Gene Genie

Robert Langer smiles when people tell him he's playing God. He's not afraid of the job. "One could say that God decided that a child would be born with a defect, and would be ill, and therefore we have no right to cure him," he says.

Robert Langer smiles when people tell him he's playing God. He's not afraid of the job. "One could say that God decided that a child would be born with a defect, and would be ill, and therefore we have no right to cure him," he says. "I think we have the right. If your son were ill, you would also want me to play God, replace the defective gene with a normal one, and save him."

Langer, a 55-year-old American Jew, is one of the world's leading scientists, as demonstrated by the fact that he has received every possible prize (save the Nobel Prize). He came to Israel last week to receive the Harvey Prize, the most prestigious prize given by the Technion - Israel Institute of Technology in Haifa. Last year he won the Draper Prize for achievements in engineering, which is considered on a par with the Nobel Prize. The Boston Globe called him "the smartest man in Boston," Forbes Magazine and BioWorld named him of the 25 most important people in the world of biotechnology. Time Magazine wrote that he is one of the 18 most important people in the world of science in the United States, and one of the 100 most important people in the country.

He is the only person in the United States who is a member of the three American academies: the National Academy of Sciences, the National Academy of Medicine and the National Academy of Engineering. His inventions have led to the establishment of over 25 companies. He has written 700 articles, listed 500 patents and in general has changed the way in which doctors think about medications. Although he is one of the most well known professors in the world, and could allow himself to concentrate on research, he continues to teach bachelor's and master's degrees students at MIT (the Massachusetts Institute of Technology), while at the same time directing a huge team of about 90 researchers and scientists, many of whom have already become leaders in their field. Langer says the success of his students is the most precious thing to him, and unlike many professors who say similar things, he seems to really mean it.

The virus strategy

One of the Langer's current projects is the development of a method to replace defective genes with normal ones, a field that is called gene therapy. "Many people suffer from genetic diseases," he says. "They don't produce certain substances because the gene that should give the manufacturing instructions is defective. The idea behind gene therapy is that it is possible to locate the defective gene on the DNA sequence, and to replace it with a normal one." But changing a gene is not like changing a tire. First one has to find the right place on the huge DNA sequence, and primarily, one has to find a means of delivering the healthy gene and getting it to replace the defective gene, without creating a new problem.

"One approach favors delivering the gene by means of a virus," says Langer. "The problem is that the virus can cause damage. Our method is to use a synthetic polymer (a polymer is a long molecule composed of a string of small molecules that create a sponge-like structure with small holes of different sizes). The polymer arrives at the location and disintegrates after completing its job. The problem is that it doesn't do the job as effectively as a virus. We are facing a dilemma: The virus is more effective, but dangerous. The polymer is not dangerous, but is less effective."

The virus strategy recently suffered a mortal blow. A group of doctors tried to replace the gene causing SCID (severe combined immune deficiency), a hereditary disease created as a result of a mutation in one of the genes responsible for the development and functioning of the immune system. The disease causes a baby to be born without an immune system to protect it

even from the simplest infections, which means it has to be placed in a plastic bubble immediately after birth. The doctors used the virus in order to deliver a healthy gene to the location of the defective gene, and exchanged the genes. But something went wrong along the way: Of 11 children who received the treatment, two developed a serious and aggressive cancer. The doctors admitted it was their treatment that caused the development of the cancer, and the U.S. Food and Drug Administration (FDA) has postponed additional experiments.

Although Langer works in a different way, he is quick to defend his fellow scientists. "They call us doctors, but usually we don't cure, we help. Most of the existing medications don't cure the disease, but help the body overcome its symptoms. It's true that gene therapy has the potential of curing, since sometimes the genes are the source of defects causing diseases, but there is still a price to pay. People who go to receive treatment for cancer know that the treatment will lead to the killing of the tumor, but will kill healthy cells as well. If 11 children were about to die and now, after treatment, nine children will live and two will die, I'll take that risk and I want the treatment."

Following the path

Isn't it arrogant of you to assume that you can intervene in the process of evolution and repair a genetic defect?

