There was a time when medicine and chemical engineering hadn’t been properly introduced. Then Robert Langer crashed the party.
That was in 1974, when Langer, now Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering at MIT, signed on as a postdoc in Judah Folkman’s cancer lab at Boston’s Children’s Hospital. Mingling with the surgeons and scientists, the young chemical engineer was far afield. Far enough, in fact, to discover his uncommon calling: molding materials that turn biological discoveries into medical cures.
Synthetic polymers are Langer’s specialty. He crafts, from plastic, implantable dispensing machines for some of biotechnology’s most esoteric therapies, as well as safer delivery devices for more conventional medicines. Langer’s work is one of the pillars of the multibillion-dollar drug-delivery industry. But the pace of his progress is such (his name appears on more than 330 patents) that he has populated not one, but two new industries with ideas and students. Langer’s second sphere of innovation is tissue engineering, an emerging discipline in which his synthetic polymers are helping researchers grow replacement body parts in the laboratory.
In his award-cluttered MIT office, Langer spoke with Technology Review Associate Editor Antonio Regalado.
TR: Biomaterials are the common thread in your work. What are they, and why are they important?
LANGER: A biomaterial is any substance other than food or drugs contained in a therapeutic system that’s in contact with biological tissues or fluids. Biomaterials have been around for a while-more than 2,000 years in the case of dental fillings. Pound for pound, fillings are the most common biomaterial in use. Newer applications of biomaterials in drug delivery and tissue engineering are important because they have the potential to revolutionize certain medical treatments.
TR: How have doctors chosen which materials to use?
LANGER: There’s some interesting history there. Until the 1970s physicians tended to adapt off-the-shelf materials designed for consumer applications. For example, a polymer called polyether urethane used in artificial hearts was originally used to make women’s girdles. Dialysis tubing was originally sausage casing. And breast implants, one of them was actually a lubricant and the other was a mattress stuffing. They just used any material they could find that resembled the tissues they were trying to replace.
But the off-the-shelf approach has led to a number of problems. For instance, when blood hits the surface of an artificial heart, clots may form and the patient may suffer a stroke.
TR: Weren’t chemical engineers or materials scientists involved in choosing which materials to use?
LANGER: Well, not very much. So at the very beginning of my career, I proposed a different approach to designing biomaterials, which was to ask “What do you really want in a biomaterial from an engineering, chemistry and biological standpoint?” and then synthesize it from first principles.
TR: At the time, was there any precedent for taking that kind of approach?
LANGER: Not really. And I can tell you that when I started out, this was very odd work for a chemical engineer to be doing, since it wasn’t mathematical modeling or something to do with the oil or chemical industries.
TR: What types of problems can better biomaterials solve?
LANGER: There are many applications, from pacemakers to contact lenses, but I have worked mainly on solving problems related to drug delivery. The things you’d like to do are keep drug levels within a certain range, target drugs to a particular cell type or tissue, or help out with drugs that don’t last long in the body, like peptides or proteins. It’s an important area, since up to 100,000 deaths a year in the United States each year can be attributed to adverse drug events, such as an overdose. For instance, I have synthesized polymers shaped to trap or encapsulate drugs, then release them at a precise rate.
TR: What are the engineering challenges in using polymers for drug delivery?
LANGER: It starts with an engineering design approach. For example, in the area of degradable synthetic polymers we are remarkably limited in terms of what we can put in the human body. For many years, the only degradable materials available were some synthetic polyesters used in sutures. But these get spongy and ultimately fall apart. If you put a drug into that kind of polymer, that could lead to a burst of drug release. That could be fatal with a potent drug like insulin.
What you’d really like to do is design a system that would erode, in much the same way a bar of soap dissolves. Along with my students, I went through an entire engineering analysis to determine how one would do this, and came up with a family of polymers that we call polyanhydrides.
TR: So you solved the engineering question, but are there applications for these polymers?
LANGER: A surgeon at Johns Hopkins named Henry Brem came to me about using these polymers in a new brain cancer treatment. There were many scientists who doubted us. They said we wouldn’t be able to synthesize these polymers. When we did, they said that the polymer would be toxic and that it couldn’t be manufactured.
Today as a consequence of studies done by us and others, polyanhydride matrices are used to deliver a powerful chemotherapy called BCNU to treat brain cancer. Normally, BCNU is delivered through the blood, and it is very toxic to the liver, kidneys, and spleen. In this case, the surgeon removes as much of the tumor as possible, but also places up to eight small polymer-drug wafers at the tumor site. The drug is slowly released from the polymer for one month to kill remaining tumor cells and harmful side effects are minimized. One recent clinical trial showed that after two years, 31 percent of the treated patients were alive whereas only 6 percent in the control group survived. This was the first new brain cancer therapy approved by the Food and Drug Administration in more than 20 years.