General Motors Awards $750,000 to World's Foremost Scientists for Cancer Research Breakthroughs

Researchers from the University of Maryland, the Massachusetts Institute of Technology and Stanford University Receive Honors

DETROIT, June 15, 2005; Three world-renowned scientists have been recognized by the General Motors Cancer Research Awards (GMCRA) program for their seminal contributions to cancer research.

The award recipients are:

* Angela M. Brodie, Ph.D., University of Maryland School of Medicine, Baltimore, Md., recipient of the Charles F. Kettering Prize.

* Gerald N. Wogan, Ph.D., Massachusetts Institute of Technology, Cambridge, Mass., recipient of the Charles S. Mott Prize, and

* Roger D. Kornberg, Ph.D., Stanford University, Palo Alto, Calif., recipient of the Alfred P. Sloan, Jr. Prize.

GM has made cancer research a key philanthropic priority, and this year marks the 27th anniversary of the GMCRA program. GM has given more than $51 million to the cause, and is committed to helping eradicate cancer and support cancer research.

Charles F. Kettering Prize

Dr. Brodie has been honored with the Charles F. Kettering Prize for pioneering the development of aromatase inhibitors, a new class of FDA- approved drugs, used widely today to treat breast cancer. The Kettering Prize recognizes the most outstanding recent contribution to the diagnosis or treatment of cancer. Brodie is the first female scientist to be awarded the Kettering Prize.

Aromatase inhibitors effectively treat recurrent breast cancer in postmenopausal women by reducing estrogen levels produced by the body, cutting off the fuel that promotes cancer cell growth. The drugs inhibit aromatase production, an enzyme that plays a primary role in the biosynthesis of estrogen.

Breast cancer in postmenopausal women often is hormone-dependent. Estrogen stimulates cancer growth by binding to estrogen receptors in the cancer cells. Without estrogen, the cancer cells cannot grow and divide.

Brodie began developing this novel approach of targeting aromatase in the early 1970s, initially working with her husband, who synthesized the early inhibitors. Brodie and her team then created the first selective aromatase inhibitor used in the treatment of breast cancer patients. Released for worldwide use in 1994, the drug, Formestane (4-hydroxyandrostenedione), was the first new compound in a decade specifically designed to treat breast cancer.

Her work paved the way for the development of three FDA-approved aromatase inhibitors for the treatment of breast cancer. Recent studies are proving these inhibitors to be significantly more effective therapeutically than the standard breast cancer drug, tamoxifen.

"Receiving the Kettering Prize is a tremendous honor and it's very gratifying to be recognized for the work we've done," said Brodie. "I am thrilled our findings are benefiting so many breast cancer patients."

She has since expanded her research into prostate cancer, one of the most common cancers in men, and is currently developing steroidal compounds that target key enzymes in the production of androgens, or male hormones, which play a role in recurrence of the cancer.

Brodie, a native of England, received B.Sc. and M.Sc. degrees from Sheffield University and a Ph.D. from Manchester University. Currently, she is professor of Pharmacology and Experimental Therapeutics at the University of Maryland School of Medicine. Brodie has received a number of awards during her distinguished career, including the Brinker Award for Scientific Distinction from the Susan G. Komen Foundation in 2000. She also has published more than 200 papers in professional journals. In addition, she is associate editor for Cancer Research and edits three other journals.

Charles S. Mott Prize

Dr. Wogan has been honored with the Charles S. Mott Prize for his studies related to Aflatoxin, a mold, food contaminant and human carcinogen that acts with the hepatitis virus to cause liver cancer, one of the five leading causes of cancer worldwide. The Mott Prize honors the most recent outstanding contribution related to the cause or prevention of cancer.

Wogan purified Aflatoxin, defined its structure and performed important studies establishing the link between Aflatoxin and liver cancer.

His achievements have had a significant impact in reducing the incidence of liver cancer in developing countries. His discoveries also have led to significant improvements in food monitoring, storage and processing. In areas where this is impossible due to social and economic issues, Wogan's research has led to the study of agents that can detoxify or inhibit Aflatoxin absorption.

Aflatoxin is found in food products such as peanuts, tree nuts, corn, cottonseed and milk. In China, where liver cancer is the leading cause of death in men, rates of the disease are about half in Beijing, which has low Aflatoxin levels, versus Qidong, a region with higher levels.

"It is a great honor to receive the Mott Prize, and it validates the importance of environmental agents and chemicals in the cause of disease," said Wogan. "The positive impact our research has had is extremely rewarding."

Wogan developed a strong interest in Aflatoxin and cancer research in 1963 as an assistant professor at MIT, after hearing a presentation by a UNICEF representative who discussed Turkey X Disease, a severe outbreak in the early 1960s that killed more than 100,000 turkeys. Later, experts determined the cause was toxic peanut meal and named the toxic agent Aflatoxin.

His initial interest led to a grant and a trip to London, where Wogan met with experts, then returned to the U.S. with spores of the Aflatoxin organism. Next, he teamed up with a fellow MIT chemist, which led to a lifelong friendship and collaboration.

At MIT, in addition to teaching and research, Wogan held senior administrative responsibilities, serving over a period of two decades as Head of the Department of Applied Biological Sciences, Director of the Division of Toxicology and founding Director of the Center for Environmental Health Sciences. Wogan also is a Senior Research Fellow in the Laboratory of Human Carcinogenesis at the National Cancer Institute, NIH, and Visiting Professor in the Department of Environmental Health Sciences of Johns Hopkins University.

