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Pleiotropy: The Unmentionable Secret of Genetic Engineering!

Synopsis: Scientists base the entire field of genetic engineering on the assumption that one gene has only one effect—an effect scientists can manipulate at will. However, a disease epidemic in corn in 1970 proves that one gene can have at least two effects, a phenomenon called pleiotropy. The possibility of this epidemic was known for 8 years before the it actually happened. The US Department of Agriculture was organized to anticipate and prevent such a disaster. However, the system failed and the failure was covered up. Even today, a quarter century later, scientists are unwilling to discuss the possibility the corn fiasco could be repeated in a crop of such world importance as rice

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PLEIOTROPY? What's that!

The first great advance in the scientific application of genetics was the development of hybrid corn—providing the basis for the unparalleled productivity of U.S. agriculture. Corn seeds are produced by wind transfer of pollen from the tassel at the top of the plant to the female silk on each ear. Pollen from the same plant can fertilize the female part of that plant, i.e., corn is self-fertile. To produce a hybrid seed the pollen must come from a male parent which is genetically different from the female parent. The plants to be the male parent are planted in rows separate from the female parent, in a ratio of perhaps 2 male rows between each set of 6 female rows, The original production of hybrid corn required manual detasselling of the female parent, so that the only pollen was from the male rows. This manual detasselling provided summer employment for thousands of kids, but added a few pennies per acre to the cost of corn seed.

Then geneticists developed a genetic system of cytoplasmic male sterility (CMS) in 1948, in which the female parent produced no pollen. The kids were out of work, and scientific agriculture had begun! CMS was considered such a magnificent scientific development that, by 1970, the gene was incorporated into 85% of U.S. corn lines.

At that time, the USDA research leadership was organized into "investigations," each under a leader. This scientist-administrator was assigned the responsibility to identify coming problems and to pass warning up the chain of command to the Agricultural Research Administrator who would provide funds to meet any threat to U.S. crop production (1). In 1962 Philippine scientists sounded an alert for such a challenge when they reported that CMS corn lines were abnormally sensitive to the Southern Corn Leaf Blight (SCLB) disease. This warning was known in the US by the responsible leaders and government administrators, but apparently no research program was established to meet the challenge. (return)

In the spring of 1970, a major SCLB epidemic appeared in Florida, moving north and west as the growing season advanced. A billion dollars worth of corn was destroyed—the income, lives, and futures of many farmers. Commodities markets were in shambles. Experts feared that the 1971 corn crop might be totally destroyed, with cataclysmic effects for the US food supply and economy.

The investigating NRC (National Research Council, an arm of the National Academy of Sciences)committee (Horsfall committee) reported (2) the CMS-SCLB relationship, evaluating it relative to the Irish potato blight of the 1840's which killed and forced millions to flee Ireland. The Committee spoke out against genetic uniformity, and warned scientists against technology they didn’t understand. Thus ended what may have been the biggest genetic experiment ever to have failed. The affair is described in popular terms in a book by Doyle (3). Several USDA investigations leaders were members of the Horsfall Committee, including the leader responsible for corn. Although their report discussed organizational methods to avoid similar fiascoes in the future, they avoided mention of the investigations leader program or why it failed. That program, with the lines of administrative responsibility it established, was quickly abolished. (return)

The lesson forgotten!

The kids are now detasselling corn again. But in 1987 another NRC committee (Hess Committee) was charged with evaluating the newer techniques of genetic engineering and biotechnology. Members failed to discuss or even cite (4) the 1972 Horsfall report, effectively deleting the whole CMS-SCLB affair from the history of science. This omission permitted their glowing report that genetic engineering and biotechnology are THE future of agriculture, with no suggestion of any risk.

Corn was the first commercial crop to utilize a CMS genetic system. Onion was the second; carrot the third. As Leader of the USDA Vegetable Seed Investigations project at that time, I (Bruce Pollock) was responsible for a problem resulting from use of CMS in onions, and later encountered a similar situation in carrots. I was therefore perhaps the only person other than George Sprague, Leader for Corn and Sorghum Investigations, in a leadership role where the use of CMS came into question. At the time I understood that my status as Investigations Leader placed on my shoulders responsibility for public safety associated with problems in my Investigations. I still feel that responsibility. Unfortunately, George Sprague, because of the publicity from the SCLB epidemic, was trying to protect himself. (return to top)

I received an early copy of the Hess report and, shocked at the omission of the CMS-SCLB affair, requested it be rewritten to include evaluation of the significance of the SCLB epidemic and its genetic CMS cause in evaluating risks associated with the future of biotechnology. The letter of refusal (5), signed by Dr. Frank Press, President of the National Academy of Sciences, stated: "...there is no evidence demonstrating the gene responsible for male sterility...is the same as the gene or genes that increase the plant's susceptibility to the southern corn leaf blight pathogen...genetic engineering would lessen the chances of repeating the 1970's corn blight epidemic, since genetic engineering results in more precise genetic alterations." But Dr. Press was wrong! The 1990 review by Levings (6) shows that the same gene controls both CMS and SCLB sensitivity. Levings' review also provides the history of 20-years of research into the CMS-SCLB relationship, showing that the Press letter should not have been written in 1987 by a committee purportedly representing the highest level of US scientific expertise. (return to top)

Ignoring the Horsfall report and the CMS-SCLB relationship partially stifled public opposition and permitted the biotechnology industry to obtain financial support from stock sales to unsuspecting investors. An exact replication of the situation appeared more recently when viruses used to introduce engineered genes into human patients were found also to produce virus infections (8). One authority conceded: "...if the experiment had been done 3 years ago, we might have had a different timetable for gene therapy. Additional testing would have been required from the beginning."

