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Lemelson Winner Discusses Innovation, Education


Thomas E. Murphy--The Tech
Robert S. Langer ScD '74 discussed science and education with The Tech last week. He was recently named the first MIT-affiliated winner of the $500,000 MIT-Lemelson prize for innovation.

By Aileen Tang
Staff REPORTER

Robert S. Langer ScD '74, the Germeshausen Professor of Chemical and Biomedical Engineering at MIT, was recently named the 1998 recipient of the $500,000 Lemelson-MIT Prize, the world's largest single prize for invention and innovation. Established by the late prolific inventor Jerome H. Lemelson and his wife Dorothy, and administered by MIT, the award is presented annually to an American inventor-innovator for outstanding inventiveness and creativity.

The first MIT-affiliate to receive the Lemelson-MIT Prize, Langer's pioneering research with polymers has led to a majority of his discoveries and earned him the Lemelson-MITdistinction. His achievements resulted in many breakthroughs, including brain cancer treatment, tissue repair, innovative waste disposal, and controlled drug delivery, which benefits millions of people each year.

Langer received a Bachelor of Science with Distinction in Chemical Engineering from Cornell University and a Doctor of Science in Chemical Engineering from MIT, where he has been teaching and doing research since 1977. He is currently the holder of 320 patents, author of 550 research papers, editor of 12 books, and the recipient of over 60 national and international honors.

Last week, The Techsat down with Langer to discuss his accomplishments, his research and his history as a scientist and inventor.

The Tech: Professor Langer, what initially inspired you to become interested in chemistry and chemical engineering?

Robert S. Langer:When I was a little boy, I was given a Gilbert chemistry set and I was really excited playing with it, making bubbles and seeing colors change in response to different chemicals. I suppose that was the very first time when I got interested in chemistry.

Tech: How did your interest persist?

Langer:When I was in high school, I took a chemistry class and I enjoyed that too, probably for the same reasons. In college, I enjoyed chemistry, and I actually didn't enjoy some of the other courses. Since I was in an engineering school, I thought chemical engineering was an interesting area to go into, so I studied that as an undergraduate, and again in graduate school.

Tech: Why did you choose to enter chemical engineering over chemistry?

Langer:One of the things that's been very important to me is to do some good basic work, but I also want to see it go some place and help people. I write scientific papers, and some of that work is pretty basic, but I like to do it in the context where a real life problem may be solved, or has the potential to be solved.

Polymers prove to be useful

Tech: In much of your work, one discovery often led to the development of another, particularly with the research involving polymers, which earned you the Lemelson-MIT Prize. In what ways have polymers played an important role in your researches on tissue regeneration and controlled drug delivery?

Langer:When you make a discovery, it also leads to a lot of unanswered questions. When we first showed that you could use polymers to slowly release large molecules, people were pretty skeptical that you could do it. Then a couple of years later, people in some other groups reproduced it, and then everybody kept asking "Well how could this possibly work? What's the mechanism?" And then a couple years after that, after we identified the mechanism, one of the issues was how stable would these large molecules be? So Alex Klibanov, a Professor of Chemistry, and I decided we'd study that.

In other words, each time you solved a problem, it's not like you solved everything. It's a long long way from a concept to the clinic. We often raise more questions than we answer.

Tech: What characteristics of polymers actually allow you to apply it to so many areas?

Langer:There are many great things about polymers, particularly synthetic polymers, which are used in so many aspects of our lives. The beauty of synthetic polymers is that you can tailor them to do both chemically and physically almost anything you want. So chemically, you can tailor them to give the exact degradation rate. You can make them last for a day, or you can make them last for a year. You can also impart other properties, like mechanical strength. Physically, you can control the pore structures of these very precisely, and that is very important for controlling the release rate of a particular drug. In dealing with synthetic polymers, there are synthetic challenges, and some there are processing challenges, but you have the ability to ultimately make polymers that can do what you want in many cases.

Tech: Can you pin-point one idea that initially sparked the decision to use polymers?

