by Steven Prokesch
ONE MORNING LAST YEAR, James Dahlman came to Bob Langer’s office at MIT’s Koch Institute for Integrative Cancer Research to say good-bye. He was meeting with Langer and Dan Anderson—his doctoral advisers. The 29-year-old was about to take up his first faculty position, in the biomedical engineering department at Georgia Tech, and he wanted their advice.
“Do something that’s big,” Langer told him. “Do something that really can change the world rather than something incremental.”
These were not just inspirational words for a former student. They are the watchcry that has guided Langer, a chemical engineer and a pioneer in the fields of controlled-release drug delivery and tissue engineering, throughout his four-decade career at MIT. And they are part of the formula that has made Langer Lab one of the most productive research facilities in the world.
Academic, corporate, and government labs—indeed, anyone leading a group of highly talented people from disparate fields—could learn much from Langer’s model. He has a five-pronged approach to accelerating the pace of discoveries and ensuring that they make it out of academia and into the real world as products. It includes a focus on high-impact ideas, a process for crossing the proverbial “valley of death” between research and commercial development, methods for facilitating multidisciplinary collaboration, ways to make the constant turnover of researchers and the limited duration of project funding a plus, and a leadership style that balances freedom and support.
The United States alone spends roughly $500 billion a year on research, but “much of that is mundane,” says H. Kent Bowen, an emeritus professor at Harvard Business School who has spent years studying academic and corporate labs. “If there were more highly collaborative, Langer-like labs that focused on high-impact research, the United States would realize its enormous potential for creating wealth.”
Langer’s achievements are remarkable on several counts. His h-index score, a measure of the number of a scholar’s published papers and how often they have been cited, is 230—the highest of any engineer ever. His more than 1,100 current and pending patents have been licensed or sublicensed to some 300 pharmaceutical, chemical, biotechnology, and medical device companies, earning him the nickname “the Edison of medicine.” Alone or in collaboration, his lab has given rise to 40 companies, all but one of which are still in existence, either as independent entities or as part of acquiring companies. Collectively, they have an estimated market value of more than $23 billion—excluding Living Proof, a hair products company that Unilever is acquiring for an undisclosed sum.
A final “product” of the lab is people: Scores of the roughly 900 researchers who have earned graduate degrees or worked as postdocs at the lab have gone on to distinguished careers in academia, business, and venture capital. Fourteen have been inducted into the National Academy of Engineering, 12 into the National Academy of Medicine.
The multidisciplinary approach is still a work in progress in academia, but it has been gathering steam there over the past decade or so, reflecting universities’ growing interest in tackling real-world problems and spawning new businesses and a recognition that doing so often takes diverse expertise. Although it has long been common in the business world, companies too could improve their results by applying elements of Langer’s research-to-product process, thereby creating brand-new offerings and refreshing or reinventing their businesses again and again.
Focus on High-Impact Problems
One of Langer’s mantras when choosing projects is: Consider the potential impact on society, not the money. The idea is that if you create something that makes a major difference, the customers and the money will come. It’s a profound departure from the approach of many big companies: If an idea for a product is so radically new that discounted cash flow can’t be calculated, they often won’t pursue it, or they give up when the research hits an obstacle—as ambitious research almost always does.
To Langer, “impact” means the number of people an invention could help. The life sciences enterprises that have emerged from his lab have the potential to touch nearly 4.7 billion lives, according to Polaris Partners, a venture capital firm that has financed many of them. For example, one of the lab’s products, on the market since 1996, is a wafer that can be implanted in the brain to deliver chemotherapy directly to the site of a glioblastoma. Another, recently handed over to a new company—Sigilon, based in Cambridge, Massachusetts—is a potential cure for type 1 diabetes, developed in concert with researchers at other universities: Encasing beta cells in a polymer, the researchers have shown, can protect them from the body’s immune system yet allow them to detect the level of sugar in the blood and release the appropriate amounts of insulin.
