Second oncogene linked to growth-factor protein In what is being hailed as "another leap forward in understanding the basis of cancer," an international team of scientists has uncovered a striking similarity between the protein product of a viral oncogene and a cell membrane protein involved in triggering cell division. The link suggests how a virus may be able to seduce cells into a cancerous style of growth. The discovery was made by Michael D. Waterfield of the Imperial Cancer Research Fund Laboratories in London; Joseph Schlessinger at Weizmann Institute of Science in Rehovot, Israel; Axel Ullrich of Genentech, a biotechnology company in San Francisco; and their colleagues. The latest news comes on the heels of related results, published seven months ago by Waterfield and another group, that the amino acid sequence of another protein that triggers normal cell division, platelet-derived growth factor, is almost identical to that of a protein product of another viral oncogene implicated in cancer (C&EN, July 25,1983, page 16). Such links now appear to be more the general rule than the exception. In the latest round of experiments [Nature, 307, 521 (1984)], Waterfield's
group determined the amino acid sequence of portions of a protein called epidermal growth factor (EGF) receptor. This protein is attached to the membrane of human cells, where it serves as a lock for the growth-factor key. When lock and key combine, a biochemical mechanism is set in motion, causing the cell to divide and multiply. By searching a computer databank of known protein sequences, the researchers found a close match between the amino acid sequence of EGF receptor and a protein produced by an oncogene called erb-B. This oncogene is associated with a virus that causes leukemia in chickens. Thus, it appears that in cells infected with this avian virus, the oncogene produces a protein that masquerades as part of the growthfactor receptor because of its similarity to that receptor. Significantly, the erb-B protein doesn't mimic that part of the EGF receptor that lies on the outside wall of the cell and binds to growth factor; it mimics only that portion of the receptor that is ensconced inside the cell. Thus, the erb-B protein, functioning as a defective impostor of the receptor, triggers rampant cell growth without being activated by growth factor. How it does this isn't known yet. •
Genetic engineering patent approval likely The Patent & Trademark Office apparently will allow most sections of a Stanford University patent application on products of recombinant-DNA technology developed by Stanford and University of California scientists, according to university officials, with some sections remaining under review. Originally, the application was tentatively rejected (C&EN, Aug. 16, 1982, page 7.) However, no official decision has yet been reached and, according to Katherine Ku, associate director of Stanford's office of technology licensing, "our feeling is that a big deal is being made out of nothing. We are not really in any different position than we have been." The story surfaced when the As-
sociated Press obtained a copy of a confidential letter Stanford sent to each of the 68 companies that have been licensed under the patent apprising them of progress on the application. The patent is for products of recombinant-DNA techniques developed by Stanford genetics professor Stanley N. Cohen and University of California, San Francisco, biochemistry professor Herbert W. Boyer. A landmark patent on the Cohen/Boyer process was issued in 1980. That patent has not been challenged. However, if the products patent had been rejected on the basis of the three issues raised by the patent office, the original process patent likely would have been in jeopardy.