Langer:I had worked at a hospital for a number of years, and one of the things I noticed in the hospital is how materials began to get used in medicine. I would've liked to have thought that material scientists or chemists or chemical engineers played the central roles. That actually wasn't the case. Before we got involved, clinicians took off-the-shelf polymers used in a household object, and said basically, "If it resembles the organ we're trying to fix, then use it in medicine." For example, back in 1967 when clinicians wanted to make an artificial heart, they wanted an object that had good flexural properties and decided to use a ladies' girdle. Then they asked, "What's the material in a ladies' girdle?" It's a polyether urethane, so they made the artificial heart out of that. Some of the problems with the artificial heart is that some blood exposed to its surface forms a clot, and the patient can get a stroke.

Actually, if you look at almost all polymers that are used in medicine today, they had similar origins. Like the breast implants, one of them was originally a lubricant, another was a mattress stuffing. So I started approaching the problem like an engineering design project.

Tech: And create your own materials?

Langer:Yes, so I started thinking, "Well why don't we ask what you really want in a biomedical polymer," from an engineering standpoint, from a chemistry standpoint, from a biology standpoint, and we put all these down on paper and asked different engineering design questions. Then we synthesize the material. So that's really the way we got started.

Tech: What are some specific examples of when this idea was applied?

Langer:In the late 70's, we were incredibly limited, and we still are, in terms of the number of synthetic degradable polymers that you can use in a person. The only type of synthetic degradable polymers were polyester sutures. They were okay for some things, and we've used them for some delivery purposes. But they also show a property called "bulk erosion," meaning that over time, they become spongy they and ultimately fall apart. So if you uniformly distribute the drug in the polymer, it could potentially dump the drug.

Asking from an engineering standpoint, "What would be ideal for drug delivery," we decided you wanted what we call "surface erosion," which is analogous to the way a soap dissolves. The challenge was, could we make a polymer that would show surface erosion? We came up with the idea that a family of polymers called polyanhydrides could do this, and got to that point by asking a lot of engineering design questions. Then we synthesized these polymers. There were a number of synthetic challenges, but we were able to solve them and now we can make the polymers last anywhere from a day to six years or anytime in between.

One of the areas that surface eroding polymers can be applied is in the treatment for brain cancer. Henry Brem, a colleague of mine at Johns Hopkins, and I started thinking, "What if we were able to make a polymer that would just slowly release a cancer drug right to the tumor?" And it's important that its through surface erosion because you wouldn't want to dump a bad drug like that into the brain. From other studies we did, we wanted the polymer to last for four weeks, so we made a brain cancer delivery system out of these polymers.

So now when a neurosurgeon operates on a patient, they take as much tumor out as possible, and before they close up the patient, they put in little wafers, each a little smaller than a dime, into the brain. The whole idea is that this gives you a way to locally deliver the drug to a tumor, and it's also better from a chemotherapy standpoint because you don't have all the toxic side effects associated with getting these drugs intravenously.

Tech: Are there any side effects at all?

Langer:Much fewer than systemic chemotherapy. In fact, when I got the award, a patient who was treated by this technique came to the ceremony. He said that there were no side effects, and he is now still alive and well a number of years later. Basically he went in, had the operation, and was back to school within a week.

Solving drug delivery problems

Tech: What is involved in your research on controlled drug delivery?

Langer:In controlled drug delivery, we work today on mainly two types of approaches. Approach one is we create materials that can solve drug delivery problems. An example of that is before our research, scientists could only slowly release low molecular weight lipophilic drugs such as steroids. We created approaches using synthetic polymers to deliver drugs of all molecular weights, including high molecular weight drugs like peptides, proteins and DNA.

A subset of this research is work we're doing with Professor of Chemistry Alexander M. Klibanov to stabilize proteins. For example, when you're trying to release proteins for a month, these molecules may become unstable in the presence of water and body temperature. We are also developing microchips with Professor of Materials Science Michael J. Cima so that someday you could have a whole pharmacy on a chip. Another area of research is to synthesize polymers that display surface erosion. These are now used in the treatment of brain cancer.

