Robert Weinberg Rewarded for Oncogene Discovery

Recipient of the 2011 ASCO Science of Oncology Award

Fran Lowry

May 05, 2011

May 5, 2011 — The scientist credited with discovering the first human oncogene, Robert A. Weinberg, PhD, has won the 2011 American Society of Clinical Oncology (ASCO) Science of Oncology Award.

Dr. Weinberg wins the award for "for furthering the understanding of cancer through his innovative and groundbreaking research," according to ASCO.

Dr. Robert Weinberg

Dr. Weinberg, a founding member of the Institute for Biomedical Research and a professor at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, is credited with discovering the first human oncogene — the Ras oncogene — which causes normal cells to form tumors.

He is also credited with isolating the Rb gene — the first known tumor suppressor gene — and he has shown how certain gene regulators contribute to cancer metastases.

Currently, Dr. Weinberg's lab is focused on the interactions between epithelial and stromal cells that result in tumors and the processes by which cancer cells become invasive and metastasize.

Commenting on these discoveries, immediate past president of ASCO, Douglas W. Blayney, MD, who is chair of the Special Awards Selection Committee, said the understanding of oncogenes, and how to manipulate them, is fundamental to personalized medicine, which is where the field of cancer is moving.

"The Ras oncogene — which is integral to the EGFR receptor-activated pathways used by tumor cells to keep themselves alive, growing, and multiplying — has been the target of common and effective nonchemotherapy treatments of colon and lung cancer, as well as other malignancies," Dr. Blayney told Medscape Medical News.

Not Bad for Someone Who Almost Flunked First Year Biology

Dr. Weinberg, who is the son of refugees who fled Germany, grew up in Pittsburgh, Pennsylvania.

"We spoke mostly German at home. My father was a dentist in Germany and in Pittsburgh, and I thought of becoming a doctor until I found out that doctors have to stay up all night," Dr. Weinberg said in an interview." I decided I didn't want to do that because I need my sleep, so I became a biologist instead."

Another reason was the fact that modern molecular biology had exploded onto the scene as a hot, new field, he added. "I just stumbled from one step in my career into the next without any forethought. One thing just led to another," he said.

Dr. Weinberg went to MIT because sons of friends of his parents had gone there. "That was the most I knew about college. My parents weren't much help there; they didn't know much about college either," he recalled.

He confesses that he did not exactly shine at MIT. "I had a rather lackluster career in MIT as an undergraduate. . . . Indeed, when I teach introductory biology now, I tell the students that when I took the same course that I now teach them, back in 1961, I got a D."

When it came time to go to graduate school, MIT was the only school to accept him. "They knew me on the basis of personal interactions rather than just my formal academic record, so I ended up staying at MIT."

Dr. Weinberg took a year off in the middle of grad school to teach at a black college in west Alabama. It was the height of the civil rights movement in the United States.

"I thought I needed to get away from MIT for a little while," he said. "Those were very interesting times. I used to go out on weekends bringing sacks of rice and flour to sharecroppers who had been evicted from their land for registering to vote. That's what was going on in those days."

After finishing his PhD in 1969, Dr. Weinberg earned 2 postdoctoral degrees, one at the Weizmann Institute of Science in Rehovot, Israel, and the other at the Salk Institute in La Jolla, California. But MIT wanted him back.

"While I was in La Jolla, the head of the then nascent MIT cancer center, Salvador Luria [renowned microbiologist and Nobel laureate] came to the Salk and told me I was going to be part of the new MIT cancer center, about which I knew virtually nothing," he said. "He didn't ask me whether I wanted to join, he told me I was going to join it. So I pretended indifference for a couple days before I accepted his kind offer. And I ended up back at MIT — not because I had thought of doing that but because he made what was ultimately a very attractive offer in terms of returning to a place I knew was a first-class operation."

For a while, Dr. Weinberg was a "super postdoc," working with David Baltimore, who had just discovered the reverse transcriptase enzyme and who was to soon win the Nobel Prize for that work.

In 1974, he set up his own lab in the MIT Center for Cancer Research.

The Most Important Discovery of His Career

With his own independent group working on retroviruses and then on transforming the genes of retroviruses, he went on to discover oncogenes in chemically transformed cells.

"I found that chemical carcinogens could go into a cell, damage or mutate the DNA in that cell, and convert a normal cellular growth-regulating gene into a potent cancer-causing gene, or oncogene, by changing the configuration of that gene."

In 1982, his group discovered the difference between the normal gene and the oncogene. Working with the DNA of a human bladder tumor, they found that the critical difference was a point mutation representing a single base of DNA that was changed.

"In my mind, that is the most important thing that has been done in my lab over the past 30 years," he said.

That same year, Dr. Weinberg moved to the Whitehead Institute, which is independent of but closely affiliated with MIT.

It sort of fell into our lap, unlike our earlier work, which was really hard.

Fortune continued to smile on Dr. Weinberg's research efforts. In 1986, a researcher in his lab isolated the retinoblastoma gene. "That was more a stroke of very good luck on the part of a postdoc of mine, but it did happen. It was a bit of an unearned run. It sort of fell into our lap, unlike our earlier work, which was really hard."

In 1999, his team discovered that 5 oncogenes are needed to transform a normal human cell into a cancer cell. Earlier, working with rats, they had found that at least 2 oncogenes are needed to do this. "In other words, human cells and rodent cells are quite different," he noted.

In 2004, they reported an important mechanism by which cancer cells become invasive and metastatic. They found that genes that are normally operative in the embryo can convert epithelial cancer cells into mesenchymal cells. That conversion, called an epithelial-mesenchymal transition (EMT), converts a more benign carcinoma cell into one that is much more aggressive.

Since then, much of his work has focused on the EMT. In 2008, his lab demonstrated that not only do carcinoma cells become mesenchymal when they undergo EMT, they also acquire the attributes of stem cells. Stem cells, which are self-renewing, could also potentially seed new tumors.

Don't Become a Researcher Unless You Like to Do Research

Dr. Weinberg and his wife, Amy, have 2 children — Aron and Leah Rosa.

Neither of his children are research scientists. "I never encouraged that in my kids. My son is studying cognitive psychology and my daughter is an architect," he said.

One very important thing is to enjoy what you're doing.

Asked what advice he would give to young people who want to become researchers and follow in his footsteps, Dr. Weinberg replied: "I wouldn't pretend to say that my life is a model for others, but I would say that one very important thing is to enjoy what you're doing. If you don't enjoy doing research, then no matter how committed you are to curing cancer, it won't work. You really need to enjoy the process of doing research — the daily struggle with the intricacies of nature."

He offered one more piece of advice: "Be prepared to move quickly in adapting what you are doing to new circumstances, rather than remaining on one fixed research trajectory for years and decades."

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