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Langer discusses importance of risk-taking in the life of an inventor

Robert S. Langer attributes some of his best research ideas to restlessness.

After Robert Langer, the nation’s top biomedical engineer, concluded an hour-long talk and slide show last week in Packard Lab Auditorium, a student stood to ask a question.

“What drives you?” the student asked Langer. “What is your philosophy?”

Langer had just shed light on the new age of medicine, describing miracles soon to come and miracles already commonplace. He had shown how new bioengineering therapies are offering hope to cancer sufferers, burn victims, organ-transplant patients and people with macular degeneration.

His answer to the student was simple.

“I always ask myself, ‘How can I make the greatest impact?’” he said. “I believe that it’s good to dream. It’s good to take risks. And it’s good to expose yourself to areas you don’t know that can stretch you.”

Langer directs the nation’s largest biomedical engineering lab, the Langer Lab at MIT, which supports more than 100 researchers. He holds 600 patents and 150 major awards, including the U.S. National Medal of Science; the Albany Medical Center Prize in Medicine and Biomedical Research, largest U.S. prize for medical research; and the Lemelson-MIT Prize, largest in the world for invention.

In two talks at Lehigh on Nov. 30, Langer stressed the importance of risk-taking—and failure—in the life of an inventor.

Before he completed his Ph.D. from MIT in 1974, Langer said, he had received 20 job offers from oil and chemical companies. He turned down each one, hoping to do something that would improve the quality of people’s lives.

Langer then set out to find a job as a teacher. He had helped start an alternative high school for inner-city students as a graduate student, and he envisioned a career for himself in education.

“I wrote to a bunch of schools,” Langer recounted, “but no one wrote back. I thought to myself, ‘This isn’t going to work. Now what?’ I’d always been interested in medicine, so I wrote to medical schools and hospitals, but again, no one replied.”

A colleague told Langer that Judah Folkman, a cancer researcher at Harvard Medical School, “sometimes takes unusual people.” This time, Langer’s letter produced a phone call. Langer joined Folkman in his lab and began studying angiogenesis, the process by which new blood vessels are formed.

“Our theory was that if we could stop the growth of new blood vessels, we could stop the growth of tumors and cancers. We looked at the two parts of the body—cartilage and cornea—that do not have blood vessels.”

Langer located a slaughterhouse in South Boston that began shipping boxes of bones to the lab. On learning that tumors implanted in the eyeball develop the ability to grow blood vessels, he and Folkman fashioned a polymer with a “cartilage inhibitor” and implanted it alongside a tumor in the cornea. But it took 200 tests before a protein inhibitor could be coaxed to pass through the polymeric membrane and finally halt the tumor’s angiogenesis.

An exciting, but frustrating time

The early years with Folkman, and then at MIT as an assistant professor, were exciting but frustrating, Langer said.

“My first nine grant proposals were turned down,” Langer said in a talk to faculty and graduate students in Iacocca Hall. “My work was considered unconventional; it went against traditional disciplines. I was studying angiogenesis. The granting agencies said, ‘How can a chemical engineer do this?’ I wanted to treat diseases. The agencies wanted to do mathematical modeling.

“I was pretty depressed for about six months. I kept plugging away because I had no alternative.”

Langer’s fortunes began to turn when he received his first major grant—from Merck. By the late 1970s, other researchers were testing the results that Langer had recorded in his first published papers. Langer expanded his interests to the timed release of drugs through new polymeric coatings. The results came at their own pace, often maddeningly slow, as some experiments took three years or more to complete.

“We cut the polymer into extremely fine slices, but they were still almost impermeable—like traffic in Boston,” Langer said.

Even slower than the lab results was the process of obtaining government approval for some new drugs, Langer said.

“It was the late 1970s when we published our first papers on the effectiveness of polymer-wrapped cartilage inhibitors in countering angiogenesis. But it was not until 2004 when the FDA [U.S. Food and Drug Administration] approved the first angiogenesis inhibitors.

“But in the three years since then, 15 other angiogenesis inhibitors have been approved for treating cancer and macular degeneration, and there are currently more than 1,000 inhibitors in clinical trials.”

