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THE SCIENTIST® The Newspaper for the f.ife Sciences Professional Publisher and Editor-in-Chief Eugene Garfield Associate Publisher Alfred Welljams-Dorof Managing Editor Barbara Spector Assistant Managing Editor Phil Beck Senior News Editor Franklin Hokc Associate Editor Karen Young Kreeger Assistant Editor Neeraja Sankaran Contributing Editors Steven Benowitz Billy Goodman Ricki Lewis Design Director D. Joy Kerschner Display Advertising Representatives Diana Bonett Will Kuhlman Fran Becker Russo Classified Advertising Manager Jim Harvie Classified Advertising Coordinator Richard Tenaro Circulation Manager Phyllis B. Pritz Controller Robert G. Jordan Administrative Coordinator Lynn Gambale Editorial Advisory Board Joshua Lederberg (Chairman) Theodor Benfey Steven M. Block Baruch S. Blumberg D. Walter Cohen Carl Djerassi Roald Hoffmann David Kritchevsky Louis Lasagna Victor McElheny Zhores Medvedev Robert K. Merton Dorothy Nelkin William Nierenberg Arnold Thackray V'rrginia Trimble Home Office: 3600 Market SL Suite 450 Philadelphia, Pa. 19104-2645 Tel.: (215) 386-9601 Fax: (215) 387-7542 E-ma11:71784.2561 Ocompuserve.com \V/ rTreiwoui. September 4, 1995 THE SCIENTIST 13 COMMENTARY by Stanley Hattman DNA Methylation Society's Main Objective: Fostering Communication Among Scientists As scientific progress and information has exploded in all areas of biomedical research, there has been a concomitant proliferation of joumals. Keeping abreast of the published literature in all dis- ciplines, as well as communication of other useful forms of infor- mation, has been made more difficult by this proliferation. To some measure, professional societies could be more active in promot- ing communication among their own members, as well as to the greater scientific community. This is one important objective of the DNA Methylation Soci- ety, which was founded last year, with Melanie Ehrlich, a professor of biochemistry at Tulane University, as its first president. It is almost a half-century since the discovery of modified bases in DNA in 1948 and "host-induced modification" in 1952. Initially,- host-induced modification referred to a change in bacteriophage host range resulting from a single cycle of growth in a given strain of bacteria. Loss of growth ability, termed restriction, was shown to involve degradation of the viral DNA following injection into a "non-permissive" (or restricting) host. This fostered the notion that bacteria had the ability to confer, as well as recognize, "host specificity" on viral DNA. It was already known in the early 1960s that bacteria contain sequence-specific DNA-methyltransferases, which differ in their specificity. It wasn't long before DNA methylation was implicated as the primary mechanism for conferring "host specificity" to viral DNA. Later, it was shown that bacterial and plasmid DNAs were also subject to restriction-modification systems. These early observations eventually led to the discovery of "restriction nucle- ases," the sequence-specific endonucleases that are tools of the trade in all molecular biological research. DNA methylation is not confined to prokaryotes. In fact, it is univers8l in vertebrates and higher plants, often found among lower eukaryotes, and encoded by some viruses. Moreover, since the early days of studying host-induced modification, the number of systems has grown in which DNA methylation has been shown to play an important role in controlling some important cellular function. The examples include positively or negatively regulating gene tran- scription, maintaining X-chromosome inactivation in female mammals, directing DNA mismatch-repair, regulating the initia- tion of DNA replication, increasing the frequency of sponta- neous mutagenesis, establishing genomic imprinting, maintaining the normal number of chromosomes, and contributing toward car- cinogenesis. Only in some of these cases is the mechanism under- stood in which DNA methylation plays its role. Organisms that do not methylate their DNA probably use alternative mechanisms to achieve the same ends. Thus, the need for future investigation is particularly compelling. In fact, with the deepening appreciation of the biological importance of DNA methylation, there has been a growing number of investigators worldwide who have joined in research in this area. They represent a panoply of approach- es, from the purely biological to the bio- chemical and genetic to the purely structural. For example, the last two years have witnessed both the demonstration of a requirement for DNA methylation during normal embryonic development in transgenic mice and the first solution of a cocrystal structure of a DNA-[cytosine-51 methyltransferase-substrate complex. The lat- ter revealed a most surprising conformation of a reaction