With such concrete, ambitious projects on the lab’s docket, the customers have indeed come: foundations, companies, scientists in other labs, and government agencies including the National Institutes of Health. Foundations and companies currently fund 63% of the lab’s $17.3 million annual budget; they range from the Bill & Melinda Gates Foundation and the Prostate Cancer Foundation to Novo Nordisk and Hoffmann-La Roche. “A key reason we decided to work with Bob was his lab’s track record in controlled delivery,” says Dan Hartman, the director of integrated development and malaria at the Gates Foundation and the chief liaison between the foundation and the lab. “Bob and his team’s creativity and technical expertise cannot be overemphasized.”
A second criterion for project selection is fit with the lab’s core areas: drug delivery, drug development, tissue engineering, and biomaterials. “Most of what we do is at the interface of materials, biology, and medicine,” Langer says.
Third, he asks whether it’s realistic to believe that the medical and scientific challenges can be met by applying or expanding existing science, either at his lab alone or in collaboration with others.
This approach defies a long-prevailing view about the research-to-product process—that it is linear and looks like this: Basic research (endeavors aimed at expanding knowledge of nature, without thought of practical use) leads to applied, or translational, research (efforts to solve practical problems), which in turn leads to commercial development (turning discoveries into actual processes and products)—all culminating in a scale-up to mass production. The paradigm can be traced to Vannevar Bush, the head of the National Defense Research Committee and the U.S. Office of Scientific Research and Development during World War II and a leading proponent of strong government support for basic scientific research.
Since the war, universities have conducted the lion’s share of basic research, but corporations have participated too: Think of AT&T, Corning, DuPont, and IBM, to name just a few. In recent decades, though, big companies have come to see it as too expensive and risky: Results are slow and unpredictable, and capturing their value can be difficult. So they have increasingly turned to academia, sometimes buying or licensing discoveries or investing in or acquiring start-ups that develop them, other times funding academic research or having their scientists in academic labs.
However, the linear paradigm was never universally true. From the mid 19th century onward, great researchers have pushed the frontiers of basic science precisely to solve pressing societal problems. The Princeton political scientist Donald E. Stokes coined a term for the space in which they work: Pasteur’s quadrant, reflecting Louis Pasteur’s pursuit of a fundamental understanding of microbiology in order to combat disease and food spoilage. Other examples include Bell Labs, whose scientists made basic discoveries while improving and extending communications systems, and the U.S. Defense Advanced Research Projects Agency, or DARPA—one of the most successful innovation organizations ever.
Langer Lab resides in Pasteur’s quadrant too. Although its researchers devote the bulk of their efforts to applied science and engineering that could solve critical problems, in the process they often push the boundaries of basic science. For example, one of Langer’s most important discoveries was a way to release large-molecule drugs in the body via porous polymers at designated doses and times over several years. This involved expanding an area of physics and math known as percolation theory.
With some notable exceptions—Corning’s efforts in quantum communications and materials for capturing carbon dioxide, IBM’s in cognitive computing and smart cities, Alphabet’s in health care and self-driving vehicles—firms today aren’t striving to connect early-stage research with major real-world applications. “It’s very rare, but I don’t think it needs to be,” says Gary P. Pisano, a professor at Harvard Business School. “If you solve some of society’s big problems, you’ll actually make a lot of money.”
Susan Hockfield, a professor of neuroscience at the Koch Institute and a former president of MIT, agrees. “There’s a lot of appropriate concern and skepticism about the state of corporate R&D,” she says. “For example, pharma corporate R&D invests significantly in very early stage, exploratory research. Couldn’t they be doing better if they partnered more effectively with nonindustry biologists and engineers? And I just finished service on a commission to review the national labs. I’m astonished by what a brilliant idea they are and by the high quality of their research, but could they be turning more of their discoveries into products for the marketplace?”
Build a Bridge over the Valley of Death
Choosing the right projects to pursue is just the first step, of course; the path to realization can be long and treacherous. Langer has a formula for getting discoveries through the valley of death separating early-stage research and commercial development.