Perhaps the most serious examples of concealing the history of the CMS-SCLB affair are two major books:

  1. A serious example of the scientific community's unwillingness to even mention any risk from genetic engineering is the evaluation of biotechnology (9) written specifically to "Provide information for decision makers." The decision-making population at which the report is directed includes legislators and other elected officials. This volume was published, using public funds, by the USDA and the Land Grant Universities, even though these agencies performed the research proving the CMS-SCLB gene is pleiotropic.

  2. The Rockefeller Foundation, the most important source of research funds for third world agriculture, is pumping resources into developing CMS for hybrid rice production. Their (10) Rice Biotechnology volume refers repeatedly to the successful use of CMS in corn production, but nowhere does it mention the CMS-SCLB epidemic or warn those interested in rice production of the danger of encountering a pleiotropic gene or repeating in rice the CMS-SCLB corn epidemic. Although fully aware of the CMS-SCLB history, Foundation administrators have adopted a "hands-off" policy which leaves any evaluation of risk up to the individual scientist. They do not provide him with the methods and resources he needs to make this risk evaluation (11). (return to top)

    Is there a "cover-up" of the CMS-SCLB epidemic? The question can be studied using the "Information for decision makers" volume (9) which discusses at great length risk evaluation and the necessity of information for risk evaluation. In presenting that information, the writers represent the hazards as theoretical—nowhere do they even hint that any model for these risks has entered into practical agriculture. Doyle has written an entire book based on the SCLB epidemic (3). The "Decision Makers" volume cites Doyle's book fleetingly in another context, but it's basis, the CMS-SCLB epidemic, is totally ignored.

    This omission of the existence of the CMS-SCLB gene cannot be attributed to scientific illiteracy. True, Dr. Press, over whose signature the erroneous conclusion about the CMS-SCLB gene was communicated, is a physical scientist who could not be reasonably expected to have personal knowledge of the details of a 20-year old agricultural epidemic. His personal illiteracy on this subject is excusable, although his responsibility as President of the National Academy of Sciences to obtain this information is inexcusable!

    However, Dr. Hess, chairman of the NRC committee making the error, was a practicing agricultural scientist at the time. When he subsequently became the Assistant Secretary of Agriculture for Science and Education, the highest US position in agricultural research, although he knew about the error, he made no attempt to correct it. Dr. Hess is coauthor of the final and capstone chapter in the "Decision Makers" book. Years after his original report and after being appraised of his original "error," Dr. Hess still has not acknowledged the CMS-SCLB epidemic. He was one of the leaders of the American Society for Horticultural Science (ASHS) at the time ASHS published the fraudulent papers by Bass and Kwan. Because of Dr. Hess' prominence in the scientific community, this history can only be interpreted by the public as proof of the "closed" culture of science. (return to top)

    If the CMS-SCLB episode was known to the public, it would undoubtedly strengthen opposition to biotechnology. The scientific community must face the serious scientific problems raised by the CMS-SCLB example:

    1. There was no way , by exercising logic, that the relationship between CMS and SCLB could have been predicted. The fact that a pleiotropic gene was inadvertently introduced into commercial agriculture, and remained in use for a quarter-century, means that the possibility of a repeat must be considered significant in the future use of any genetic material, no matter how valuable its other potential.

    2. Because it took more than a decade of commercial production before anyone recognized a possible problem; current government regulations for reducing the risk from genetically-engineered organisms are totally inadequate because they apply only to very limited time periods.

    3. It is impossible at this late date to explain why the USDA organization in effect at that time failed to function to prevent the 1970 disaster. However, the continued refusal of the scientific community to admit to its error means that any future method of providing public protection must be independent of the "scientific power structure" then in existence.

    BIBLIOGRAPHY

    (1) USDA Crops Research Division Leadership Requirements for Division Level, Branch Level, Investigations Level. 19p date about 1969
    (2) National Academy of Sciences (1972) Genetic vulnerability of major crops. (ISBN 0-309-02030-1) See also Tatum, L.A. (1971) The Southern Corn Leaf Blight Epidemic. Science 171: 1113-1116.
    (3) Doyle, J. (1985) Altered harvest: Agriculture, genetics, and the fate of the world's food supply. Viking Penguin, N.Y. 502p
    (4) National Academy of Science (1987) Agricultural biotechnology: Strategies for National Competitiveness. National Academy Press 205p.
    (5) Press, Frank, December 2, 1987 letter to Bruce M. Pollock.
    (6) Levings, C.S. III (1990) The Texas cytoplasm of maize: Cytoplasmic male sterility and disease susceptibility. Science 250: 942-947.
    (8) Thompson, L. (1992) Monkey tests spark safety review. Science 257: 1854.
    (9) Baumgardt, B.R. and M.A. Martin (1991) Agricultural biotechnology: Issues and Choices. Information for Decision Makers. Purdue University Agricultural Experiment Station ISBN 0-931682-82-2 180p.
    (10) Khush, G.S. & G.H. Toenniessen (1991). Rice biotechnology. CAB International, Wallingford, U.K. & International Rice Institute, Manila, Philippines. 320 p.
    (11) Toenniessen, G.H., letter to Bruce M. Pollock dated October 16, 1991.