Many knowledgeable people think Robert Langer is a revolutionary.
Langer, the Germeshausen professor of chemical and biomedical engineering, is at the forefront of a technological movement that drastically could change medical care. At its core is a whole new way of marrying engineering and biology.
One of his key tools is a class of materials called polymers. The class encompasses ordinary plastics, but the polymers Langer seeks must have special properties.
An early effort, for example, involved finding a material that could be implanted in the brain, where it would release drugs directly into a tumor over a period of months. “What we wanted was a polymer that would dissolve the way a bar of soap does,” he notes.
But that wasn’t all. The substance couldn’t interact chemically with the drug it harbored, and its breakdown products had to be completely safe.
Langer ultimately found the right material. Laced with a supply of a potent chemotherapeutic agent, and formed into a dime-sized wafer, it created a delivery system that has become a medical success story. Many patients with a brain cancer that’s often fatal within months are now living years instead — and all who get the treatment are spared the sometimes harsh side effects associated with conventional delivery of the drug.
Langer has since moved on to other challenges. One is helping lead the drive to grow new tissues and organs from seed cells.
“Success has been achieved with skin, and we’re essentially there with cartilage,” he says. A group in his lab has also produced new blood vessels, and work is proceeding on new livers. Even new hearts and lungs may someday be possible. “I think it will happen,” says Langer, “though it could be many, many years.”
The faculty member, with an astounding 324 patents issued or pending, has been widely honored. Among a host of prizes he has received is the prestigious Lemelson-MIT Prize, given annually to outstanding inventors.
Still, it’s clear one of his favorite badges of honor is his role in educating leaders in bioengineering. “Of my former graduate students and postdoctoral fellows, more than 70 are now university professors,” he notes.
Much of the lab’s work is in fact carried out by grad students. Langer, whose reputation draws outstanding applicants, is at pains to pick those who can handle the tough task of taking an idea from concept to working technology.
“I look for people who are highly motivated,” he says, “who like to be semi-independent, and who can think big.” He typically develops a close and mutually respectful working relationship with students. “I generally conceive of the overall idea,” he says, “and they come up with a lot of the specifics.”
What follows is a look at “the specifics” as they are unfolding in three projects under way in Langer’s lab. Helping new tissue grow
While modern surgery can offer near-miraculous help for individuals with deformed facial features, the improvements often come at a high cost in pain and can require a lot of hospital time. But a technology in development in Langer’s lab could markedly reduce the amount of surgery needed to help these and other patients.
How would it work? Picture a treatment where the doctor makes a few strategically placed injections, then triggers the reconstruction by simply shining a light on the skin over the features being rebuilt.
Jennifer Elisseeff wants to make such scenarios a reality. Elisseeff works with polymers mixed with a photoinitiator — a substance that, when exposed to the right type of light, can turn a liquid containing polymers into a semi-solid called a hydrogel. “Think of it as almost like jello,” she says.
The method may seem like magic but in fact it’s basic chemistry. The light activates the photoinitiator, the photoinitiator causes the polymer chains to join together in networks, and presto — there’s a gel.
This type of technology is already in use: It’s being tested, for example, as a way to repair tears in lungs. But Elisseeff wants to apply it in a way that minimizes the need for surgery. “The surgeons I work with,” she notes, “are interested in techniques that don’t require the use of a scalpel.”
She’s been focusing on the use of cartilage. This tough, slippery substance plays a variety of roles in our bodies, giving shape to features like ears and noses, and serving as the main buffering tissue in our joints. A loss of it, meanwhile, can be devastating. In osteoarthritis, the cartilage in joints may disappear. “Then you have bone grinding against bone,” notes Elisseeff, “which can be incredibly painful.”
Using a hydrogel to build cartilage involves seeding the polymer solution with cartilage cells, then injecting it where you want to grow new tissue. When the light coming through the skin turns the solution into a gel, says the student, “it holds the cells in place, and they can produce their own matrix.”
As the cartilage grows, the polymer slowly dissolves. Eventually, the gel is gone, leaving new cartilage behind.
Though Elisseeff has shown in lab experiments that it’s possible to form hydrogels under skin, more work is needed before the technique is ready for clinical use. Elisseeff may not be directly involved. Having nearly completed her PhD work, she’s planning to finish medical school — she’s well along toward a medical degree through the Harvard-MIT Division of Health Sciences and Technology — and to conduct research elsewhere.