Focus mostly on “platform technologies”—those with multiple applications
Many corporate and academic labs look to solve specific problems without necessarily thinking beyond them. Langer Lab takes a broader view. In addition to creating a wider market, this strategy allows companies to pursue unanticipated applications, says Terry McGuire, a founding partner of Polaris. For example, Momenta, a company launched in 2001 to exploit new methods for understanding and manipulating the structures of sugar molecules, initially set out to sequence heparins in order to treat diseases such as cancer and acute coronary syndrome. However, it realized early on that it could also use the emerging technology to determine the complex structures in Lovenox, an existing multibillion-dollar drug. That work resulted in a biogeneric product for preventing and treating deep vein thrombosis, which generated more than $1 billion in sales during its first year.
Although the lab’s researchers often have a use in mind, sometimes they envision a variety of applications. For example, Langer got the idea for an implantable microchip that could release drugs for years and could be controlled outside the body while watching a television show on semiconductors; he imagined that chips could not only be used to deliver drugs but also put into TVs to release scents that would enhance the viewing experience.
Obtain a broad patent
MIT has been a pioneer in patenting and licensing academic discoveries. But Langer has been exceptional in his pursuit of especially strong patents. His goal is to limit, sometimes even block, others from claiming rights to the territory so that companies will be willing to expend the money needed to commercialize a discovery—an investment that must typically cover expensive clinical trials and that greatly exceeds the cost of the research. (Some of Langer’s secrets: Use “great lawyers” and have them challenge one another’s recommendations; eliminate unnecessary words that could restrict a claim; and clearly describe all the terms and supporting experimental tests to prevent ambiguity if the patent is litigated.)
Publish a seminal article in a prestigious journal
Appearing in a journal such as Nature or Science validates—and advertises—the soundness and importance of the discovery not just to other academics but also to potential business investors.
Prove the concept in animal studies, and don’t push the discovery out of the lab too quickly
The reason is twofold: to boost the odds that the discovery will work and to minimize the chances that commercialization efforts will flounder—a common occurrence in universities and even the corporate world.
One recent example of a project that benefited from a measured timetable involved the use of ultrasound to rapidly deliver a broad class of therapeutics, including small molecules, macromolecule biologics, and nucleic acids, directly to the gastrointestinal tract (they previously had to be injected). Despite promising initial results and the eagerness of one of the lab’s scientists to start a company to commercialize the discovery, Langer resisted taking that step just yet. He wanted to keep the lab team intact and to continue to work on the technology—for instance, demonstrating its safety through “chronic treatment” studies in large animals (giving them the treatment, say, daily for a month) and developing new formulations that could further enhance the delivery of the drugs.
This extra research, unfettered by commercial timetables, paid off. Over the next 18 months or so, the lab demonstrated that the technology could deliver a whole new class of drugs (unencapsulated nucleic acids), broadening its potential applications. The team also published more articles on the research in peer-reviewed journals, providing proof that the original data was reliable and replicable. Only then did Langer agree to help raise funds for a new company, Suono Bio, to take over development.
Reward the researchers
MIT awards inventors one-third of royalty income after expenses and fees. (The rest goes to the researchers’ departments or centers, MIT’s technology-licensing office, and the university’s general fund.) In recent decades a growing number of universities have instituted similar policies, but the approach is still highly unusual in the corporate world.
Involve the researchers in commercial development
Over the years many members of the lab have left for positions at companies that took on their projects, where their passion for getting the technology to market has proved as important as their expertise. “One of the reasons a lot of the companies have done well is that the champions have been our students who’ve gone to them,” Langer says. “They really believed in what they did in the lab and wanted to make it a reality.” Other researchers have advised companies while remaining at the lab or after moving on to other universities. Langer himself serves on the boards of 10 Boston-area start-ups that have emerged from his work. While a growing number of universities have relaxed restrictions on professors’ involving themselves in commercial ventures and have even encouraged commercialization by launching incubators and accelerators, there are still mixed feelings about such activities at many places that lack MIT’s established entrepreneurial culture. And in the corporate world, it’s highly unusual for scientists to become deeply involved in commercialization.