His contributions have been recognized by election to membership in the National Academy of Sciences of the USA, the Institute of Medicine, the American Academy of Microbiology and appointment as Fogarty Scholar-in- Residence of the National Institutes of Health.

His research has been reported in more than 300 technical publications, monographs and books, and he is co-author of five patents. Wogan received his Ph.D. in physiology (major), biochemistry and microbiology (minors) from the University of Illinois. He joined the MIT faculty in 1961. Currently, he is professor emeritus of the Departments of Chemistry and Biological Engineering at MIT.

Alfred P. Sloan, Jr. Prize

Dr. Kornberg has been awarded the Alfred P. Sloan, Jr. Prize for his major contributions to groundbreaking work in discovering the inner workings of RNA -- in essence, he has solved one of the largest and most central structures of molecular biology. In addition, his discoveries help shed light on how a gene can mutate and cause cancer, giving cancer researchers a stronger foundation to do their work.

"You can't understand a machine if you don't know the place of all the pieces, and our discoveries have helped locate the parts of the machine that make RNA," said Kornberg.

His studies have centered on the RNA polymerase protein, a pivotal molecule that copies genes from DNA to RNA in a process called transcription, giving the human genome a voice. Kornberg and his team have focused their efforts on the isolation, structure and function of RNA polymerase and its many helper proteins.

Kornberg discovered the arrangement of 30,000 atoms in RNA polymerase and isolated nearly 50 proteins responsible for transcription and gene regulation. A virtually identical set of proteins perform the same functions in all plant and animal cells. Twelve of the proteins form RNA polymerase and are responsible for transcription, 15 direct the polymerase to the genes to be transcribed, and 20 form a mediator that regulates the process.

The mediator, which Kornberg discovered, is the long sought missing link in the transfer of information, which assures that the right gene turns on at the right place at the right time.

Also, in a scientific first, he and his team witnessed gene transcription in action. The gene has a "docking site" where the RNA polymerase sits. Then, a "finger" of a helper protein pokes into the enzyme's active center, and guides the beginning of the transcription process.

All of these findings create a foundation to determine how the process of gene transcription is controlled and regulated, which helps explain how a cell becomes a blood, nerve or liver cell, for example.

Earlier in his career, Kornberg discovered the nucleosome. Nucleosomes play a role in the process of gene transcription, in which the DNA sequence is copied or messengered into RNA. Nucleosomes also play a role in gene expression, the process in which the information in a gene is switched "on" to make proteins, the building block of life.

"Receiving the Sloan Prize is an honor and a form of encouragement. We love what we do and we're excited by it every day, but this serves as a sign that the work is viewed as important, correct and ultimately significant," said Kornberg. "Many wonderful collaborators over the years now know that their vital contributions are viewed in a favorable way."

A key collaborator throughout the years has been Kornberg's wife, Yahli Lorch, associate professor in the Department of Structural Biology at Stanford. Her contribution has been pivotal in the initial discovery of the nucleosome, and her work continues today in the areas of gene transcription and expression.

Kornberg received an undergraduate degree in chemistry from Harvard in 1967 and a doctorate from Stanford in 1972. He conducted postdoctoral studies at the Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. He joined the Harvard medical faculty as an assistant professor in 1976 and came to Stanford in 1978 as a professor in the Department of Structural Biology. He chaired the department from 1984 to 1992. Currently, he is a Winzer Professor in Medicine at Stanford University.

Dr. Samuel A. Wells, Jr., president of the GMCRA program, praised the award winners and cited their major contributions to combating this deadly disease. He noted that the laureates were chosen through a rigorous review process conducted by distinguished international scientists who served on the GMCRA program Selection Committees and Awards Assembly.

"Each of this year's GM Cancer Research Award recipients have made significant discoveries that will ultimately affect the lives of many people around the world," said Dr. Wells. "It is important that we continue to encourage cancer research by supporting the scientists who are dedicated to finding a cure for the disease."

The Annual Scientific Conference, sponsored by the GMCRA program, will be held at the National Institutes of Health on June 14 and 15. This year's conference will focus on breast cancer and will include a lecture by all of the award recipients describing their research. GM will present the prizes to the laureates during an awards ceremony at the Ritz Carlton in Washington, D.C. on the evening of June 15.

About the GMCRA program

The GMCRA program was founded in 1978 by former GM Chairman Roger Smith and Dr. Joseph G. Fortner, Attending Surgeon at the Memorial Sloan-Kettering Cancer Center. It was Smith's passion for eradicating cancer that led him to call on his friend, Dr. Fortner, to ask him to partner with GM to create "a Nobel prize for cancer research -- something to encourage the importance of continued research and idea sharing to wipe out this disease." The GMCRA annually recognize the outstanding accomplishments of basic scientists and clinical scientists in cancer research around the world. The first GMCRA were given on May 2, 1979.

The GMCRA program has previously awarded nearly $15 million to 108 scientists in an effort to focus worldwide scientific and public attention on cancer research. Thirteen previous winners have subsequently won Nobel Prizes.

About General Motors

General Motors Corp. , the world's largest automaker, has been the global industry sales leader since 1931. Founded in 1908, GM today employs about 321,000 people around the world. It has manufacturing operations in 32 countries and its vehicles are sold in 200 countries. In 2004, GM sold nearly 9 million cars and trucks globally, up 4 percent and the second-highest total in the company's history. GM's global headquarters are at the GM Renaissance Center in Detroit. More information on GM can be found at http://www.gm.com .