It happens over and over again with new science. A discovery prompts crazy hype and massive investment that the data aren’t ready to support. A crash ensues, backers lose millions, egos are bruised—yet the pioneers slowly trudge forward. They regroup, away from the limelight, and try to learn from failure.
When it comes to synthetic biology—a method of modifying the genes of living organisms to effectively change what they do—James Collins knows this story better than most. He’s an MIT professor who helped found the field nearly two decades ago. He’s seen the hype, when investors placed huge bets on startups aiming to produce clean energy on a large scale; the crash, when many of those companies were wiped out and scientists fled back to academia; and the pivot, when the surviving companies shifted their sights elsewhere.
“I think we’ve recovered now, as a field,” he says.
Gone are the days when a bevy of high-profile startups like Sapphire Energy, Solazyme, and J. Craig Venter’s LS9 offered hopes of renewable, eco-friendly fuels made by engineered algae. In their wake is diversification: Sapphire, for instance, has made a strategic pivot into things like food additives, cosmetics, and nutraceuticals. But from Collins’s vantage point, something else has happened. The “clinical space,” he says, has become a dominant focus for synthetic biologists—meaning tools that could be used for medical research, diagnostics, or even “living” therapeutics like the ones Cambridge, MA-based Synlogic, a startup from Collins’s lab, is trying to develop.
Collins (pictured above) is a New York-New England hybrid. He was born in the Bronx before moving first to Bellerose, in the outskirts of Queens, and later, after he finished elementary school, to New Hampshire. He used to have a strong New York accent and, as a Queens guy, was a fan of the Jets, Mets, and Nets. (Former Nets small forward William “Billy” Schaeffer, who also grew up in Bellerose, would shoot hoops nearby.) Now that Big Apple accent is largely gone (“I joke that I’ve got a New York attitude but not a New York accent,” he says) and Collins shows a fierce allegiance to all teams Boston. He even threw out the first pitch at a Red Sox game in 2008 at Fenway Park.
Collins’s mother was a math teacher; his father an engineer who worked with the aviation industry to develop an altimeter used in the Apollo 11. That naturally led him towards engineering, but biomedical engineering in particular became his passion after both of his grandfathers became disabled—one had a series of strokes, the other went blind. “While I saw this amazing technology that my dad would share with me on shooting stuff into and out of the sky, I was struck by the lack of technology to help restore function to these two guys that I cared for very much,” he says.
Collins graduated from Holy Cross in 1987 and afterwards became a Rhodes scholar who earned a doctorate in medical engineering from the University of Oxford. As a professor at Boston University in the ’90s, he worked to develop a “genetic toggle switch,” effectively launching the field of synthetic biology. By putting such a switch inside a cell, one could program it to sense and respond to elements in its environment.
The work was published in Nature in January 2000, and since that time, synthetic biology has undergone its ups and downs. That journey yielded important an lesson that Collins says he tries to teach his students at MIT, where he is a professor in the school’s bioengineering department. It’s a challenge that Collins says students aren’t well trained for: how to recover from failure. For Collins, the key is to move on quickly, and don’t dwell. “Did your paper get rejected? Well, send it to another journal. Did your grant get rejected? Well fine, get it to another funding agency,” he says. “Be hopeful that you’ve got another possible horizon to go after.”
This is the type of thing Collins has done for years. He claims to have failed “a lot” since starting out as a young academic at Boston University more than two decades ago. Despite winning of numerous scientific awards and a MacArthur fellowship, getting tapped by Eric Lander and Lee Hood to help with the Human Genome Project in the late ’90s, and being one of the more established company creators in synthetic biology—a few recent spinoffs from his lab include Synlogic, Sample6 Technologies, and EnBiotix—he’s keenly aware of what he can’t do.
Business skills, for instance, aren’t one of Collins’s strengths. When he started college at Holy Cross in the ’80s, he thought he might complement his engineering skills with business acumen. Along with friend (and later, Hollywood actor and writer) Mike O’Malley, he “devoured” a business book called In Search of Excellence, which centered on lessons learned from a number of successful companies. The pair was inspired and launched, of all things, a small company called Dance Warehouses, a dance club for kids too young to go to the bars. Safe to say the dream didn’t last. “We poured our heart and soul and much of our money into it and it failed miserably,” he says. “So I returned to campus thinking, business probably isn’t going to be the right spot for me.”
This is why Collins serves as a scientific advisor to his startups, rather than trying to shape their strategy. For example: Atlas Venture, a Boston biotech VC firm, was interested in the work Collins and postdoctoral student Timothy Lu were doing and arranged a meeting. The researchers showed the firm a few ideas, among them a technology for making therapeutic microbes, which grabbed Atlas’s interest and formed the foundation of Synlogic. Collins had been studying the use of these microbes to treat different bacterial infections, but Atlas decided to take Synlogic in a completely different direction. The company is now developing the microbes as treatments for rare metabolic disorders, where the medical need is greater, and the clinical trials are smaller and less costly.
“My forte is not translating a project into a product,” he says. “It’s on the front end of proof-of-concept experiments to validate and demonstrate what the cool new ideas are when they come up in the lab.”
I spoke with Collins recently about his strengths and weaknesses as a scientist and entrepreneur, the ups and downs of synthetic biology, and how to press on after your big idea gets shot down. Below are edited excerpts from our conversation.
Xconomy: So early on in college you try to start a dance company and fail. How’d you go from there to being a professor?
Jim Collins: I thought I might consider entering medicine, and unofficially joined the pre-med program at Holy Cross. I took organic chemistry and really loved it. But I did something quite smart, which was that I
