Trapp was the adviser for his thesis, titled “The Salon of 1846: A study of French painting during the July monarchy.” In his acknowledgments, Lowy thanked Trapp for his “indispensable advice,” which, as I found out, had un sens plus profond—a deeper meaning.

But now, like Lowy, let me warn you that I’m about to digress. Before we met, I emailed Lowy some questions, including one asking what he did outside of class at Amherst. He replied, “As a student, I focused on the academic courses I was taking (every semester was challenging), friendships and dating. I was not a loner, but was not involved in formal extracurricular activities.”

This rang true then and now: Lowy is a man centered by work and relationships. He is a father of five within a blended family: three children (including Stephanie ’95) from his first marriage, and two children he’s raised with Mock, after their biological father died. And his Amherst friendships are still robust today. He does long catch-up phone calls with Dan Rosenn, Bob Leibowitz and Roger Hirschberg, all from the class of 1964, and they take a yearly trip with their spouses. “Doug has always found time for being interested in people, for being compassionate,” says Hirschberg. The first two words that came to his mind about Lowy? “Intense. Generous.”

Which takes us back to his thesis adviser. At Chef Tony’s, Lowy talks long and thoughtfully about all the ways Amherst inspired him. One of those stories brushed on his thesis. “I had a big growing-up moment my senior year,” Lowy says. “I’d had a certain amount of personal unhappiness because of my girlfriend. Nothing more serious than that, but for me it was very serious. It was probably March, and my thesis was due in May, and I hadn’t written a word. And I said to Professor Trapp, ‘You have got to give me a deadline, so that I will get a first draft written.’

“And you know what he said to me? ‘I will not. You are not writing this for me. You are doing this for you. You have to find it within yourself.’ It was a watershed moment for me. It started getting me away from doing things to please other people, and much more doing things because I thought it was important for me.” In other words, he began following his own counsel.

Douglas Lowy
Lowy made sure to take pre-med courses in college, but his Amherst major was art history.

The National Institutes of Health, America’s chief agency for biomedical research, looks like a sort of massive, slightly confused college campus. About 18,000 employees are split between some 70 buildings, a mixture of towering modernist labs, traditional brick structures and fancy Greek revivals. Shuttle buses ferry patients about, to take part in clinical trials. Each building is either sternly labeled by number (Lowy works in Building 37) or given a meaningful name, often to honor a legislator who once pushed through a round of funding.

The first two words that come to a classmate’s mind about Lowy? “Intense. Generous.”

We’re sitting in Lowy’s impressively windowed office, high above the trees. The Lasker Award, a gold winged trophy, perches on the windowsill, and the walls are lined with photos of charismatic locales. Lowy’s favorite depicts Italy’s Laurentian Library, designed by Michelangelo. Today, Lowy wears khakis, a blue button-down and a lanyard with his NIH badge. As he eats the lunch he brought from home, he walks me though his professional life up to and after the HPV vaccine.

He trained in internal medicine at Stanford and dermatology at Yale, finishing his studies in 1972. This was the time of the Vietnam War draft, and, to fulfill his selective service requirement, the draft board allowed him to do a two-year stint at the NIH. It turns out Harold Varmus ’61 struck much the same bargain, as did John Gallin ’65, now the NIH associate director for clinical research. Back in the 1970s, because these alums had each avoided going to Vietnam, Varmus gave their group a darkly ironic name: “the yellow berets.” All would apply their considerable talents to government careers, staying at the NIH long after the draft board mandated, with some stints at universities, declining to sign on with the pharmaceutical industry and its glossier salaries. In fact, in 2007, Lowy (along with Schiller) won the Federal Employee Service to America Medal.

Lowy has now been at the NIH for 46 years. And Amherst has had a snowball effect. Fellow alum (and English major!) Varmus was director of the National Cancer Institute from 2010 to 2015—and he chose Lowy as his deputy. After Varmus left, Lowy became acting director. Says Schiller, “A lot of people are top-notch scientists or top-notch administrators, but not many are top-notch at both. Doug is. And he gets twice as much done as anyone I’ve ever worked with.”

Lowy’s HPV work with Schiller has drawn the most attention, but Lowy’s other efforts have also advanced our understanding of cancer. At first he worked in the lab of the famed Wallace Rowe, who studied retroviruses that cause leukemia in mice. By 1975, Lowy, in his own lab at the NIH, was one of those at the forefront of working on the RAS family of oncogenes. RAS gets its name from rat sarcoma, since the viruses that contain RAS were first discovered in rats. The three RAS genes in humans are among the most prevalent oncogenes, contributing to some 30 percent of all tumors. “Doug’s early work with RAS was just as phenomenal as his later work with HPV,” says Peter Howley, a Harvard Medical School professor who studies papillomaviruses.

