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Alumni Hall of Fame 2011
Ed Acton and his colleagues developed and demonstrated techniques for the synthesis of hundreds of new chemicals for screening as potential anticancer drugs. Activity and mechanism studies, beyond the National Cancer Institute (NCI) screen, were carried out in numerous laboratories. From 1959 until 1986, his investigations covered a wide variety of chemical classes and structures. With his colleagues, Ed wrote and published more than 80 papers and was issued 19 patents.
The quality of Ed’s work and the straightforwardness of his efforts brought SRI to the attention of cancer researchers around the world and brought a steady stream of funding to SRI’s Life Sciences Division, much of it from NCI.
Ed presented his findings at scientific meetings in North America and Europe, which led to useful collaborations between SRI and other research organizations. After Ed left SRI, he spent several years in Bethesda, Maryland, doing drug synthesis at at NCI.
Earl Blackwell began his career at SRI in the Huntsville, Alabama, office in May 1970. Three years later, Earl transferred to Menlo Park, where he took the lead on a program to improve the effectiveness of the U.S. Navy’s ICBM test and training ranges. In every program he engaged in during his career, Earl consistently contributed innovations that resulted in significant improvements in U.S. leadership in both the development of military systems and the training of our armed forces personnel.
Earl became well known and highly respected nationally for his development of systems to provide high-accuracy real-time measurement applications using the satellite-based Global Positioning System assets. One of these, Exploitation of Differential GPS for Guidance Enhancement, culminated over 17 years of research and innovative techniques that spawned a number of related projects. With Earl’s assistance, this program area continued to grow, diversify, and prosper and still is considered an important core business base for SRI’s Engineering & Systems Group.
Earl’s approach to new technical challenges was unconstrained and creative, enabling him to consider all potentially feasible alternatives while never missing the big picture. Earl’s professional and innovative approach is considered outstanding by all who worked with him—management, staff, and clients.
As a mentor and teacher, Earl developed SRI’s younger and less experienced staff. His ability to instruct through technical discussions and freewheeling exchanges always contributed greatly to the overall development of future project leaders while ensuring the best possible technical effort on the project at hand. Everyone on Earl’s project teams received an invigorating, creative experience that helped rapidly expand their systems development and engineering skills.
Joe DeGraw led a very extended effort at SRI on a class of cancer-fighting drugs that compromise a cancer’s ability to use normal blood constituents to grow. One of those normal growth-enabling compounds is folic acid. This natural compound is particularly important to rapid cell division and thus can be a “feeder” to cancer. As early as the 1950s, researchers synthesized a drug, methotrexate (MTX), that appeared to a cancer cell as folate but, once transported into the cell, caused its death through inhibiting its production of DNA/RNA. Thus this class of drugs was called antifolates, and SRI’s versions of these started with improvements to that line. One improved compound, edatrexate (EDX), was far more effective than previous versions in experimental tumors in animals. EDX has been used alone and in combination with other drugs for lung and breast cancer in clinical trials and non-Hodgkins lymphomas, although it has not been commercialized.
In the 1990s, Joe and his colleagues introduced another SRI analog, called PDX, that was targeted for smoking-induced lung cancer. Again, to help differentiate cancer from normal cells, it exploits a specific transport protein that is more abundantly expressed in cancer cells. Now known as pralatrexate, PDX passed through accelerated trials because of urgent need. It was approved in 2009 as the first drug available for relapsed or refractory peripheral T-cell lymphoma, a biologically diverse group of aggressive blood cancers that have a poor prognosis. It is on the market and also is under evaluation for several other cancers. Through the many decades of this SRI work on antifolates, Joe was the principal contributor.
Over his nearly 40 years at SRI, Joe also invented other antifolate drugs, including some for the treatment of rheumatoid arthritis. He also created a nonaddictive analog of morphine and even a pheromone to help control the western pine beetle that is devastating many western forests. And there were other leadership positions at SRI. From his entry as an organic chemist in 1957, he became a leader of SRI’s medicinal chemistry effort, directing that effort from 1974 to 1990 and then as Associate Director of Biorganic Chemistry until 1994. He was named an SRI Fellow in 1987 for his antifolate work and other activities, including the above-mentioned drugs. Joe was the author of more than 160 research publications and 30 patents during his career at SRI. He was on the editorial board of Current Medicinal Chemistry and served as a reviewer for National Institutes of Health (NIH) grant award committees from 1980 to 1988. He also served as a consultant to numerous pharmaceutical companies in the United States, Europe, and Japan.
As a group leader in the Life Sciences Division, Elmer Reist developed several long-running research programs on drug synthesis, starting with one for antiviral and antimalarial agents, supported by the National Institute of Allergy and Infectious Diseases (NIAID) and Walter Reed Army Medical Center, respectively. This program in nucleoside and carbohydrate chemistry drew on his 10 years of experience at SRI synthesizing anticancer drugs for the National Cancer Institute (NCI).
Elmer subsequently established a program to synthesize potential carcinogens for the chemical repository of NCI. In collaboration with several other research organizations, he even designed labs with special air handling systems to prevent the release of these carcinogens.
Another program Elmer developed prepared new chemicals to treat AIDS and AIDS-related side diseases, such as cytomegalovirus. It developed into a 10-year effort funded by NIAID and was carried out in collaboration with researchers at Washington State University.
Elmer’s programs brought renown to SRI and established SRI’s preeminence in the field of drug synthesis. With his many presentations and publications, Elmer became well known throughout the worldwide research community. At the time of his retirement, he was Associate Director of Bioorganic Chemistry and had more than 100 publications in peer-reviewed journals and several patents on antiviral agents.