Tom Maeder, Senior Editor, MedTech Intelligence

Making Translational Engineering Work: A Conversation with MIT’s Robert Langer

By Thomas Maeder
Tom Maeder, Senior Editor, MedTech Intelligence

For the past decade “translational science” and “translational medicine” have been cherished buzzwords, raising the prospect of faster, better, more seamless transfer of discoveries from bench to bedside. Too often, though, it doesn’t work. Differences in the cultures of academia and medical manufacturing, and a poor grasp of regulatory and reimbursement issues, or of what makes a bright idea into a clinically useful, commercially viable product have scuttled more than one promising innovation.

A notable exception is the prodigiously productive lab of Robert Langer at the Massachusetts Institute of Technology, which has spawned over a dozen companies, some of them successful standalones, others subsequently acquired by larger corporations, including Advanced Inhalation Research, MicroCHIPS, Alkermes, Transform Pharmaceuticals, Acusphere, Nova Pharmaceutical, Focal, Momenta, Noemorphics, EnzyMed, Reprogenesis, Sontra Medical, MnemoScience, Pulmatrix, and Pervasis Therapeutics.

MIT Professor Langer’s four basic requirements for a combined clinically-useful and commercially-successful idea: “You want a platform technology. You want a powerful blocking patent so that you own the space. You want to write a seminal paper in a top journal. And you want to prove the concept in an animal model.”

MIT Prof Langer’s four basic requirements for a combined clinically-useful and commercially-successful idea: “You want a platform technology. You want a powerful blocking patent so that you own the space. You want to write a seminal paper in a top journal. And you want to prove the concept in an animal model.”

Langer himself embarrasses us mere mortals who muddle through life doing one thing at a time. His current CV lists over 1100 papers, 13 books, three course texts, 769 U.S. and foreign issued or pending patents that have been licensed by more than 200 companies, positions on 39 editorial boards, and a dizzying array of honorary degrees and other awards including the Charles Stark Draper Award (engineering’s equivalent to the Nobel Prize), the U.S. National Medal of Science, the 2008 Millennium Technology Prize (the largest technology prize in the world), and induction into all three major national science academies – the Academy of Sciences, Academy of Engineering, and Institute of Medicine. A cover story in the Boston Globe Magazine dubbed him “the smartest man in Boston,” a town known for brainy people. In 2006 he threw the ceremonial first pitch in front of 35,000 Red Sox fans at Fenway Park – a strike.

Driven by scientific curiosity

Langer does not fit the stereotypical image of the driven, Type A entrepreneur, and the secret to his success is disarmingly simple, at least in principle if not in execution. What drives him is not money, but scientific curiosity, a desire to make beneficial contributions, and a yearning to bring together disparate disciplines to meet important medical challenges. Some of his comments seem counterintuitive when speaking of the commercialization of technology: “It is more important to do deals than to make money. Making money is not the real criterion. You want impact.  Everything else follows.”

At the dawn of his career Langer, then a freshly-minted MIT chemical engineer, turned down potentially lucrative but boring job offers from the petroleum industry, and instead applied for position at medical schools, which in the early 1970s did not embrace engineers. He ended up in the Harvard lab of Dr. Judah Folkman, who was then wrestling with practical applications of his bold thesis that the key to fighting cancers was the use of anti-angiogenic agents to counteract tumors’ ability to promote the proliferation of new blood vessels to support their own growth. Finding suitable agents was one challenge. Langer’s problem was designing materials capable of delivering these agents with the appropriate kinetics.

Medicine was an area ripe for innovation in the early 1970s. At that time, investigators still tended to scrounge among materials at hand to meet their needs – ladies’ girdle fabric in an artificial heart, breast implants filled with mattress stuffing – and turned a skeptical eye to a chemical engineer and materials scientist with no real medical training who presumed to change their field. But ingenuity and persistence prevailed, and Langer was gratified by the tremendous difference he was able to make. He was able to custom design porous plastics with the drug release properties Folkman’s work needed.

Turning an idea into a product that is widely available to benefit patients requires a grasp of real world issues beyond the walls of academia, something that in the years before the biotech revolution was more familiar to engineers than to medical practitioners. “Industry is key to getting products out the door and to the public. We can develop an idea and get a patent, but you need the industry to help develop the products and manufacture them.” Academia, however, has not always looked fondly on industry or applied science, though if handled responsibly and ethically, collaborations can yield tremendous benefits for both without compromising the interests of either.

