The NEXT Next Big Thing

In December, Moderna Therapeutics announced that it had pioneered a technology that would revolutionize the practice of medicine and disrupt the pharmaceutical industry. But biotech startups have been making similar promises for decades, and the revolution has yet to arrive. Can Moderna really pull off what countless others have not?

By | Boston Magazine |

moderna team

Left: The Inventor, Derrick Rossi: A young professor at Harvard Medical School who specializes in stem cell research, Rossi in 2009 pioneered a new form of drug delivery that promises to make possible the targeted production of medicine inside the human body. Right: The Professor, Robert Langer: A world-renowned bioengineer at MIT with 25 startups under his belt, Langer immediately recognized the revolutionary potential of Rossi’s discovery. “It is very, very rare,” he says, “that an idea this big comes along.”

Rossi assigned Luigi Warren, one of his postdocs, to work on the task. About a year and a half later, in November 2009, Warren came running into Rossi’s office and exclaimed, “I think we got it!” Rossi raced over to the lab, looked into the microscope, and, to his delight, saw a plate full of IPS cells. He looked up from the microscope at Warren and smiled. “We did it,” he said.

Rossi was convinced that his breakthrough would make not just an academic splash but also a commercial one. As a relatively new hire at Harvard, with no previous experience as an entrepreneur, however, he needed advice. So he turned to his colleague Tim Springer, who had been successful in taking his discoveries to market. Rossi’s results greatly impressed Springer, who arranged for Rossi something that countless smart, young scientists can only dream of: an appointment with the venerable Robert Langer. “If you are going to start a biotech company in Boston,” Rossi says, “you go to Bob Langer.”


The operation that Langer runs out of his office at MIT is one of the largest academic bioengineering labs in the world. Langer has written more than 1,000 scientific papers and filed more than 800 patents for the discoveries made in that lab, which puts him up there, as one former student has put it, with the likes of Thomas Edison. One wall of his office is made completely of glass, affording him a sweeping view of MIT, where he has earned the distinction of serving as one of the university’s 11 elite Institute Professors. Another wall is covered with academic diplomas and honors, among them the Priestley Medal, the highest award conferred by the American Chemical Society, which Langer won last year.

But the reason that Langer’s inbox is flooded every day with emails from young scientists who want to meet him is that he has parlayed all of his smarts and breakthroughs into founding 25 companies, which make everything from cancer-drug delivery systems to hair gel. “It sounds like a lot,” he says, “but it’s been over 26 years. That is less than one a year.”

Langer is a very busy man. An entire feature in the weekly scientific journal Nature once chronicled the dizzying pace of a single day in his life, in which his printout of meetings for the day was three pages long, and during which he answered seven emails via his BlackBerry on a single trip to and from the bathroom. Most people on Langer’s calendar get 15 to 30 minutes with him, if they’re lucky. Langer gave Springer and Rossi two hours.

The meeting took place on an unseasonably warm day in late May 2010. Rossi and Springer crossed the river from Longwood, where they work, to the MIT campus for a 12:30 appointment with Langer in his office. The three of them gathered around a table, and Rossi pulled out his laptop and walked Langer through his data.

Rossi was not the first to try to insert mRNA into a cell to get it to express proteins. Others had tried, but without much success. That’s because when a cell senses that mRNA has entered it, it mounts an immune response that can result in the cell’s committing suicide rather than being overrun by the invader.

Rossi’s first breakthrough was to create a disguise for the mRNA so that it could slip into the cell unnoticed. As he explained to Langer, he did this by modifying two of the mRNA’s nucleotides, or building blocks. Once they breached the cells’ defense mechanism, the mRNA reprogrammed the cells into IPS cells. That was the feat that got Rossi so much acclaim. But what most struck Langer as he listened to Rossi was the first part: the technique that Rossi had developed to modify the mRNA. “This is a much bigger discovery than something that affects stem cell behavior,” Langer told Rossi, already imagining the potential. “You could apply it to make anything.”


Three days later, Rossi crossed the Charles again to make another presentation, this time at Flagship Ventures, at the very eastern end of Memorial Drive. Flagship not only invests in startups but also founds some of them itself, in a startup incubator it calls VentureLabs.

Noubar Afeyan is the CEO of Flagship. Born in Lebanon, and of Armenian heritage, Afeyan started in the industry in the 1980s, at MIT, where he completed a doctorate in biochemical engineering, a field that was emerging to meet the needs of the new biotech industry.

The dawn of that industry is typically dated to 1976 and the founding of Genentech, in the Bay Area. Six years later, the company’s first biotechnology drug, genetically engineered human insulin, made with recombinant-DNA technology, won FDA approval. (Until that time, insulin was derived from cows and pigs.) When Afeyan was in grad school, Genentech was still a young company, and the Boston-based Genzyme was tiny. (It’s now one of the world’s biggest biotech companies, acquired in 2011 by Sanofi for $20 billion.)

What the industry lacked in size in those days, it more than made up for in perceived potential, poised for spectacular growth and wholesale improvement of human health. And in the decades that followed, new technologies (and startups) emerged that promised to revolutionize therapeutics. There was gene therapy, which involved replacing a faulty gene with a normal one. There was the sequencing of the human genome, which promised to speed drug discovery and personalize medicine. Most recently, there were antisense therapy and RNA interference, which used other kinds of RNA to block cell activity. All have been touted as the next big breakthrough in biotech, but none has produced a revolution in the industry, or much in the way of new drugs.

Having lived through all this, Noubar Afeyan is not one to get overly excited about the pitches that come his way. But when Rossi approached him with his idea, Afeyan immediately sensed it represented a major development. Like Langer, he recognized that Rossi’s achievement amounted to something far greater than simply the creation of IPS cells. (Rossi insists that he, too, saw the therapeutic potential, although Langer and Afeyan recall he was more interested in the stem cell potential of his technology.) What most captivated him was the possibility that Rossi’s technology might make possible an entirely new way of making drugs—inside patients’ bodies.