Apparently, all three issues—that the process was insufficiently described, that the process occurs naturally under special circumstances, and that a coworker was not properly credited—have been resolved, Ku says. As such, the patent office intends to approve the patent for recombinant-DNA products from bacteria. The sections of the patent application that will remain under review concern applying the techniques in yeast. "It's a question of the scope of the patent," Ku says. •
Biochemist Meselson wins MacArthur award An illustrious career chock-full of scientific honors now has been capped by a MacArthur Foundation award. Last week, Matthew S. Meselson, Cabot Professor of Natural Sciences at Harvard University, was honored with a no-strings-attached, five-year $256,000 fellowship. He was one of 22 "exceptionally talented individuals," and the only chemist to be so honored this year. The MacArthur Foundation fellowships, which now number 116 for a total commitment of about $22 million, are given with no constraints. Their purpose is to free the fellows of economic pressures and to allow full rein for their creativity. By so honoring Meselson, the foundation recognizes his seminal and pioneering studies in molecular biology. In a scientific career that spans nearly three decades, Meselson has helped clarify the mechanisms of DNA recombination and repair. He was the first, for example, to isolate a restrictive enzyme and characterize its properties in biochemical terms. With a graduate student, he developed a mass spectrometric method for detecting low levels of dioxin. This high-sensitivity method is still the basis of dioxin analysis today. The foundation award also takes note of Meselson's unique contributions to the issues of biological and chemical warfare. Especially cited are his writings on yellow rain toxins in Afghanistan and Southeast Asia. February 20,1984 C&EN
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News of the Week
Meselson: great value of this award is that it can be used for anything Says Meselson, "The great value of this award is that it can be used for anything. I have to think very carefully about how to use it without using it for something that would be wasteful." But one thing he is sure to use it for, he says, is to present a paper to a meeting on yellow rain this spring in Ghent, Belgium. Also receiving a MacArthur fellowship is University of Illinois molecular biologist Carl R. Woese. His work on DNA sequencing has led him to postulate a third kingdom of organisms. •
EPA plans to revise air quality regulations While Congress continues its efforts to rewrite the Clean Air Act, the Environmental Protection Agency has announced that it is planning a number of changes in its air quality regulations. For example, the agency said last week that it is planning to rewrite national ambient air quality standards to regulate only particulate matter—smoke, dust, and soot— that is smaller than 10 microns in diameter. The current primary standard for particulates, designed to protect the most sensitive group in the population, limits the total number of large and small particles suspended in air as measured by a 8
February 20, 1984 C&EN
specified filter. But EPA contends that the larger particles are relatively without health effects and that the 10-micron limit will do just as well because only particles that size or smaller penetrate deeply into the lungs. The change could make it easier for some states and industries to comply with the Clean Air Act. However, because it is more expensive to control emissions of small particles, factories that emit them would face substantial pollution control costs. In a related move EPA disclosed that it would not include polycyclic organic matter (POM) on the list of pollutants covered by national ambient air quality standards. POM is a generic term that covers a large number of chemical substances containing two or more ring structures. They are generally produced by combustion, especially where combustion processes are incomplete. Major source categories for the com-
pounds include coke production residential burning of wood and coal; mobile sources such as automobiles, trucks, and aircraft; forest fires; and commercial and industrial incineration. It is well established, EPA admits, that extracts of particular air pollutants that contain POM are carcinogenic when painted on the skin of rodents or injected into newborn mice and that many are mutagenic in various tests. However, it says that the extent to which people are exposed to these compounds in ambient air, and hence the need to regulate them, isn't very clear. Moreover, EPA contends that the particulate standard and motor vehicle emission standards already are contributing to a downward trend in POM emissions. If further regulation is necessary the agency says it would be more appropriate to regulate the sources of POM emissions. •
Dual sites likely for international biotech center The long-drawn-out saga of where to locate the International Center for Genetic Engineering & Biotechnology (ICGEB) is nearing an end. The suggestion is that it be made up of two components—one in New Delhi, the other in Trieste. Approval is expected at a high-level ministerial meeting in April at the Vienna headquarters of the United Nations Industrial Development Organization (UNIDO), originator of the ICGEB concept. The latest proposal, passed by the preparatory committee, appears to be a compromise solution to an issue that has been the subject of intense debate and lobbying for a number of months. Few have argued against establishing such a center. But where it should be placed had become a matter of contention. Last fall in Madrid, where representatives of 44 countries spent two days in a nonconclusive debate, the belief was expressed that since ICGEB will be geared toward the needs of developing countries, the center itself should be located in such a country (C&EN, Sept. 26, 1983, page 14). The Indian delegate pushed hard for New Delhi even
though this ran counter to the recommendation of a committee of experts that UNIDO had selected to evaluate in detail the locations that had been put forward. India has offered $19 million to fund ICGEB; Italy, $37 million. Unclear at this stage is whether the money will be pooled and then redistributed between the two component laboratories or whether the Indian contribution will go toward New Delhi, and that of Italy to Trieste. Also unclear is the mechanism whereby research will be coordinated to avoid duplication. The other countries that also had offered to host c o m p o n e n t s of ICGEB—Egypt, Pakistan, Spain, Thailand, and Tunisia—might be given affiliated center status. Affiliated centers, UNIDO suggests, will be able to participate actively in ICGEB's training, research, and development activities. In 1981, UNIDO proposed setting up ICGEB to promote international cooperation in applying new genetic techniques toward meeting the practical needs of developing countries, and to encourage creation of national laboratories. D