Make licenses contingent on using the technology
If a firm doesn’t make use of technology it has licensed from the lab, it can be made to relinquish the license. And consider how the wafer for treating brain tumors came to market: A company uninterested in the treatment happened to buy the firm that had licensed the technology. MIT got it to agree to launch a start-up to develop the wafer in return for a lower licensing fee. Few universities—or companies—manage their patents as aggressively as MIT does. Consequently, many of their potentially useful discoveries aren’t exploited.
Forge a Collaborative Multidisciplinary Team
A team working on an oral drug-delivery device that could sit in the stomach gradually releasing medicine for weeks or months came up with a star-shaped design. Then a mechanical engineer with modeling experience joined the effort and began to ask questions. Why had the team chosen a star? Why not other shapes? The team evaluated several possibilities, including hexagons and a variety of stars, and found that a six-pointed star performed best in terms of its ability to fit inside a capsule and stay in the stomach. The new team member also raised considerations about the stiffness of the arms and center, the strength of the elastomer at the interface, and the size of the unfolded device. This turned the conversation to materials that might enable the device to last longer.
“That’s what happens when you bring together folks with different backgrounds,” says Giovanni Traverso, a Harvard gastroenterologist, biomedical engineer, and MIT research affiliate who heads the team. “It leads to new insights and new ways of thinking about the problem.” The teams at Langer Lab include chemical, mechanical, and electrical engineers; molecular biologists; medical clinicians; veterinarians; materials scientists; physicists; and pharmaceutical chemists. Members from different disciplines sit side by side in the labs and offices that honeycomb the sixth floor of the Koch Institute.
Multidisciplinary labs are sprouting up as academia recognizes their value in tackling challenges ranging from cancer to global warming. (One of the hallmarks of the Stand Up to Cancer campaign is its funding of such teams.) But the revolution is still in early days. The 2016 MIT report “Convergence: The Future of Health,” coauthored by Susan Hockfield, highlights the importance of bringing together engineering, physical, computational, mathematical, and biomedical sciences “to help solve many of the world’s grand challenges.” It calls for ambitious reforms in education, industry, and government, including the creation of a “culture of convergence” in academia and industry and changes to government research-funding practices.
Langer’s reputation, the challenges his lab takes on, and the career opportunities afforded, including the chance to participate in start-ups, attract lots of applicants. The lab has 119 researchers from all over the world, plus 30 to 40 undergraduates each semester. It receives 4,000 to 5,000 applications for the 10 to 20 postdoc positions that open up each year and conducts global searches when specialized skills are needed for particular projects.
It’s a given that applicants must have outstanding academic credentials and be highly motivated. Beyond that, the leadership team of Langer, Traverso, and Ana Jaklenec, a biomedical engineer and MIT staff scientist, looks for people who “are nice, get along well with others, and are good communicators”—vital qualities given that the lab’s researchers must constantly explain their fields to coworkers and find ways to conduct experiments that work for everyone. Differences in technical languages, work practices, values, and even ways of defining problems constitute one of the most formidable challenges of a multidisciplinary lab, says Hockfield, a champion of convergence during her eight years at MIT’s helm.
Jaklenec showed me a whiteboard filled with equations. It was from a meeting of two postdocs—a biologist and a biomedical engineer who were collaborating on a single-injection polio vaccine that could stay in the body and be released in pulses over time. The biologist was exploring the mechanism that degrades the strain of virus used in the vaccine, while the biomedical engineer was working on thermostabilization. The two encountered a problem: Their data sets didn’t make sense together. It turned out that they had run their experiments with different concentrations of the vaccine: The engineer’s were those used clinically, while the biologist’s were those called for by the analytical methods of her field. The researchers had to align their experiments so that they could compare results. Such issues are not uncommon. “The challenge is to get people to talk the same language and also recognize that for certain things, there’s no single expert,” Traverso says.
