Drug Deliveryman

By David Bjerklie

Imagine writing a letter of life-and-death importance and trying to mail it only to discover that you have the wrong address, the wrong envelope and no way to buy a stamp. Robert Langer of the Massachusetts Institute of Technology has been wrestling with a problem very much like that for 25 years. In his case the letters are life-saving drugs, and the goal is to deliver them to the right place at the right dose and at the right time.

Langer's career as pharmaceutical postman began in 1974 when he graduated from M.I.T. with a doctorate in chemical engineering. He had 20 job offers from oil companies but opted instead for a postdoctorate position at Children's Hospital in Boston with Judah Folkman, one of the world's leading cancer researchers. It may have seemed an odd choice for an engineer with a bankable resume, but it gave Langer a unique perspective on a fast-growing field. He has since become the leading pioneer of modern biomedical engineering, earning scores of awards and distinctions and nearly 400 patents.

His assignment in Folkman's lab was to find a way to release gradually a stream of large organic molecules into the tissue of a laboratory animal. Researchers had already tried encasing large molecules like the one Langer was testing in polymers (long-chain molecules, such as silicone, that are semipermeable to certain types of molecules). Unfortunately, this particular molecule--like most of the new drugs being created in biotech labs--was much too large to fit through the tiny holes in any of the available polymers. The problem, polymer experts told Langer, was unsolvable.

But he solved the problem simply by turning it upside down. Rather than try to sift marbles through a screen too fine to let them through, Langer in effect wrapped the screen around the marbles, creating a three-dimensional matrix honeycombed with marble-size chutes and ladders that would allow his molecules to slowly work their way out. It was a breakthrough that ushered in a new generation of drug-delivery systems.

Langer also changed forever the way the materials used in these systems are designed. Researchers in the past had relied on off-the-shelf materials for medical applications. (The fabric in the first artificial heart, for example, was the same polyether urethane used in women's girdles.) Langer reversed the search process; in his lab, researchers first determine the exact physiological requirements of a system and then design a polymer to meet those specs.

In 1986, for example, Langer and neurosurgeon Henry Brem devised the first dime-size chemotherapy wafers to treat brain cancer. These wafers release powerful cancer-fighting drugs slowly in the site where a tumor has been removed in order to kill any cancer cells the surgeon has missed. By confining the drugs to the site of the tumor, the effects on other organs are minimized--always a major consideration in chemotherapy. The same concept has since been applied to prostate, spinal and ovarian cancers.

Langer has also pioneered remote-control systems in which the rate at which the drug is released can be varied using ultrasound, electric pulses and even magnetic fields. This team has recently developed the prototype of an implantable "pharmacy-on-a-chip" that they hope someday will not only monitor a patient's blood chemistry but also prescribe a carefully measured dose of the proper medicine precisely when it's needed.

Langer's approach to the design of biomaterials has paved the way for the emergence of the new field of tissue engineering. Working closely with Harvard's Joseph Vacanti, Langer is using tailor-made polymers to build tiny scaffolds that can then be seeded with skin, cartilage, liver or other cells. The idea is to provide a temporary structure that cells can colonize and upon which they can eventually grow into a functioning organ--at which point the scaffold dissolves away. Langer foresees the day when scientists will be able to grow a new liver or pancreas for patients waiting for scarce donor organs. Skin grown using Langer's principles has been approved by the FDA, and cartilage for rib cages is in clinical trials.

Langer, who in lives in the Boston suburbs with his wife and three children and throws an annual barbecue for his lab group at his beach house on Cape Cod, is something of an amateur magician. Folkman, Langer's original mentor, remains one of his biggest fans. "He's a true genius," says Folkman. "He sees answers to problems in such unique ways you can't trace the steps he took." In other words, he's very good at pulling rabbits out of hats.