In the 1980s, Lowy, with Schiller, turned his attention to papillomaviruses, then much less studied than retroviruses. Eventually, they set out to create a human vaccine—though they had no background in vaccinology. There was no viable way to do that before trying a vaccine on animals. Thus they began scrutinizing the bovine papillomavirus (BPV), which causes warts in cattle, and tried to understand how a BPV infection causes these changes. Through trial and error, they discovered that the proteins that form the capsid, or outer shell, of BPV could produce virus-like particles (VLPs) that closely mimic the original virus, with one stop-the-presses exception: VLPs are not infectious, for they lack viral genetic material that replicates itself, and so can’t cause cancer.

Even better, because VLPs so closely resemble HPV’s structure, they could maybe “fool” the body into triggering a protective antibody response against infections. Here’s a metaphor an art history major would appreciate: VLPs are like Han van Meegeren’s forgeries of Vermeer paintings, so uncanny they duped experts and sold for a fortune as if originals. In 1991, Reinhard Kirnbauer, a postdoctoral fellow on Lowy and Schiller’s team, began trying to make bovine VLPs. To do this, the team homed in on two promising proteins on the BPV microbe’s surface, L1 and L2. L1 proved more viable, and rabbits   were then injected with the BPV L1 vaccine. “We got sky-high levels of antibodies, a thousand times higher than what we looked for, levels you almost never see when you develop a vaccine,” says Schiller. “That was super exciting.” They tested it further over the next decade, each time refining the vaccine.

Yet when it came to testing the vaccine in humans, progress did not follow a clear path. I could chronicle a thousand crossroads, but let this one stand in for many: Lowy and Schiller figured they could transfer their BPV L1 success to an auspicious common strain of HPV, tagged as HPV16, and make virus-like particles from its L1 protein. But it didn’t take. Through much back-and-forthing, they hit on the notion that the problem lay in the standard source of the HPV16, which came from a cancerous sample: cancer cells are notorious for jumpstarting genetic changes, and perhaps the source had been compromised. So they tried working with HPV16 cells that only cause a benign infection, rather than a cancerous one. That made one crucial difference: it turned out the L1 protein from this new source featured a lone amino acid that was crucial to assembling the VLPs needed for a human vaccine.

I asked Schiller to characterize Lowy’s role in this process. “Some scientists have so many ideas, but they can’t focus on one,” he says. “Some know all the literature but can’t have any original ideas. Some are very into control so never move ahead and discover something. But Doug does all those things well.”

A long series of clinical trials began in 2001, run by Johns Hopkins, Merck and GlaxoSmithKline. In one, 800 volunteers received the vaccine and none developed a cervical infection—while 41 of those in the placebo group did. In 2006, the FDA approved the first vaccines for the virus, which tackled HPV 16 and HPV 18. After more than two decades, the researchers had triumphed at last.

On a whim, I asked Stephen Mitchell, an eminent translator of works like Gilgamesh and the Book of Job, if there are any lines from his works that apply to his Amherst friend. He consulted his 2007 version of the Tao Te Ching, and sent these: “Do you have the patience to wait / till your mud settles and the water is clear?”

But the vaccine’s rollout, like most rollouts, has not been perfect. It arrived in an era when there was a small but forceful backlash against vaccines in general, and when you add the issue of sex, the optics get more uncomfortable. To consent to give your children the HPV vaccine, you have think of them as future sexual beings. (The vaccine is recommended at age 11 or 12.) Some parents also worried that the vaccination might be a license for young adults to be sexually active.

Like most rollouts, this one has not been perfect. It arrived in an era when there was a small but forceful backlash against vaccines.

Another complication centered on the issue of race. Though HPV16 and HPV18, the strains targeted in the first vaccine, are the most common overall, African-American females are about 50 percent less likely to be infected by 16 and 18 than non-Hispanic white females. Subsequent vaccines tackled more strains, with the newest version, Gardasil 9, combatting nine, including the three most prevalent in the black female population. Learning all this prompted me to ask Lowy about Henrietta Lacks. She’s the African-American woman who died of cervical cancer in 1951, and whose “HeLa” cells, without her knowledge or consent, lived on to help scientists develop the polio vaccine, study HIV/AIDS and more. When Lowy presents on his work, he often ends by showing a picture of Lacks. HeLa cells carry evidence of HPV18. Had the first vaccine been available in her lifetime, he tells his audiences, she would have lived.

