John Maraganore opened up an envelope in 1994 that changed his life. Inside were the results of the pivotal study of an anticoagulant drug Maraganore had created in the lab. It was the star prospect for Maraganore’s employer, Biogen. If the drug, bivalirudin, worked, Biogen might have its first product—and Maraganore, the glory of designing it.
The news, however, was bad. Bivalirudin failed the study. Biogen jettisoned the drug altogether, and moved on to become the world’s leader in multiple sclerosis treatments.
And Maraganore, the classic geek scientist obsessed with basic research, would never work at the lab bench again. Instead, Biogen leadership forced him down a new path, one that would transform him into a successful biotech business executive. He would authorize strategic decisions, weigh multi-billion dollar deals, handle the fates of hundreds of employees—and even find a way to bring bivalirudin to market. And ultimately, he would become one of the driving forces behind a new, high-risk, and high-reward, field of science—RNA interference (RNAi)—that aims to “silence” disease-causing genes.
Indeed, 20 years later, Maraganore now is synonymous with RNAi. He’s the CEO of Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: [[ticker:ALNY]]), which has grown from fledgling startup to the biggest RNAi operation in the world.
And soon, another crucial envelope is coming for Maraganore. After burning through more than $600 million of invested dollars and enduring a series of highs and lows, Alnylam is running its first Phase 3 trial, with a drug called patisiran. The drug treats a rare condition that causes proteins to clump up in the body and stifle organs. Successful results will turn Alnylam from an expensive 13-year-long science project into a real revenue-generating pharmaceutical company with many more opportunities—and help validate the whole field of RNAi.
If patisiran fails? The chorus of those who doubt RNAi will grow louder.
“That’s fine,” Maraganore says. “That’s just the price of leading an effort.”
Indeed, Maraganore has never played it safe. He could have followed the path of his father and brother, and become a doctor with a stable income. He chose high-risk research instead. He could’ve stayed at Biogen, or later, Millennium Pharmaceuticals—established, stable drugmakers. Instead, he chose to lead a tiny startup pursuing a new field of science. He could have kept quiet when Novartis backed out of RNAi research earlier this year. Instead, he publicly blasted Big Pharma and criticized its ability to innovate.
“John is very much not risk-averse. That’s always been his MO as a scientist—he was a very bold scientist,” says Third Rock Ventures partner Kevin Starr, a longtime friend of Maraganore, a colleague at Biogen and Millennium, and a fellow Alnylam boardmember. “Alnylam has survived because he’s looked at it as one of his children and he’s put all that passion in there.”
Still, Maraganore is unfailingly self-effacing. He’s quick to point out his failures (there’s been “tons,” like deals he decided against that burned him down the road) or weaknesses (like running the day-to-day operations of a company). He’ll often point out others who are more qualified than he is to do a job—even if, in potential merger discussions, that may cost him his own. He’ll promote people past him. Starr, for instance, started out as his employee, but became his boss after a promotion Maraganore endorsed. He loves travel and good food, a glass of wine and a cigar, and a game of pool.
“John’s a fun guy,” Starr says, ”[and] he’s been successful by being a giver.”
And by pursuing his passions despite the risks. Maraganore (pronounced mare-a-ga-NOR-ee) was born in 1962 in Chicago, the son of two Greek immigrants and the second of three children. The family started out in a 2-bedroom townhouse in Rogers Park, on the far north side. When Maraganore’s father’s career as a pathologist took off, they were able to move to the upscale suburb of Skokie when Maraganore was about eight years old.
Much was expected of Maraganore and his older brother and younger sister. “We were driven to do important things,” he recalls. If he got an A at school, his parents wanted to know why wasn’t it an A+. Get a B? God forbid. It was tough on Maraganore, because school didn’t come easy to him, as it does for some of those kids that can slack off and ace a test.
“They held you to high standards, and they were hard drivers. It was all around, ‘you need to do better, you need to work harder,’” he says of his parents. “I had to work like a dog. But it did create a real work ethic in me that I have to this day.”
While he sheepishly acknowledges a “Dungeons & Dragons” phase, Maraganore took on all sorts of additional extra-curricular tasks, like the chemistry club, chess club, and yearbook editor. He finished high school near the top of his class.
Maraganore’s father believed that being a doctor meant stability and a good life, and pushed his children towards medicine. The unspoken expectation, according to Maraganore, was that father and sons would open and run a clinic together. His father would bring things home from his lab for his kids, like a microscope that a young Maraganore became obsessed with. “Propaganda,” Maraganore jokes today.
Maraganore also remembers spending summers as an adolescent working in his father’s pathology lab testing patient samples. He learned a lot of lab basics—pipetting, what to do and not to do with blood—and performed radioimmunoassays (tests to measure, say, hormone levels in the blood) and serum chemistry tests.
“[That was] one of the great things about having a pathologist for a father,” Maraganore says. “It was just a great learning experience.”
Maraganore became a certifiable science geek. His favorite class was biology. He volunteered at his high school biology lab, staying late to set up experiments for the next day, or stocking and maintaining the lab’s saltwater fish tank. He’d visit Chicago’s Museum of Science and Industry and speed to the human biology exhibit. He’d collect water samples from different places and bring them to his microscope to look at paramecia or hydras.
“[I’d] look at the microscope, and sort of look at these little tiny organisms and so forth, or a slide and look at cells, and it’s just fascinating, right?” he says. “It’s so beautiful.”
Maraganore’s brother dutifully became a doctor (a neurologist). But Maraganore strayed from the prescribed path. In his sophomore year at the University of Chicago, intending to study medicine, he began doing basic research in a lab under biochemistry professor Bob Heinrikson. He purified and characterized proteins, specifically snake venom enzymes. He recalls being motivated by the idea of exploring things “nobody else in the world was exploring.”
“Just like I enjoyed it when I was a kid, looking at the microscope, I was doing it as an older kid in a basic research lab,” he says. He began to aim for a career as a university scientist.
He sped through grad school, also at the University of Chicago, getting his PhD in biochemistry in just two years, though he claims it was blind “luck” because of