inter- mediate, namely, the first example of a base flipping out of the helix during protein-DNA interaction. As advances develop in a fast-moving and complex field, it is impprtant for workers to have the ability to rapidly communicate with one another. Promoting better communication includes the sharing of research and instructional materials, such as informa- tion about technical methods, summaries of papers and preprints, strains and enzymes, journal reference databases, and lecture notes. With an E-mail network, which allows messages to be sent to all members at once, members of the DNA Methylation Society have had lively discourse, most recently on the development of improved methods for genomic sequencing. The DNA Methylation Society, with more than 200 members, is open to all scientists who are interested in DNA methylation. We invite our colleagues to obtain more information about the soci- ety by contacting either me or Roger Adams, co-vice presidents of the society. I can be reached at the Department of Biology, Uni- versity of Rochester, Rochester, N.Y. 14627. E-mail: shat@modDNA.biology.rochester.edu. Adams can be reached at the Institute of Biomedical and Life Sciences. Division of Bio- chemistry and Molecular Biology, University of Glasgow, Glas- gow G12 866 U.K. E-mail: GBCA36@udcf.gla.ac.UK. In addition, the society recently established a World Wide Web home page (http://203.4.164.89/), featuring information and an application form. Stanley Hattman is a professor of biology at the University of Rochester. Letters Duesberg Responds Samuel Katz (Letters, The Scientist, Aug. 21, 1995, page 11) criticizes my proposal that AIDS is caused by recreational drugs, AZT, and other noncontagious risk factors for not discussing "maternal-infant trans- mission of HIV/AIDS." However, I have pointed out explicitly in The Scientist that about 80 percent of pediatric AIDS in the United States and Europe is the conse- quence of intravenous drugs received by newborns from their mothers prior to birth (P. Duesberg, The Scientist, March 20, 1995, page 12). The harm to these babies is often compounded by pre- and postnatal treatment with the cytotoxic DNA chain terminator AZT. This is documented as follows: 1. HIV-free children born to mothers who had used intravenous drugs during pregnancy have the same AIDS-defining diseases as HIV-positives (P.H. Duesberg, Pharmacology and Therapeutics, 55:201- 77, 1992), indicating that HIV is not even a "cofactor," as Katz suggests. 2. Upon termination of maternally transmitted drugs at birth, most babies recover from early "intermittent" AIDS- defining diseases and from T-cell deficien- cies and remain healthy for at least three (S. Blanche et al., New England Journal of Medicine, 330:308-12, 1994) to six years (European Collaborative Study, Pediatrics, 94:815-9, 1994), despite the presence of HIV f Only about 20 percent die or develop irreversible AIDS during the first year of their life, and most of these have been treated with AZT. Three indicators link their AIDS risk directly to the drug dosage consumed with their mother: (i) the "severity of the disease in the mother at the time of delivery," (ii) "children with drug withdrawal symp- toms" being at the highest risk, and (iii) children whose "mothers had used recre- ational drugs during the last six months of pregnancy were intermediate in their risk" (European Collaborative Study, Lancet, 337:253-60, 1991). 3. Katz asserts that my hypothesis that AZT causes AIDS is "refuted by the results of [clinical trial] ACTG076." However, ACTG076 demonstrated that matemal-infant transmission of HIV can be reduced from 25 percent to 8 percent with injection of the cytotoxic and muta- genic chain terminator AZT into 100 percent of pregnant HIV-positive mothers over six months and into the newborns for six weeks (E.M. Connor et al., N. Engl. J. Med., 331:1173-80. 1994). Regarding the clinical consequences, an editorial in the Lancet entitled "Zidovudine for mothers, fetus, and child: hope or poison?" worries about "long-term adverse effects" (344:207-9, 1994). A preliminary report mentioned "neutropenia, high bilirubin levels and anemia" (P. Cotton, Journal of the American Medical Association, 271:807, 1994). Another of Anthony Fauci's AZT trials on American HIV- positive children has been terminated because of AZT toxicity (L.K. Altman, New York Times, Feb. 13, 1995, page B5)-hardly a refutation of the AZT-AIDS hypothesis. According to a retrospective study on the toxicity of AZTto 104 fetuses, eight had to be aborted therapeutically, eight aborted spontaneously, and eight were born with serious birth defects (R.M. Kumar et al., Journal ofAcquired Immune Deficiency Syndromes, 7:1034-9, 1994). Psren Duesseac Department of Molecular and Cell Biology University of California Berkeley, Calif. 94720