Langer’s patents have been licensed or sub-licensed to more than 200 companies, including pharmaceutical, chemical and medical-device companies. Some of those companies are headed by from graduate students and post-docs from his lab, known as the Langer Lab, which currently has more than 100 researchers.

Technology transfer, Langer told the professors and graduate students at Iacocca Hall, is critical to academic research.

“Technology transfer creates products and jobs, makes an impact and ultimately helps save lives. But 20 to 25 years ago, the idea of trying to commercialize your technology was frowned upon at most universities. Since then, most universities have come to consider technology transfer not only good but vital.

“Look at property values, for example. In the 1970s, Kendall Square, the area around MIT, was a slum. Now it has hundreds of companies, along with restaurants and hotels. The area has undergone an enormous transformation, thanks to technology transfer.”

Restlessness can be a plus

Langer attributes some of his best research ideas to restlessness.

“I’m always thinking to myself, ‘What’s going to be next?’ Twelve years ago, I was watching a show on PBS on computer chips and how they’re made. I thought, ‘What a great way to do drug delivery! Can we make a chip for controlled release of drugs?’”

The result was a collaboration with an MIT materials science and engineering professor that produced a dime-sized microchip dotted with tiny wells, or reservoirs, that contain medication and are covered with gold. When a voltage is applied selectively, the gold covering one of the reservoirs dissolves and releases the drug.

In 1996, Langer and his colleagues were the first group to win FDA approval for a method of delivering localized chemotherapy to cancer patients. The group developed a polymer coating for a drug administered to patients undergoing surgery for glioblastoma, an incurable form of brain cancer. The polymer, which exposes only targeted cells to the drug, was the product of 15 years of research and many rejections by funding agencies.

Langer has also invented a heat-sensitive string for suturing internal wounds. Tied into a loose knot, the string tightens when placed into the body through a tiny surgical incision.

Langer’s group is currently working on a 3-D biodegradable polymeric scaffold on which specified types of cells can grow and form tissue. Someday, Langer hopes, the scaffold will help damaged organs regenerate, thus reducing or eliminating the need for organ transplants. A scaffold coated with neonatal skin cells, he said, was used recently to heal a baby boy who had suffered extensive burns over his chest and neck.

Two ingredients of his work, Langer said, are the consistent application of engineering principles and the ability to work with researchers from other fields.

“We have people from 10 different disciplines—including physics, electrical engineering, cell biology, chemical engineering and materials science—in our labs. We try to recruit people of different backgrounds who have a great passion for working together and fixing things.”

Langer spoke for an hour without notes, and drew laughter and applause from the Packard Lab audience.

He confessed he is not a naturally gifted speaker. As an eighth-grade student, he said, he was required to give a speech lasting one and one-half minutes to his class.

“It was the first time I gave a speech in public,” he said, “and I was really nervous. I wrote out the speech, I memorized it, and I rehearsed it two nights in a row standing in front of the mirror in my parents’ bedroom.

“The next day I recited the speech in front of the class. Everything went well, until the one-minute-two-second mark. All of a sudden I froze. I forgot the next word, then I forgot the rest of the speech. I stood there silently until the teacher told me to sit down. I got a poor grade, an F.”

In his talks, Langer cited the achievements of many of his former students.

“I’m incredibly proud of our undergraduates, graduate students and post-docs. They’re CEOs of corporations, they’ve started their own companies, they’re chairs of university departments and hospital departments.

“Many of the reviewers at the funding agencies haven’t done so well.”

Langer was introduced to the audience in Packard Lab by Lehigh President Alice P. Gast, who served as vice president for research at MIT before her appointment as Lehigh’s president in 2006.

After reciting some of Langer’s achievements, Gast said, “I have never known such a busy person who so readily makes time for family, friends, students and colleagues.”

Langer’s visit to Lehigh was sponsored by the W.M. Keck Foundation Grant for Applied Life Science Program and the Howard Hughes Medical Institute Grant for Undergraduate Bioscience Education. Both are administered by Lehigh’s department of biological sciences. Neal Simon and Vassie Ware, professors of biological sciences, are the principal investigators on the grants.

--Kurt Pfitzer

Posted on Tuesday, December 04, 2007

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