D

r. Lee Nadler pounds the table. He chomps on a cashew. Then he leaps up to the whiteboard to scribble down the next big idea to keep tens of millions of federal dollars flowing his way.

Not that he’ll spend the money in his lab. He’s using the huge sums he brings in to change the way medical research is done, both at his academic home of Harvard and across the country. His goal: to break down the walls that divide highly competitive hospitals and encourage collaboration to speed up the process of turning lab discoveries into treatments and cures.

Nadler has come a long way from his days as a “street kid” in Queens who could barely read well into high school. Explosively energetic at 68, he’s an accomplished cancer researcher.

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And he has received more money in research grants from the National Institutes of Health in the past five years — nearly $120 million —  than anyone else in Massachusetts, except Eric Lander, the geneticist who runs the widely celebrated Broad Institute of MIT and Harvard.

Along the way, Nadler has inspired fierce loyalty from patients and mentees — and clashed with others through an aggressive and sometimes brash approach to making change. Deference isn’t part of his vocabulary: He once cursed out actor Billy Crystal, who was seated nearby at a Red Sox game, for cheering obnoxiously. And he once chided Bill Clinton for choosing a Big Mac for lunch; Nadler could hear the president chewing while they talked on the phone about the health of a potential judicial nominee.

Nadler is brilliant but “can be challenging to work with,” said Dr. Edward Benz, president of Dana-Farber Cancer Institute. He’s a forceful debater, Benz said, who will “argue a point right down to its finest edges.”

Above all, the oncologist is known for setting big goals and pushing relentlessly to achieve them.

“His greatest gift is that he’s not tethered to reality,” said Dr. Barbara Bierer, a senior vice president at Brigham and Women’s Hospital who has worked with Nadler for 30 years. “He sees where he wants to fly, and he goes there.”

Nadler directs the Harvard Catalyst program, which receives the NIH grants. He’s also dean of clinical and translational research at Harvard Medical School and a senior vice president at Dana-Farber, where he still sees patients once a week. If that’s not enough, he’s the principal investigator on a major football safety study sponsored by the NFL player’s union.

He moves quickly between these jobs, marching with a sporty black backpack down the street that connects the school with the hospital, his hair flipping up in the wind.

Lee Nadler at the Dana-Farber Cancer Institute in the early 1980s.
Lee Nadler at the Dana-Farber Cancer Institute in the early 1980s. Courtesy LeeNadler

From ‘street rat’ to Harvard dean

Born in 1947, Nadler grew up in a small home in a blue-collar neighborhood in Queens, without much money.

“We were street rats,” he told STAT in an interview in his office on Harvard Medical School’s historic quad.

“I could run fast,” he said. But “I didn’t know how to read.”  

A quirky guy, Nadler has outfitted his office with custom-ordered swiveling chairs to suit visitors of different sizes. Peering with intensity through purple spectacles, Nadler seemed to be in constant motion during an hour-long interview, jumping up at one point to move to a more comfortable seat.

His drive to keep moving stems in part from a difficult home life. His father called himself Dr. Bernard Nadler, but it turned out he had faked advanced degrees and never went to college. After an employer discovered his deceit, he stopped working at age 50, and stayed around the house, making life there uncomfortable, Nadler described in an extensive interview published by Baylor University Medical Center.

Nadler wanted to escape. So, he said, he went to the library at age 15 and asked the librarian for a book. At the time, he could read only comics. He spent two weeks paging through Pearl S. Buck’s “The Good Earth” with a dictionary, and went back for another. Within a year, he said, he was reading Dostoyevsky.

His family didn’t have much money for college, so Nadler enrolled in City University of New York for $34 a semester.

His first encounter with Harvard Medical School was bizarre: He showed up to an interview in 1968 soaking wet, teeth chattering from walking 3 miles in the sleet without a proper winter coat. Thinking he had no chance of getting in, he dared to argue with his interviewer about the Vietnam War. Then he stripped down to his underwear and put on scrubs while the interviewer dried his clothes in a pathology dryer, Nadler told Baylor. (He declined to retell the story, now that he’s a dean.)

The interviewer, Dr. Sanford Roth, fought for Nadler’s admission — and launched his career as a medical student and then doctor. As a researcher at Dana-Farber, Nadler became a pioneer in the field of immunology, making a key discovery that led to the cancer drug Rituxan.

Kings of the Hill

These are the top recipients in Massachusetts of National Institutes of Health grants, listed by principal investigator, from 2010 through November 2015.

Pressing competitors to cooperate

Nadler began his run as a major recipient of federal research funding in the summer of 2007, when the incoming dean of Harvard Medical School, Dr. Jeffrey Flier, called with a problem: Harvard was at risk of losing out on a major NIH grant.

The NIH had recently created a Clinical and Translational Science Award program meant to create new hubs to help scientists get past the many obstacles keeping them from turning lab discoveries into therapies for human beings.

Flier’s predecessor had assembled a team to work on the grant application, but it wasn’t going well and the deadline loomed. Nadler recalled Flier telling him that he was “the only one who could fix it,” though advisors had warned him that Nadler was “a piece of work.”

Nadler didn’t want the job. He looked at the application and told Flier it had “zero chance” of success.

The main problem, Nadler said, was that creating a new hub would require wrangling cooperation between five high-powered, highly competitive academic hospitals — Massachusetts General, Beth Israel Deaconess, Brigham and Women’s, Boston Children’s, and Dana-Farber — whose leaders rarely worked together.