As of May 2017, 270 million doses of the HPV vaccine had been given out. This sounds remarkable, but it lags well behind the rates of older vaccines: In 2017, 49 percent of U.S. adolescents were up to date on the HPV vaccine, versus 93.7 percent for polio. Apart from their lab work, Lowy and Schiller have gone at these distributive problems holistically, consulting with groups such as the World Health Organization on how to promulgate the vaccine.

As Lowy says, “John and I have not just stayed in our corners.”

Douglas Lowy
Lowy graduated from New York University's medical school in 1968.

It’s Friday, the day when Lowy’s “growth lab” has its weekly meeting, when a half dozen scientists share their latest findings on how cancer viruses replicate and Lowy helps steer their next steps. The slides on the wall carry daunting titles like this, from team member Xiaolan Qian: “Hyperphosphorylation of ECT2 in vitro by endogenous kinase in the IP pellet.” When we’re back in his office, Lowy explains what it means: Among many parallel investigations, his team is exploring another promising protein-coding gene called ECT2. Phosphorylation is a signaling mechanism a cell uses to regulate activities including cell division. When phosphorylation occurs, it promotes cancer. A kinase is a kind of enzyme that regulates other proteins by phosphorylating them.

“It’s like a switch,” Lowy says. “It activates another gene that sends a cascade of signals.” The big picture here? The study of the role of proteins in cancer is one of the more promising areas of research right now.

We are winding down our time together, but I can’t leave before posing two more questions. First, I ask how it feels to have won the Lasker. “I spend very little time thinking about it,” Lowy answers. “Don’t misunderstand me. I’m ecstatic that the HPV vaccine has affected the health of the world. But researchers can’t dwell in the past. If you stand still, you’re going backwards.”

My second question concerns retirement; he’s 76, so I ask if it’s on the horizon. Lowy has a choice comeback: “I am committed to not working more than a year after I die.” I laugh, and he offers to drive me to the Metro. On the way, we talk about the vacation he and Bev are taking with all the kids and grandkids. Then we say goodbye, and I watch him hurry back toward his work. There are so many ways to save lives, after all, and Doug Lowy must follow each to the end. 

Katharine Whittemore is Amherst magazine’s senior writer.

Lowy at Amherst

Graduated: magna cum laude.

Favorite professors: Frank Trapp in art history, William Kennick in philosophy, Peter Serenyi in fine arts and Ben Ziegler and Earl Latham in political science.

Thesis: “The Salon of 1846: A study of French painting during the July monarchy.” It analyzes one of the huge art salons—with 20,000 visitors a day—held during the 12-year reign of Louis Philippe.

What he didn’t like about Amherst: That it was all male. “It was the only part of Amherst I never adjusted to. I felt that it was a very artificial atmosphere.”

Three Lessons He Learned in College

  1. Defy your biases with rigor. “Ben Ziegler, who taught classes on American government, trained as a lawyer before he got his Ph.D., and whatever you argued in class, he could argue the other side,” recalls Lowy. “This helped me more than anything else to understand that there can be at least two different perspectives on almost any problem.”

    How this lesson played out later:
    “I always recognize and try to design experiments that test your hypothesis in a way that not only can help support your hypothesis, but also can refute it.”

  2. Own what you don’t know. As a sophomore, Lowy prepped for his junior year in France by sitting at the French table at Valentine Dining Hall. “Periodically, President [Calvin] Plimpton would sit with us,” he recalls. “What impressed me was how terrible his French was! But he was not self-conscious. I said to myself, ‘I hope that I’ll have enough self-confidence to stick my neck out in areas where I don’t know much.’”

    How this lesson played out later:
    In one of his early lab jobs, Lowy bartered with another lab worker to compensate for where each was lacking. Lowy taught him about mammalian cell cultures and culturing viruses, and he taught Lowy advanced molecular biology.

  3. Good things can come from bad. Lowy wanted to apply to the Sweet Briar Junior Year in France program, but thought his C+ in French literature might hurt his chances. So he went to the instructor and said, “If I could get a positive letter from you, it would go a long way, because I didn’t get a good grade in your class.” Lowy suggested they do a reading course, one-on-one, and if he did well, he’d get the letter. Which is exactly what happened.

    How this lesson played out later:
    In his first post at the NIH, Lowy spent weeks preparing a large batch of virus and, as was customary then, labeled it radioactively, to make it easier to detect the virus. “At 8 on Saturday night, I dropped it on the floor. All of that work was ruined! And it was a radiation spill!” He decided to scan the literature for better ways to prepare virus. And that’s how he came across a 1973 paper by Harold Varmus ’61 that broke new ground on the study of viral genomes—which pushed Lowy further down the path that led to the HPV vaccine.

Photo Credit: Ryan Donnell