The second aspect of our controlled drug delivery research is transport: Can we develop approaches so that you don't have to take injections? First, could you deliver complex molecules through the skin? Right now you can deliver a couple of molecules through the skin. All of these are lipophilic, such as nicotine and nitroglycerin. I'm working with Visiting Professor Joseph Kost and Professor of Chemical Engineering Daniel Blankschtein, to see if we can use ultrasound to deliver different molecules. I'm also working with Dr. James C. Weaver of Health Sciences and Technology to see if we can use electricity. We've also done work with Dr. David Edwards to create new aerosols whereby you can inhale complex molecules like proteins or DNA. We made the aerosols resemble whiffle balls to give them a much lower density but higher diameter than conventional aerosols, which might look like small golf balls. This way, the aerosols don't aggregate nearly the same amount and will flow into the deep lung because of the differences in aerodynamics and be absorbed more easily. We've also done work with Richard Mulligan at Harvard Medical School developing new approaches for gene therapy, using novel synthetic polymers as carriers for DNA.

Tech: Is one method easier to incorporate the drug into the body?

Langer:It all depends on the type of drug. If you have a simple molecule, like an aspirin, then your goal is to swallow it. If on the other hand, it is a complex molecule, like a protein or a peptide, then you probably need to inject them. Many of those peptides don't last very long, so you might need to put it in a plastic microcapsule that you can inject underneath the skin, and have it release for a long time.

Discovering tissue regeneration

Tech: Your other major research area is tissue regeneration. Can you talk about that?

Langer:The tissue regeneration research started in the early 1980's in collaboration with Jay Vacanti, a professor at Harvard Medical. He is in charge of organ transplantation at Children's Hospital. We've known each other for a long time. He performs transplants on children with liver failure. We started talking: "Could we ever come up with strategies to actually make a liver or any tissue from scratch? Could we take the patient's own cells or a close relative's cells and make a tissue from them? Could we also develop an approach of using synthetic polymers that would enable you to do this?" So it really came through clinical needs that Jay had and from the polymer and bioengineering background I had.

Tech: Interestingly, one of the areas to which your research is applied is in innovative waste disposal. Can you describe what that is?

Langer:Years ago, one of my post docs was trying to synthesize certain polymers, and our goal was not necessarily to use it for innovative waste disposal. Our goal was to have it be able to bind to certain chemicals in the body, but there was a company that decided to license it. It was done through the Technology Transfer Office. The company thought that the polymer could also bind to certain wastes and make them easier to separate out, so they licensed it for that. It's now used pretty widely as a flocculent.

That's again an example of when you develop a broad based technology or material with an initial idea about what it's going to be used for, but once you publish it, lots of other people see it, and they may take it into new areas.

Overcoming obstacles in research

Tech: Do you believe an important part of being a scientist is being able to defend your work? How did you overcome obstacles in your research?

Langer:There's always a lot of obstacles. In 1981, people reviewed our ideas and said, "You can never synthesize these polymers." Two years later, after we synthesized these polymers, they would ask, "Won't these polymers react with drugs?" Two years after that they said, "Even though you've solved that problem, the polymers are very fragile." And this was true, because at that time we had made only low molecular weight polymers. It took a lot of work, but one of my post docs, Avi Domb, then synthesized high molecular weight polymers.

We overcome obstacles first by being very stubborn and persistent, and really believing in what we're doing. Of course the only way you ultimately defend your work is with more science. Secondly, one of the greatest things about MIT is that I have enormously talented students and post docs, and you give them projects like, "Can you develop a way to make sure that these polymers don't react with the drugs?" "Can you synthesize a polymer that's high molecular weight?" This might be an entire thesis or several theses until we solve them. So it takes being very very persistent and working with great people.

Tech: Some say that research is like trying to reach the other end of a pitch dark tunnel, where you may not know where the current path leads you. Have you felt that way about your research?

Langer:Sometimes. M. Judah Folkman of the Children's Hospital was my post doc advisor. He once said that doing research is like driving a car at night. You're making a long trip and you can't see beyond your headlights, but you can make the whole trip that way. I think there's a lot of truth in that. You have an idea of where you want to go, but there area many problems and each has to be solved.

In developing these degradable polymers, I had no idea when we started it in 1980 that it would lead to the treatment of brain cancer. That happened by developing what I call an "enabling technology." Once a problem is solved, other people see it, in this case Dr. Brem from Johns Hopkins, and they get ideas to apply the solution to other areas. That's the beauty of how science works.