Though most of those hospitals are connected by bridges and tunnels, “this place is the most siloed place in the world,” he said.

In the end, he couldn’t resist the challenge. Nadler pushed out some people who were working on the grant and brought in his own team to staff what he called a “war room.”

Nadler said he picked smart people who worked at the major hospitals, but who didn’t represent those hospitals. “The institutions weren’t going to come together — people were,” he said.

The group started in August, pulling 18-hour days, fueled by takeout falafel and Thai food as they brainstormed ways to force cross-hospital collaboration. (They did have a trump card: The hospitals stood to lose millions in NIH funding unless they joined the new collaborative model.) Crunch time was frenzied: As administrative lead Laura Weisel organized thousands of printed pages on a large table, grant writer Becky Ward took Nadler by one ear and sat him down on a couch so he wouldn’t interfere.

The process worked. They got the grant on the first try, securing $117.5 million from NIH to fund Harvard Catalyst over five years. Catalyst then redistributed some of that money to hospitals for clinical research.

Transforming medical research nationwide

Other money went to build tools to spur collaboration. Within 100 days of Catalyst’s launch in 2008, data whiz Griffin Weber, then the chief technology officer at Harvard Medical School, built an online platform called Harvard Catalyst Profiles, which lets anyone search profiles of 24,000 Harvard faculty. Clicking on scientists’ profiles shows a wealth of data, including papers they have authored, their most frequent collaborators, and even whose offices are nearest to theirs. And you can search by keyword to find an expert in a certain field (“fatty liver” was a recent popular search).

One key to Catalyst’s approach, Nadler said, is that “everything we build, we give away for free.”

The open-source software used to build Profiles is now being used by more than 30 universities, companies and federal agencies across the US.

Another Catalyst-funded project, a data warehouse called SHRINE (the Shared Health Research Information Network), lets scientists search electronic health records of 6 million patients across the five major Harvard-affiliated hospitals to find potential subjects for human trials. For instance, a researcher can type in a query and instantly find out how many adults over 55 are diagnosed with attention deficit hyperactivity disorder.

That software, also open-source, is being used by researchers at 32 institutions across the country, including Duke University, Cincinnati Children’s Hospital Medical Center, and the University of California system.

A third Catalyst project speeds up the process for setting up human trials. Before, researchers who wanted to include patients from multiple hospitals had to petition each hospital’s Institutional Review Board for approval, which could take weeks or months. Catalyst helped the hospitals set up “reliance” agreements, so if a scientist gets IRB approval from one hospital, other hospitals can choose to accept it. Now 36 institutions across New England and California participate in Harvard’s IRB reliance network.

The reliance agreements have been used to fast-track at least 1,500 clinical trials so far. For instance, after the Boston Marathon bombings, researchers used the system to set up a trial to study trauma-related hearing loss among 100 patients across eight hospitals. The setup took just three days, Nadler said.

The ‘bulldozer’ talks strategy

Former Red Sox CEO Larry Lucchino, who became a friend after Nadler successfully treated his cancer with a bone marrow transplant, called Nadler a “deeply caring guy” whose heart is “as big, or bigger,” than his brain. Lucchino routinely leans on Nadler to give medical advice to friends and relatives with cancer.

Nadler is also “a bulldozer,” Lucchino said: “He will tolerate no impediment or obstacle impairing his ability to treat his patients.”

Flier, the Harvard medical school dean, put it this way: He’s more intellectually aggressive about things than most people dare to be.”

Nadler has worked 100-hour weeks his entire life; he used to hold lab meetings on Sundays — at 5 a.m., according to his son, Eric Nadler, an oncologist in Texas. Eric described his dad as an avid gardener who collects microscopes and loves medical history, telling his son stories about the history of cancer at bedtime. He’s also an “exercise freak” who can “run anybody into the ground,” Eric said. Nadler has pedaled in the 200-mile Pan-Mass Challenge bike ride for the past 16 years, raising a whopping $760,000 for cancer research.

Nadler’s next big challenge is to win a second renewal of the NIH grant that fuels Catalyst with $24 million a year, supporting a staff of 160. Nadler and his deputies from across Harvard’s affiliated hospitals are already working on the next application, which is due in May of 2017.

A recent strategy session resembled a boisterous family dinner, held over tangerines, blue cheese, and nuts from Whole Foods. Decorum went out the window as Nadler leaned back with one foot on the table and interrupted with blunt pronouncements like, “You’ll never fix the minority problem at Harvard!”

He said Harvard can’t diversify its workforce quickly enough in time for the grant deadline, and should hatch new partnerships with historically black universities. In a lively and good-natured exchange, his deputies interrupted right back.

“We all talk over each other,” Nadler apologized.

An hour later, Nadler got a text message. He stopped the meeting.

“Can I tell you a story that is so unbelievable that I feel like I’m in a Fellini movie?” he asked.

The text was from a patient whom he had treated five years ago for Hodgkin’s lymphoma. Now the man is cancer-free, and Nadler, who befriends lots of his patients, had been goading him to “produce.” The patient had just messaged him to announce that he’s expecting a baby in May.

“Hodgkin’s went from a murderer,” Nadler marveled, “to now pretty much everyone’s cured.”

The text was a distraction from the day’s agenda. But in a way, it was the whole point.

For Nadler, getting the next big NIH grant means finding more cures. And he’s not going to stop until he does both.

Correction: A previous version of this story, and an accompanying graphic, mischaracterized Lee Nadler’s rank in NIH funding. The story also misstated the bedtime story he read his son.

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