Even if there is no obvious need or fit for them, Langer often brings in “superstars” who have unusual credentials. “You take a chance on people,” he says. “Gio is a good example.” Traverso had earned a PhD in molecular biology under Bert Vogelstein, a renowned cancer biologist at Johns Hopkins; his doctoral research involved novel molecular tests for the early detection of colon cancer. When he contacted Langer, he was finishing an internal medicine residency at Boston’s Brigham and Women’s Hospital and trying to figure out what to do with a gastroenterology fellowship he had landed at Massachusetts General Hospital. He told Langer that although he was interested in developing systems for delivering drugs in the GI tract, he was not an engineer. Langer hired him anyway.
The bet paid off. Traverso demonstrated the concept of several different approaches to delivering drugs through devices in the GI tract. The Gates Foundation saw that the work might solve problems it wanted to address in poor countries and provided significant funding. Grants also came in from Novo Nordisk (to develop microneedles for internal injections), the Charles Stark Draper Lab (for new ingestible systems), and Hoffmann-La Roche (for the delivery of a new class of drugs).
Embrace Turnover
Like all academic labs, Langer’s sees a constant flow of people joining or leaving. Doctoral students typically stay four or five years, postdocs two or three, and undergraduates participate for as little as a semester and as much as four years. Newcomers are perpetually being trained, and people may leave at the peak of their productivity. But Langer and many colleagues think the turnover has positives that vastly outweigh these downsides. Problems are viewed with fresh eyes—he calls it “constant stimulation.” The turnover is fairly predictable and tied to the length of projects; even huge grants are structured so that the lab can gradually scale up. The finite tenure of most of the researchers, combined with the limited duration of grants (typically three to five years, with renewals dependent on meeting goals), imposes pressure to get results.
“A lot of cynicism has been thrown on the academic research lab model. We are told it is inefficient,” Hockfield says. “But it’s brilliant. To bring together people from different generations and levels of experience—it’s fantastic. The faculty member has a wealth of experience and understanding and knows the literature and the history of the field. Students and postdocs have a lot of energy and ambition and crazy ideas. The faculty member helps get those crazy ideas channeled. Undergraduates, wonderfully, often don’t know that something’s impossible. They don’t know enough not to ask unsophisticated questions. There are very few things that make you step back and wonder about your foundational assumptions more than a really smart undergraduate asking, ‘Whoa, how does that work?’”
A highly motivated superstar team with limited tenure; an accomplished scientist leader; time-limited projects; intense pressure to get results—it all sounds like the DARPA formula, proof that the model has application far beyond academic settings.
Lead Without Micromanaging
One rainy day at their home on Cape Cod, Langer and his wife, Laura, talked about how his management of the lab differs from the norm. “In my discussions with a range of graduate students at other places, they often describe their research advisers as control freaks—which is understandable, because their lab is their baby,” said Laura, who has a PhD in neuroscience from MIT. “They may want to manage every part of the research. It’s very hard for them to let their students explore and make mistakes. But not giving people the room to figure things out themselves can stifle them or train them to not take potentially innovative risks.”
Langer nodded in agreement. Under his leadership, everyone is involved in offering ideas for projects and choosing which ones to pursue. “It’s a team effort,” he said. “It’s empowering people; it’s letting everybody feel they are valued and that it’s OK to suggest things.” This stands in contrast to most academic and corporate labs, where the director selects the projects.
Current and former lab members told me that Langer exposes people to possibilities and lets them decide what to work on. Gordana Vunjak-Novakovic, a professor of biomedical engineering and medical sciences at Columbia who worked at the lab in the 1980s and 1990s, says she took that lesson to heart and runs her 40-person lab the same way: “I never tell people what to do but, rather, help them see the possibilities, let them really get excited about one of them, and let them work on their own ideas.” Many if not most of Langer’s postdocs and research scientists and at least some of the doctoral students are working on several projects. (For a fuller picture of life in Langer Lab, see the profile of two postdocs in the online version of this article, at HBR.org.)