Tech: As a scientist and inventor, do you see world differently?

Langer: Parts of it you see differently. For whatever area that you have knowledge about, you probably see the world a little differently when that part of the world comes up. You will probably read reports coming out of a newspaper or on a TV show with a different perspective if they relate to the fields that you're in. You read things in the newspaper about there's a cure for this, there's a cure for that, and you just think, "Maybe that's overselling it a little bit." Particularly when it's done on a small scale or in a test tube or something like that.

There's a lot of things with headlines and hype, and you realize all the hard work that goes from a small discovery to really a major one. I don't know how many times I've seen cancer been cured in the newspaper, but in real life, it's a hard problem.

Tech: What things do you do outside of research, beyond the world of the laboratory?

Langer: In addition to being with my family, I exercise a lot. I run; I lift weights. We also have a softball team at the lab. Other than sports, the one that's of a bit of an unusual type is that I do magic. I haven't done big shows lately, but for a number of times I've done shows for the MIT community, for a few hundred people.

Tech: What personal qualities do you think are important to being an inventor or scientist?

Langer:To be a scientist I think requires lots of qualities. Some people are just incredibly curious. I've seen chemists in my lab just marvel at the way a crystal forms. In my case, one of the things that's been very important to me is to see the work we do go some place and help people. I've always been a big believer in science for the good it can do, and we've gotten a lot of satisfaction out of seeing that happen. I write scientific papers, and some of that work is pretty basic, but I like to do it in the context where a real life problem may be solved or has the potential to be solved.

Education and innovation

Tech: One of the goals of the Lemelson-MIT Prize is to inspire innovation in young Americans. Do you think inventiveness can be cultivated? How much of this quality is nature and how much of is nurture?

Langer:That's a good question. I think probably it's some of both. People need a to be born with a certain amount of curiosity and intelligence. But it's also very helpful for people to have good role models. I was lucky as a post doc to have a very good role model, my advisor Judah Folkman. He was very creative, and it was a great to see how he believed that anything was possible.

In my own laboratory, I let people see examples of what I do. I have people running in here all the time about "can you patent this, can you patent that." When people see other people do it, it increases their confidence and the awareness of the way they think, and they're more likely to succeed.

Tech: How do we encourage young Americans to be innovative?

Langer:I think programs like the Lemelson-MIT program is very good in the sense that they give these awards and they have web sites, where people can learn about them. I learned a lot about them myself. So I think by providing information to students, by helping them get positive role models. I read that a couple of people who won these awards speak at programs in high schools. I think all of these kinds of things provide positive publicity associated with invention and innovation.

Tech: How well does MIT's environment foster innovation, for example, with the UROPprogram?

Langer:As I mentioned before, good role models, which is one of the things that the UROP program provides, are very helpful. I think that MIT does a great job on every level and is probably the best place I've ever seen, from having been to different universities giving lectures. The UROP program is a terrific way for undergraduates to learn research, and it's what makes MIT unique.

I also think that MIT goes a couple steps beyond just the education. MIT has always had strong ties to industry. There's a terrific Technology Transfer Office and a Industrial Liaison program. So they have all these things that expose students and professors to a broader spectrum of things, which I think encourage innovation very well.

Tech: How have your parents influenced your achievements in science?

Langer: When I was a little boy, my father always played math games with me. He also got me interested in science by giving me these chemistry sets and microscope sets. I think he was a very stimulating person to be with both by example and by interaction, building the radio with him. It was wonderful to be exposed to that as a young child.

Tech: What's your role as a parent in bringing up your own children?

Langer: I have three little kids myself. The roles we play as parents, in every way as a role model and interactions with the kids are really important. Sometimes I bring my kids here to the lab on the weekends, when the post docs and even myself do experiments. They get exposed to that at an early age and see that these things are possible. On the other hand, I also want them to have a well-rounded life. My eight-year-old is interested in soccer, so I certainly want to encourage that. My seven-year-old daughter likes gymnastics, and I encourage that also.

Tech: What are your goals for your kids?

Langer: I want them to be happy, and that's what the goal that my mother and father had for me. They never pushed me that hard and they exposed me to different things, my number one goal for my kids is to just have happy happy lives.

