On Taking Risks and Thinking Big
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Dr. Robert Langer is the David H. Koch Institute Professor at MIT. He has over 1,250 articles, 1,050 patents, and 220 major awards to his name, most recently Japan’s Kyoto Prize. He is widely regarded as one of the founders of tissue engineering.
Methuselah Foundation: What’s your perspective on the current state of tissue engineering?
Robert Langer: Well, a lot of progress has been made, and there’s still a lot to do. We did some of the early studies in the 1980s with Joseph Vacanti, and I’m very pleased to see how far we’ve come and how many people are working in the field today. Overall, I think things have gone very well.
MF: What do you see as some of the key present challenges, especially with respect to the Holy Grail of regenerating or bioengineering whole organs?
Langer: It depends on what method you use, but some of the biggest concerns are cell death, vascularization, innervation, and rejection. From a practical standpoint, there are others as well—cell expansion, cryopreservation, and so on. Then there are particular issues with each individual tissue or organ you’re trying to do. And beyond the science, you’ve got regulatory challenges, manufacturing challenges, legal challenges . . . . There are plenty of roadblocks.
MF: In your mind, what is the most promising work going on these days in tissue engineering?
Langer: I think there’s a lot of it—everything from IPS cells to stem cells to new materials. There’s a lot of very good basic and applied work going on. People are trying to understand and design bioreactors, factors that affect cell growth, new kinds of biomaterials, decellularized constructs. There are all kinds of animal and clinical trials going on. And then in each particular area, I think there’s been exciting work—skin, lung, eyes, kidneys, pancreas, vocal cords, spinal cords, etc. There’s just a tremendous amount of good work being done.
MF: Would you say this field has one foot in basic science and one foot in applied science, or are both feet mostly in the applied science domain, where it’s more about, time, money, and the translation of existing knowledge?
Langer: I think it’s both. It depends on how you define it, but I see both basic science and applied science as being important, and I think they have been from the beginning. Sometimes it’s not so obvious that one is doing something for a particular goal. Work that people may do in areas like embryogenesis may be very useful for regenerative medicine, but it may not be the intent of the people who are doing that work to apply it that way.
MF: What do you think about the state of cross-institutional collaboration in tissue engineering and regenerative medicine? Is it strong enough?
Langer: I think it’s pretty good. At least, I don’t think it’s a big roadblock. We collaborate, for example, with many hospitals like Mass General. I mentioned Dr. Vacanti in tissue engineering and also Dr. Zeitels in tissue engineering. We collaborate with the Brigham, we collaborate with Johns Hopkins, we collaborate with lots of places, and we collaborate with companies too. Whatever is going to advance the science, I’m absolutely in support of.
MF: You’ve founded and been involved with a lot of biotech companies. What have been the biggest challenges to success, especially in the U.S.?
Langer: The key is raising money, because it’s just so incredibly expensive. I think they estimate now that it costs well over a billion dollars to create a new drug. So raising money is crucial. You also have to have mitigation strategies for things that don’t work out. You don’t get that many shots on goal. Doing good science and having good intellectual property are the foundation, but anything in the medical area is a very, very expensive proposition. It’s not like the internet.
MF: How do you feel about the state of IP in biomedical engineering? Is it sufficient?
Langer: I think it’s okay. One of the problems is that when you do things that are highly advanced, you only have finite lifetimes. Vacanti and I filed some patents in 1986, for example, that have expired by now, and those are very broad patents. You’d think that 20 or 21 years was a long time, but when the research takes so long, then by the time actual products come out, it’s not such a long time.
MF: Are you happy with the amount of funding that tissue engineering is receiving?
Langer: No, I think it needs a lot more. To me that’s a huge issue.
MF: How do we change that situation?
Langer: Well, it’s very hard. For example, I think what you’re doing with New Organ is great, but you’re doing it on the back end, and the problem is that we need more funding on the front end. Government grants are really the key, and it’s very hard to get them. And I’m not limiting it to this area. Barack Obama asked me about stem cell research for his book, The Audacity of Hope, and I said to him that it’s really important and it would be great if there were more funding. But the fact is, there are hundreds of areas of research for which you’d like to have more funding. They’re all getting hit. That was true when I talked to him in 2006, and it’s even more true today.
MF: Do you have a sense of the scope of funding that the NIH is providing right now for tissue engineering and related work?