Langer treats Jaklenec and Traverso as coprincipal investigators—another departure from the norm. Power is distributed throughout the lab, accumulated on the basis of people’s ideas and initiative and the funding that their research attracts. Langer gives researchers—especially graduate students—lots of guidance in the beginning, to make sure that they get off to a good start and that projects are optimally structured. He also helps decide which options are considered. For example, at the outset of the project to develop the drug-delivery device that would stay in the stomach for a long period, he and Traverso decided to explore two possibilities: one that would float in the stomach and one that would adhere to the stomach wall. After conducting a feasibility study, they chose to pursue the floating option and figured out what major issues would need to be solved—and then Langer largely bowed out. “After that, I don’t tell people what to do,” he says. “From grade school to high school and college and even to a certain extent graduate school, you’re judged by how well you answer somebody else’s questions. That gives you a grade on a test. But if you think about the way you’re judged in life, I don’t think it is by how good your answers are; it’s by how good your questions are. I want to help people make that transition from giving good answers to asking good questions.”
Gary Pisano sees this philosophy as key to the lab’s success. “The tendency would be to say, ‘I’m going to tell you what to do so that you can do better and the lab will do better,’” he explains. “But if you do that, you create a different place—people are going to say, ‘OK, Bob, you tell me what to do.’ He doesn’t want that kind of lab. His lab is one where people solve their own problems, and that’s why they wind up being great professors and scientists in the business world.”
At the same time, Langer makes sure that researchers know they can count on him and on the people in his network if they run into trouble—an approach that Aimee L. Hamilton, an assistant professor of management at the University of Denver who has studied Langer Lab, calls “guided autonomy.” His responsiveness is legendary. His iPad seems glued to him, and he uses it to answer e-mails within minutes. Cato T. Laurencin, a University Professor at the University of Connecticut who earned his PhD under Langer in the 1980s, recalls that a student of his once dug up Langer’s cell phone number and called him with a question about a paper Langer had written. “He called her back from Finland 10 minutes later.”
Langer also goes out of his way to help people leaving his lab get good jobs, and he stays in touch with hundreds of alumni, providing assistance if needed. (In his farewell meeting with James Dahlman, he offered to go over Dahlman’s grant applications.) He is deeply connected to those in his network. For instance, he refers to many of the venture capitalists who have financed his start-ups—a group including Terry McGuire, of Polaris; Noubar Afeyan, of Flagship; and Mark Levin, of Third Rock—as friends, and means it. (Langer, McGuire, and their two daughters vacationed together last year in Bordeaux, and Langer’s daughter was in the wedding of McGuire’s.)
The investment in his network pays valuable dividends in the form of productive research collaborations, referrals of extraordinary students to his lab, and manpower for the start-ups. Langer not only paves the way for lab members to launch start-ups but also taps his network if a need at one emerges down the road. “Bob often has a great idea of somebody who would be a great fit,” says Amy Schulman, the CEO or executive chair of three companies that grew out of Langer Lab. “And people often reach out to Bob when they’re thinking of changing jobs, because he is incredibly discreet and knows a lot of opportunities. So it goes both ways.”
When people who have worked with Bob Langer talk about him, one hears a common refrain: He is an integral part of his research-to-product model and a brilliant individual who can’t be replicated. But this doesn’t mean that his model, including his “Mr. Nice Guy” leadership style, can’t be replicated. What if corporations structured their labs like his? What if they nurtured deep expertise in a handful of areas so that customers would come to them with their most pressing problems? What if they enticed superstar researchers by offering opportunities to work on issues that could change the world?
“Maybe companies could set up a research operation where the best of the best are flowing through, trying to do something audacious in a few years rather than spending 30 years there worrying about their next promotion,” Gary Pisano says. His Harvard colleague Willy Shih adds that such an approach would not only allow companies to tackle more-ambitious projects but also help them kill mediocre or poor projects faster. “The flow of people through the lab would have the natural consequence of sunsetting ideas that don’t stand the test of a fresh look,” he points out.
Bob Langer says, “I want to address problems that can change the world and make it a better place. That’s the thread throughout the science I’ve done my whole life. The companies I’ve helped found seem like a natural extension. I wanted to see what I did get out to the world; that made a difference to me.” By drawing on the Langer Lab values and model, companies could make the world a better place and make lots of money in the process.