Langer: "No, I don't think it's arrogance. In the past, doctors encountered problems that looked no less tremendous and threatening at the time. The life span today is double what it was 100 years ago. Children who in the past would have died, today are alive thanks to developments in medicine, in the field of vaccinations, et al. Maybe gene therapy is different from developing a vaccination. But actually we are following the path paved by our predecessors. We are trying to overcome medical problems and to prevent human tragedies from taking place."

But DNA is different, it's the last frontier.

"Today it looks like the last frontier. Before they knew about the cell, they thought the cell was the last frontier. In this field everything is relative, and assumes the proper proportions only years later. DNA is undoubtedly the next frontier, but only in the future will we know if it's really the last frontier. As a scientist, all I want is to understand this frontier and to try to save lives."

It must be said in Langer's favor that he doesn't stand in one place. Beyond the development of methods in the field of delivering medications (see box), Langer and his team are also involved in tissue engineering, which seems like science fiction.

"Sometimes a certain tissue stops working, or is damaged," he explains. "With tissue engineering we ask one question: Can we create new tissue for that person. If his liver is damaged, can we create a new liver for him, or perhaps a new spinal column for people injured in an accident."

When asked if he isn't worried about the possibility that the methods he is developing will be a stage on the way to ordering specific traits ("Could we please have a child with blue eyes?"), and perhaps to creating a new species of human beings, Langer replies: "I don't think that science is a slippery slope, it's progress. We often ask ourselves who will decide what is right and what is not, and what use should be made of science. Experience teaches that at the end of the process, there are laws, and bodies are established, and they organize the knowledge. That is probably what will happen in the field of genetics as well. In effect, it's already beginning to happen."

And in your worst nightmares, aren't you afraid that in the future you'll see how your methods and the knowledge you discovered are being exploited, and you'll say to yourself, "God almighty, what have I done?"

"No," replies Langer firmly. "In my nightmares I'm afraid that my treatments won't succeed and the patients won't be offered a solution. I'm not concerned that someone will misuse what I have invented, in fact I don't even think about it. My nightmare is that I won't succeed in helping people."

A chip to change the world

Prof. Langer became world famous after developing a new field in biomedical engineering in the 1990s, when he succeeded in building a mechanism that releases medications into the body in the proper dosages and at predetermined times. The trick he used was to trap the molecule of the drug in a polymer, and to adapt the sizes of the holes in the polymer to the size of the molecules he wanted to release. After 15 years of development he found a way to control the rate of release of the molecules from the polymer.

"For years, people envisioned a wall-like substance, and said it was impossible to transmit molecules through it. They tried to make holes in the substance, but then the molecules leaked out of it quickly," says Langer. "We created a twisting and complex maze within the substance, which causes the molecules to leak from the wall [the polymer] slowly and at the required rate."

People who know him claim this is "a classical Langer solution," which only proves that he one of the most brilliant people in the industry. "As opposed to others, I don't take for granted that what I'm told is the truth. As opposed to what is generally thought, there are very few things in life that are impossible," he says.

This invention made it possible to give patient-friendly treatment with medications composed of large molecules. Instead of injecting the medications frequently, they are trapped inside polymers and their release into the body is delayed. In this way, instead of administering one injection per day, they developed medications that can be injected once a month. Within a short time, Langer became the chief engineer of the medical world, inventing, among other things, an electronic chip that stores and releases various chemical substances as required, from tiny containers embedded in the silicon layer. At present the chip is being used in clinical experiments in animals. "If the chip passes all the tests, it has the potential to change the world," says Langer.

Despite his tremendous talent and his impressive achievements, it looks as though the most important prize - the Nobel Prize - is still far away. Langer studied engineering, and despite the fact that he is involved in medicine and chemistry (fields in which the Nobel Prizes are given), he may not win the prize because those who award the prize are afraid of creating a precedent of someone winning the prize for achievements that are not in his field (there is no Nobel Prize for engineering).

"Only God knows if I'll win the Nobel Prize," he says. "God and the people in Sweden who award it. Usually, the Nobel is given to people who have discovered something basic, like the structure of DNA. On the other hand, I'm not really familiar with the criteria according to which the distributors of the prize operate. Nor do I know what criteria guided those awarding the Technion's Harvey Prize, but I'm happy I was chosen to receive it."