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R Gn`1_...Iw i Yy!• a ~~ e t ts one oLth'a lowliest of nature's creatures.a rod-shaped beast te less than a ten-thousandth of an inch bng. Its normal hab- 37e itat is the intestine" Its functions therc are still hasically un _ knowri,"Ye['this tiny parcel of protoplasm h'as now become [he n(erofastottnycorttroversythathasdividedtheseientificcom-'"; ~ munity, dtirred fears--oRen farfetehed-about tampering wtth ~ pature• and raised the prospect of unprecedented federal and lo- >r 'cal controls on basic scientific research. Last week the bacterium known to scientista as Escherlchia coli• (6, colr; for shortl;even be } e ,'came a preaccupalionat the highest tevels of government. ~Appcaring before a-Senate subcommittee on behalf of the Crarter. Administration, HEW'Secretary, Joseph Califano asked.-p FCongress t0 impose federal restrictions on recombinant DNA re- X~•#~ai: search: a new form of genetic,inquiny involving E coJi: The ur .' ~ gency of Califano a'request underlined the remarkable fact. that c •p longtinie'dream of science,,genetic engineering,.is at hand ? ~and son[e fear already out of hand. In laboratories aeross the tion scientists are combining segments of E coi!'r DNA wtth. 7a,, We DNAf of planu• animals and other bac[eria By this process , ~ they tnay'.we6 beyc'reating forms of lifadifferent frovn any that . ~ ` ,yexist on eanh. ~ That this exctting new researchgolds great promise but could °s „: alao pose somc peril was stressed in the day-long testimony a: fore Senator.Edward Kennedy's health subcommittee. Califano TOFTWOE"COtIEXCNANG[NGGENESmIRWG""CONIUGATtON rny,' t, f, nlled recombinant DNA "a vientific tool of enormous poten- ' [iali • He also warned about possible-though unknown-har foreseeable nsks. What would happen, they ask, by accident ~ + ards and concluded: "There is no reasonable alternative to reg- or>iesign, one variety ofre-eagineered'E c+ofi,proved danger- . ~~ ?iilation under law.'.Massachusetts Governor Michael Dukakis. '{ait? By escaping from the lab and multiplying, their scenario ' involved in the controversy over genetictngineering prolects at goes it could find its way inlo human intestines and cause tmf Harvard and M.LT., argued for the public right to regulate th'e re- fling diseases. Beyond any immediate danger; others say, tltere search. Said he: "Genetic manipulation to create new forms of are vast unknowns and moral implications. Do not intervene in life places biologists at a threshold'similar to that which phys- svotution, they warn in effect, because "i['snot nice to fool Molh•- icists reached when they first'split the atom. I think it is fair to ter Nature," Caltech'3 biology chairman: Robert Sinsheimer, coti- ` « t• say thai the genie is ourof the bottle- ;-tat„ Oz Q! ~ cludes: "Biologists have become, without wanting it, the custo. +..~ ~ 'fhe issue, stated simply„ is whether that genie is good or . dians ofgreat and terrible power. It is idle to pretend otherwise:^ ~ ~~evil: Proponents of this research~in DNA-the master molecule =: •-.Thescientific tommuttityis bitterly divided about theun-~y of life-are convinced that it can help point the Way'toward a- known ruksofgenetic enginoering ihe wrangling has been pub- ~~ ~4 A.`fiew promised land-of understanding and perhaps curing can- Iic, and traditional scientific courtesy has all but vanished. In- . ~ cqcr and such inherited-0iseases as diabetes and hemophilia; of furiated by unrcasoningopposition to the new discovenes James ` ~. Inexpensive new vaccines;,of plants that draw their nitrogen . Watson-who, with Francis Crick, won a Nobel Prize for de- 11 ag~"~r d[rectly from the a'v rather than from costly fertilizers; of a vast- ' termining the double-helix structure of the DNA (for deoxyri- ly improved knowledge of the genetics of all plants and an- -bonuctei¢ acid) molecule-has labeled the critics "kooks "shib'" i[na(s, including eventually even humans (TtME special section, - and'"incompetents." One of his targets is fellow Nobel faureate l I A April 14: 14711 :~ rr~` '; ~ M*. r x'George Wald. who has supported efforts to ban tecombinantC W~ : t~pponents of the new 'research acknowledge its likely _ DNA research at Harvard and M:f.T. Wald' contends that in- r~batnty, but fear that those benefits might be outweighed by un- stead oftrying to findthe rootsofcancer, forexample, th:oughgo- ror F~ ~ _ N.rtud iti du~covere..theGerman ttdralncian theodor F~chericA. who uo M Inoantroa.teanrntassa~atar,utu ut teecdon +. 1sir.•A.i netic research society can fight the disease more effectively by i/V b ~' takin$ carctno ns outof the environment s ._Y.-. ~ . . , .- `.. .. . •~rt. . .. _. ..• . 34 tiME. Anxrt u. »n. -~ q Z "4:1 DOOMSDAY/COVERSTORY ® ® 0 0 0 ® ..r--r-4- ' P, . , s - ® ta./N - +r..k .~. ~ f S . 1ESEAlCIIE! WORKING W[TN EEfr ANIMA[S tN N16N{ONTA[N/4£Nr lM ;'„~: . e t. . 87 .. r ~ 0 ®

aking a Safer Microbe ~ ~e oaly mdication that the bug would tnake a poor pathogen, or disease or- :. ganism. Curtiss' handmade mierobe will not survive in human serum-including ~.y,,Labotatories can be designed to pre- mained DAPless. But move frustration that of cancer patients. It is also easi- vent the escape of potentially dangerous awaited Curtiss: the mutants managed ly destroyed by common household But there is always the to survive and multiply even without detergents. ince that something or someone will DAP. How?'Iknnis Pereira„a graduate Curtiss named his transmuted bug that a few virulent bugs will student who worked'with Cltrtiss on the E coli x1776-in honor of the Bicen- slip through the safeguards to multiply project, discovered that they were pro- tennial: In November 1976, the NtH cer- iu the outside world. Faced with this ducing a sticky substance called colanic tified it for use in genetic engineering problem at the Asilomar conference, 'acidthat held them together in the