Still, she’ll continue to focus on improving patients’ lives. “One reason I like working with cartilage,” she notes, “is that so many people could benefit from cartilage replacement.”
Tiny craft to deliver drugs
Proteins are key components of our bodies. They make up everything from hair (mostly composed of keratin) to muscle to the many hormones that keep our systems operating.
Proteins, though, are today being used to create more and more drugs as well. Insulin was one of the first protein-based agents, but there are now many others, from interferon to interleukin 2 — the latter employed to treat various cancers.
Yet while new protein-based agents show promise, most are still given in “one-shot” doses. That means patients get sudden boosts in exposure, followed by a drop-off to what may be trace levels in the blood.
Karen Fu says there’s a better way. “We want to deliver drugs so as to avoid peak-valley concentrations in the body,” says the student.
The approach is a variation on Langer’s wafer system for brain cancer. But instead of wafers Fu works with masses of drug-delivery craft, called microspheres, that are tiny enough to be given with a standard syringe — “no big needles,” she emphasizes.
The idea, originated by Langer, is that the spheres will slowly degrade, releasing their cargo of drugs as they do. Diabetics are potential beneficiaries, but there are many others. Fu notes that interferon aids against a form of hepatitis, “but you need an injection every other day.”
Still, challenges remain. Most involve safeguarding the protein-based drugs, which have complicated structures, on the risky journey from the test-tube into and through the bloodstream.
In a sense, Fu’s been preparing for such challenges for years. In high school, she says, “I liked biology and I liked math, so I decided to become a biomedical engineer, even though I didn’t fully understand what that was at the time.”
The Ohio native first explored bioengineering as an MIT undergraduate. She joined Langer’s lab in the mid-90s. “I’m someone who’s interested in getting things done,” she says, “and that’s partly why I chose Bob’s group; it’s so applications-oriented.”
Fu has already made strides toward creating microspheres that can ferry a protein-based drug payload safely into the bloodstream. Using a form of the testing technique called spectroscopy, she can tell if a drug harbored by a microsphere has retained its normal shape — a crucial concern.
That’s just one of the advances required. Still, Fu believes the system will eventually prove widely applicable in delivering protein-based drugs. “Wouldn’t it be great,” she says, “if instead of having to have an injection several times a week, you could just do it once every six months?”
A health-giving chip
For John Santini, graduate work has meant not only classes, research and occasional parties but also an appearance on World News Tonight with Peter Jennings.
It all happened in a hurry. “There I was, talking to these cameramen who had been everywhere, including traveling around with Bill Clinton,” he notes. “Then, they filmed me while I answered questions by teleconferencing with the reporter in New York.”
The segment aired that same night. The hour began with a report on the Senate impeachment hearings, followed by coverage of the Pope’s U.S. visit. “Then there was us,” Santini recalls. “It was really amazing.”
What sparked the interest not just of ABC News but of dozens of other media outlets was a technology described as a “pharmacy on a chip.” Its core is a silicon chip into which are etched many tiny “wells” — indentations a quarter the size of a salt grain that can hold drugs or other agents. Covering the wells are ultra-thin gold membranes. “By applying a voltage,” Santini notes, “you can make the membrane dissolve, and the stuff that’s inside comes out.”
Suitably designed chips could have many uses. If you attached a tiny computer processor and battery to an implantable version, you could program the chip to secrete drugs on a predetermined schedule — and spare patients the inconvenience and hazards of frequent shots.
Or, you might create an implantable chip that’s under radio control. “You could have several drugs on the chip,” says Santini, “and depending on how the disease was progressing you’d be able to hit it with any combination of drugs you wanted.”
The effort to develop the technology dates back over five years. Santini was a University of Michigan chemical engineering major when he enrolled in an MIT summer research program. There, he learned that Langer and a faculty colleague, materials scientist Michael Cima, had come up with the notion of a chip that delivers medicines.
“I started working on it,” Santini recalls. “We didn’t get far, but Bob and Michael told me, ‘It’s got enough potential that if you want to come here as a graduate student and take this on, you’re welcome to.'”
Today, while Santini is still improving the chip, he’s also pursuing other goals. One is launching a new company based on his MIT work.
Yet to be decided is exactly what products the firm will focus on first. Some may be medically oriented, says Santini, but others may not. One idea is a chip that gives off different fragrances. “You might see a pizza on the TV,” he says, “and at the same time smell a pizza.”
Whatever the decisions, Santini is excited about this next venture. “It should be interesting,” he says, “and it should be a lot of fun.”