Protecting innovation

Tech: As an inventor with 320 patents, do you believe that the current patent system provides adequate protection for inventions?

Langer: Interesting question. I think it's a reasonably good system, although ways of trying to get approvals more rapidly would be helpful, particularly in fields like medicine. As opposed to a household product patent, which you might be able to sell tomorrow, medical patents take a much longer time to develop into a product because it has to go through all the clinical trials.

In certain areas like in medicine, perhaps patents should be treated differently than say, technology patents. Maybe it would be good at least to consider ways to get extended life on the patent.

Tech: Products from life-critical research tend to be closely monitored by the FDA. How have your experiences been with the FDA?

Langer: My encounters with the FDA have been quite positive. I should say, not that it has anything to do with it, I'm also on the FDA Science Board, which is the highest advisory board. What happens is we've done some of the more basic stuff in our laboratory and different companies license it. Those companies have good regulatory people who deal directly with the FDA.

What's happened though in general is that the FDA deals with the kinds of stuff we've been involved with as being more innovative. With things that are either more innovative or more life threatening, the FDA fast-tracks them. I think the FDA actually has been, in our case, pretty responsive.

Tech: There has been recent controversy over the use of pharmaceutical products such as Redux. Have you ever experienced similar problems with your work?

Langer: In the brain tumor case, the company that licensed the technology originally wanted to get a broader approval than what they ultimately got. The way the approvals work is often complicated. With many products, indications start out narrow and broaden later.

A separate issue has nothing to do with the FDA but deals with the marketing of medical products. A product may be only approved for something. For instance, Redux might only be approved for people with extreme obesity, but now that it's out there, certain clinicians might decide to prescribe it for almost anything. That makes it complicated, and sometimes there may be encouragement from the companies too.

We haven't seen that much controversy on the things that I've been involved with directly. But certainly there are issues that have come up. For example, silicon breast implants is an area that was and still is, somewhat controversial.

Tech: You direct and teach a summer program at MIT called Advances in Controlled Release Technology. What do you try to achieve through the program?

Langer: All the kinds of stuff we've just talked about. I had this idea in 1980 and this will be the 19th year that we've done it in the U.S. and we've also done it in Europe. It aims to take somebody and really teach them the field, so they know how one might take a drug or pesticide or any entity and be able to create a delivery system that could solve particular problems. So we teach them all kinds of principles of polymer science: transport phenomenon, regulatory issues with the FDA, mathematical modeling so you can predict what you've done.

Tech: What are you thoughts about basic research versus applied research?

Langer: Basic research is very important, but ultimately you need both. Basic research enables discovery to be made that can have very broad impact. Applied research is important so you can take those discoveries and use them for different things. Like I said earlier, as you come up with something, you have no idea what it's going to be used for. In fact the initial research we had with polymers actually had to do with studying how blood vessels work. I was trying to develop an assay for that, which was very basic work.

The future of learning, science

Tech: Major advancements in science began during the Renaissance. As we approach the end of the millennium, some people have speculated that we are also arriving at the end of novel scientific discoveries. Do you agree?

Langer: I don't think so. There is still much more that we want to discover and will discover as we move to the next millennium. My own feeling is that there's just so much to learn. Certainly in the biological area, some advances in molecular biology opened up all kinds of opportunities to learn things that we've never learned before. There's also opportunity for learning in material science and chemical engineering, particularly in areas that cross over with biology. I think about that all the time: how molecules are transported across different barriers, how can we learn more about the immune system to make high quantities of antibodies for better vaccines.

I think there are just so many things that we don't understand and what's good about this particular time is that we live in an environment where science is certainly appreciated and where you have resources to do things in science that are continuously getting better and better.

Tech: We've been pursuing new knowledge since the beginning of time. Will we ever reach a full understanding of the Universe?Where do you think the limit lies?

Langer: That's a hard question. If I were to look at what happened in the last hundred years, it's just incredible what we've learned. So extrapolating on that, I expect with the tools that are in place, we're going to learn an incredible amount in the next hundred years. I don't know where you draw the line, but I just think that at least in the near future, we're going to learn an awful lot.