ab- '"ezperiments,,removing oneof the ma- Geneticist Roy Curtiss III proposed an sence of their normal outer coat By ma- jor obstacles to resuming recombinant ingenious solution: Why not convert the nipulating still another of the microbe's DNA research standard genetic research organism a genes, Curtiss and'Pereira deprived the , oEtrrncisr cuRnss IN tAaoaAroar ' Wain of'the colt bacterium into a se bug of its ability to make colanie acid -,-. riously weakened mutant variety that That change provided an unexpected would quickly self-destruct if it escaped dividend; it also made the already sick- the laboratory? Curtiss volunteered to ly microbe extremely sensitive to ultra- englneer the new bug, and his colleagues violet light. Any exposure to sunlight agreed to hold off on many of theu re- would kill it. combinant DNA experiments until'they After a few more genetic refine- could be supplied with itl a' 2- :-; ; ments, Curtiss had developed what Returning to his laboratory at the seemed to be a safe research bacterium. University of Alabama Medical Center But a major problem remained. Even in Birmingham, Curtiss quickly hit on dying E coli bacteria can conjugate with a way to keep E: codl undereontrol. The healthy ones, transferring their possiblyy microbes must be able to manufacture dangerous genetic material in the proa a protective membrane; without such an cess. Thus an escaped and dying bug outer ooat they would swell and bursr might still pose a danger. Again Curtiss during normal growth. To keep them worked his genetic magic, this time tak- from manufacturing a complete coat, ing away from the microbe the ability Curtiss created an E coli with a defect to produce the chemical thymine, which in a gene that makes diaminopimelic is a component of the bug's own DNA. acid (DAP); an importanCingredient of. Without lhyminesupplied in the lab, the the membrane. The defect made the E coli'could not pass its genes on to bugs dependent for their survival upon healthy outsiders. DAP supplied'by scientists. -- ' Curtiss is still working to develop a Unfortunately, the defect proved in- more perfect-or defective-microbe Ytcient. Some of the descendants of for recombinant DNA research, But for new microbe mutated naturally and the time being, genetic enginean have began manufacturing theirown DAP. So available a tailor-made microbe that Curtiss went a step further and'deleted cannot survive outside the laboratory another gene involved in DAP produc- and that cannot colonize or even live in 7 I tion. These newly designed bugs re- the human intestinal tract. Nor is this OK ~.nMt.xwn Is. ivrn 45 ~ r1; _ iing harmlesa bacterial genes into E cofi=to ultra-sectue laboratories ("P-4") ior~ work with animal tumor viruses or pri, cslLt. At present, two new P-4 facilities are almost ready. s a gleaming white trailer parked behind a barbed-wire on the grounds of the National Institutes of Health in Be- esda, Md. It has a totally sealed environment, airtocks, de- Most scientists breathed a sigh of relief; the specter of local tamination systems, showers for workers after experiments, ' governments proclaiming a hodgepodge of crippling restrictions ~ sealed oabinets accessible only through attached gloves. Some on the freedom of inquiry had faded-at least temporarily. Lo- case" experiments, involving animal tumor viruses, will cal politicians now may go along with the impending federal leg- in the trailer this summer. NIH is also converting some of islation, which is expected to impose restraints on all research- ;the abandoned germ-warfare labs at Marylhnd's Fort Detrick ets-including those at previously unregulated industry labs: Still. Into similar super-containment facilities. In addition to the labs, scientists remain concerned over any political controls on their Wegtudelinestrquire the use ofthe self-destructing, escape-proof work_ At last week's Senate hearing, these fears were voiced by . IDl_crobes for certain higher-risk experiments. : r, ' Norton Zinder, a molecular geneticist at Rockefeller Univer- 1Kost researchers, eager to continue their work in cracking sity. Said he: "We are moving into a precedent-making area genetic riddles, welcomed the guidelines. Numerous uni- -the regulation of an area of scientific research-and I must asitles across the country had already begun work on new P-3 plead that this be done with extreme care and without haste. hbs, which have a lower and less costly level of containment (air The record of past'sttempts of authoritative bodies, either church locks, limited access, safety cabinets with curtains of flowing air) , or state, to control intellectual thought and work have led to than P-4 facilities. Not everyone, thottgh, was pleased. ••- some of the sorriest chapters in human history." ;#'~~,;;a'~'+r x ftged on by Wald and his biologist wife, Ruth Hubbard, .-?,Zinder has reason for worry. But he and other sctentists Cambridge's Mayor Alfred Velluci used the escalating DNA fu- should find reassurance in the experience of Cambridge. There, to, badger his old foe, Harvard. He convened the city council citizens patiently ignored political i demagoguery, perceived the an effort to halt DNA research at the school. Said Vellucc,_ faL4e notes in the voices of doom, mastered the complex issues "Sotnethi.ng could crawl out of the laboratory, such as a Fran- and then cast their votes for the continuation-with reasonable Ioenstein." At the council's request, Harvard and M.I.T. agreed restraints-*f free scientific inquiry. Congress should do no less. r„` SCIENCE to a moratorium on P-3 research while an eight-member cit- iuns' review board'studied the issue. In February, the council overrode Velluci and passed an ordinance permitting recom- ..~ , binanti DNA work to be restuned in Cambridge-under stan ' dards only slightly more strict than the NIH guidelines.

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