Driving industry relationship from within academia

The relationship, to be successful, needs to be driven from the top within an academic institution, not simply from a business or technology transfer office. “The two regions that are best at creating small companies are Boston and San Francisco. I don’t think it’s a coincidence that Harvard and MIT are in one and Stanford in the other. You have outstanding universities in many other places as well. The difference is having people at those universities who have tried to create cultures of entrepreneurism.”

Langer points to the example of Fred Terman, a Stanford electrical engineer, often called the “father of Silicon Valley,” who in 1937, encouraged former students William Hewlett and David Packard to launch their company in Palo Alto and maintain strong ties with the University. Over subsequent decades, Terman, as provost and university vice president, and Stanford recruited, encouraged, supported, and partnered with the founders of numerous innovative and highly successful companies, and helped form the first high technology industrial park as a nourishing incubator for the practical development of original scientific discoveries.

Creating a win-win-win situation

“Tech transfer offices can be helpful,” Langer says, “but what you really need is leadership at the president and provost level.” He works closely with the tech transfer office at MIT, which he thinks possesses the seemingly obvious but often absent understanding of how to create a win-win-win situation for the founding scientist, university and companies. These three stakeholders come from dramatically different perspectives, may have divergent objectives, yet each should feel appropriately rewarded by the success of a collaborative venture.

“You need to understand where each group comes from, and what academics are and aren’t good at. We can make discoveries and inventions, but you can’t invent on a timeline. And academics, on their side, need to understand that they can’t know or do everything.  There’s a role for very basic research, and one for applied research.  It’s a team effort with people from many disciplines.”

One of Langer’s early ventures became the Gliadel Implant Wafer, an implantable, biodegradable polymer disk that delivered a chemotherapeutic agent directly to post-surgical brain tumor sites. Developed by Langer with Johns Hopkins neurosurgeon and former Folkman lab colleague Henry Brem, the wafer showed clinical potential, but roused little commercial interest because the 14,000 target patient population did not justify the financial investment and risk. They succeeded in taking the product to the market by reducing their own and their universities’ royalties to nothing.

Addressing high-impact problems

The choice of high impact problems whose solution will change the world is linked to Langer’s ethical and socially responsible nature, though, happily, beneficially disruptive discoveries are also often those that lead, either immediately or farther down the road, to the elaboration of a commercially viable new field.

University tech transfer offices vary in their knowledge and skill, often overestimating the value of basic discoveries, or underestimating the type of work and evidence needed to convince venture capitalists or companies interested in licensing agreements of the idea’s commercial viability. Langer boils the basic requirements down into four elements, with the caveat that rules can always be bent. “You want a platform technology. You want a powerful blocking patent so that you own the space. You want to write a seminal paper in a top journal. And you want to prove the concept in an animal model.”

What happens with a discovery depends on the idea and the people involved. A one-shot innovation might be licensed to an existing company, while a platform technology may be grounds for the founding of a new one. Some scientists are happiest in academia and gladly watch with paternalistic pride as their discoveries go into the world on their own, while others want to guide their innovations through to the end.

Of those researchers who left the Langer lab between 1979 and 2003, according to a 2006 Harvard Business School study on the Langer lab model of commercializing science, 46 percent stayed in academia, 42 percent went into the corporate world, and 12 percent pursued medical careers. Some who were responsible for discoveries that turned into products chose to remain in basic academic research, following the companies and products born of their ideas from a distance or through advisory board participation.

“There are different kinds of people and they need to recognize what they want to do and what they are good at. Some approach things narrowly. Others, like John Santini, approach things differently.”

Santini began working with Langer and Michael Cima, an MIT materials scientist, as a summer intern while still an undergraduate at the University of Michigan. He returned as a graduate student to develop a microprocessor-controlled drug delivery system that led to the founding of MicroCHIPS in 1999, with Santini as the president and CEO, a position he recently left to start a new spinout ophthalmic drug delivery company.

The real key to Langer’s success, and the feature hardest to replicate is the types of nurturing relationships he cultivates with students, the university and its technology transfer office, venture capitalists, and corporate America.

“My lab people are almost like my children.  I’m still in touch with almost everyone who has been in my lab.” And Langer’s is a very large lab, with over 80 graduate students, post-docs, visiting researchers, and assistants. “What you want to do is to show people to believe in themselves, that almost everything is possible.  Follow your dreams.  I really believe in that.”

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Tom Maeder, MedTech Intelligence