Langer: I don’t know all the grants that are given and spread across the many different institutes of the NIH, but I know a lot of people, including us, that have grants from NIH funding basic work in stem cells. We’ve gotten grants in different biopolymer work, intestinal research, craniofacial research. I think they’re quite diverse. But the question is: If they only fund 5% or 10% of all the grants they receive, that means there’s going to be a lot of good grants that don’t get funded. The overall problem is the limited amount of funds for medical research, period. And in particular, what happens when money is tight is that really long-range projects don’t get funded at all. Projects that are being done by younger researchers are often not funded, as well.
MF: The philanthropic sector seems to be underfunding these areas as well, and has been for some time.
Langer: I think that’s probably fair. I would agree with that.
MF: Why do you think that is? For example, when I look at the Giving Pledge signers list—100 plus billionaires committing 50% or more of their networth toward charity—it’s hard to find many of them who are allocating funds toward tissue engineering or regenerative medicine.
Langer: I think people do things on a fairly disease-specific basis. Cancer and heart disease are still the number one killers, and people usually support things they’ve seen close relatives die from.
MF: That seems right. Let’s talk a little bit about your lab, which has a tremendous reputation and a prolific level of output. What do you think makes it so special?
Langer: Well, our lab is very interdisciplinary. Our people have backgrounds in many different areas—MD’s, chemical engineers, material scientists—and they are all bright and self-driven. I see it as a training ground for people to become future leaders, inventors, and scholars.
MF: In developing New Organ, we’ve had more conversations with people saying that they came out of your lab than anywhere else.
Langer: Yeah, that might well be.
MF: Looking back over your career, what do you think are some of the main factors that have enabled you to build such a significant, collaborative network that has been so productive over the years?
Langer: I like to think it’s treating people well. It’s thinking out of the box. It’s trying to go after big problems. Those kinds of things.
MF: If one of your students told you they wanted to follow your example and aspired to reach a similar level of accomplishment in his or her career, what advice would you give them?
Langer: Well, I think when you’re young, it’s best to learn the fundamentals well. Learn a single discipline well. When you get a little older, like for your postdoc, maybe then it’s good to really learn something different. I’m a risk taker. I dream big dreams, and I am very, very persistent. I don’t give up easily. I get discouraged, but I’ll keep plugging along. And my goal has been not just to come up with ideas on the blackboard, but to take them all the way to the patient, to make a difference in peoples’ lives.
MF: Were you more of a risk taker from the beginning, compared to your colleagues?
Langer: Yes, I guess I was. My postdoctoral advisor Judah Folkman was somewhat like that. He took risks, and I think seeing that example was very helpful to me. I think I was probably also lucky. I had a postdoctoral opportunity that put me on an interesting path as the only engineer working in a hospital, and that’s what got me started. It gave me a lot of ideas, and I began to approach things in a different way than others would.
MF: What kind of research is being pursued presently in your lab?
Langer: On tissue engineering, we are working on a range of things—new pancreas, new intestines, spinal cord repair, nerve regeneration. One particular hope has been to design more highly super-biocompatible polymers. But we’re also doing work that is more basic, such as trying to understand how stem cells can be affected by materials in terms of their growth and their differentiation.
We’re also working on things that are indirectly related to tissue engineering, such as: Could we deliver genetic information like siRNA, or mRNA, or DNA to cells to change their character? We’re looking at ways of doing controlled release of different proteins that could modify the cellular environment. So it’s broad based. There’s also a lot of work that is less related to tissue engineering, like work involving drug delivery and new materials.
MF: I’d be curious to hear more about the work on the pancreas.
Langer: Well, the key to it is cell encapsulation. The capsules that protect the cells get encapsulated themselves with fibrous tissue, and that’s a problem. So we’ve been working with Dan Anderson, who is a professor at MIT and one of my former postdocs, to develop what are called high-throughput strategies to synthesize literally thousands of polymers and find ones we can make that are super-biocompatible.
MF: How much have you invested so far into that line of work to get where you are, and how long has the work been underway?
Langer: Six years, and I’d have to check, but it’s probably $6 to $10 million.
MF: Switching gears, what do you think are some of the most compelling reasons to support the case that tissue engineering and regenerative medicine should be a greater priority in society?
Langer: The way that I look at it is that drugs are only going to be able to treat so much, right? Drugs are not going to be able to treat people that are dying of liver failure or heart failure or many other things. To me, tissue engineering is a whole new paradigm for which there really is no substitute. It will change the world in a major way.
MF: Are there other things we could be working toward through New Organ to help advance the field?
Langer: I don’t know the right way to do it, but if we had a Human Genome Project-type effort at the federal level, that would be tremendous. I think tissue engineering is ready for a similar kind of effort to drive the field forward.
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