Tobacco Documents Online

1000229663

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• stCLONING ' ~ ~~ ~ ~ Continued from Page ] e b~>~m~~ . ;.-: ., . And t}us is important Since time r,,,...' x; _. . immemorial, humans have been using f a~`e'~} the microbes - baeteria, molds and °~ ~ yeasts - to ferment wine, make bread and riperi; cheese. Worldwide, today. F3 -In microbes serve as miniature living fac- ~ ~~ ~~~~ t pories, producing dozens ot impo rodurts such as amino acids, enzymes, solvenu. pesticides, growth regulators and antibiotic medicines. ; Huge industries, notably the'phar- Y ~ By Robert Cooke Globe Staft ~ e4`~ ' Read or no at home and abroad, srtull new clonin : m'°ctutica] industry and brewing. have Y ~ 8 Mren built on the silent; uncomplaining `~ companies are springing up, scrambling to take advantage microbes. All these bugs require is good, of the hot discoverie; coming now frota the once-quiet realm foods, proper temperatures and com- of biology. fortahle conditions. ~~ Everybody - including major drug houses and oil com- The new goal' basically; fs to iede- , panies - is betting that the pay-off from genetic engineer- sign ttrrse living things, or build wholly ing is going to be btg new creatures that have never before W4 The gamble: That tiny microbes can be "engineered,"• been seen in nature. For example: "cloned"' their genes ritanipulated or .so they turn out large - Genetically engineered mit•rabes amounts of chemicals, hormones„ enedieines, vitamins and will one day be pouring out valuable foods on demand = a feat hvrmones for treatment of human ill- never before possible in ali of. ness. Already, at Harvard 'L'niversity, history. Walter Gilbert's reseaich=group has coaxed a lowly bacte?ium. E: colii: into making rat pro-insulin. Soon, this will • i be done with human Insulin, for use diabetic people. { ._ - At Cornell University, botanis.ts have found a way to swap genes be- tween yeast cells and other organisins, such as bacteria. 4'ltis opens the way for n of "tailor-made" ing eompan~ based it, liock p~uctio. types of yeast that will be important ~ in brewing, ville, Md. food processes baking and other . And in Europe, a group of leading 'scientists - •includ-' ing some' Americans. =. 'is putting '_ together a cloaing cornpany_.registered in Lux- emboutg -and based in Swit- `ierland. Thus lt's rlear that' busi= ness has seen the light• tn genetic engineering. :The'talk Is of cloning; but -•In this-easerloning has noth=- ing to do wittt making multi-• ple copies of Albert Einstein; ~•Idi" Amin.Dada or anyone- else. The work - for now, at least'- Is limited mostly to ° microbes, but in the future it will be extended to include plants and domestic animals. This whole enterprise turns on a few basic discoveries made in the last few years. The field is called "recombinant DNA experimentation,",but it means, basicalIy, that scien- tists now can swap genes back and forth among very differ- ent organisms. Genes are discrete units'made from a chemical called DNA, and represent nature s chemical codebook. They con- tain all the details on how to build and operate living organ- isrns - from men to microbes. Genetictngineering involves ckopping up and rearranging these chemical messages to yirld new, useful living things. . This has become possible because special enzymes have been found that can snip genes apart and splice them back togiether again in precise ways, allowing amazing flexibility in the construction of new organisms. .. . . . .. .. 1 _ . .,+a In Califoriiia, for • eicam= ple, two cloning firms •have been founded.• recently. In. Maryland, another smalll bio-' loginl research firm is nov.• building ,.Iaboratories -and hiring: scientists. In Michi- gan; a;" leading"biologist is now setting up his own clori- - Two resr.arch groups - one in - have Scattle, the other in Belgium found a way to introduce new genes= new bits of hered•itary fnformation"= into plants. This is through use of the bacterium that causes crown'gill dis. ease, a.,ty pe of, tumor ~ that , invoives insertion of new genes, in plants. If thii system proves useful,, the impact on world agriculture could beenormous. - New techniques for mating the unmate-ab1e,• cell fusion, also show promise. r lt ~:was snnounced,-slightly ; "- more than a•month ago, for example. that Otis Godfrey, of Eli Lilly & Co, had fused. two Streptomyces species to produce a new typp which makes an an- tibiotic' not- made by either parent ~. ' strain alone. " How fast, then; will results of such work be 'seen coming *from industryi Estimates vary, but most observers be- ~ lirve it will be less than 10 yearS. .' C Arnold L. Demain, professor of nu- :ritimn ~nd food science at MIT. has- tun~ had an interest in the use of mi- crr,he•s for pruduction of industrial products. He ct:rnmrntcd: "1 cxp~vt thit genirtic engineering. in tts brnade.t srnse, will be involved with indu.try within the next few v.,:m. Thi% is bec•ause there may be ww% to incrrese the gene dosage in rx- i.ting micro-organisms even without r.tinmhinant DNA" _fr,4d7~.3!F. L

NL'hr'.t this means is that-4t may be Demain'thinks it may be possible, «htle thc ftrms itrst efforts were c d h ntratt in t e pharmacrutical pr.sibte soon to dramatically increase using this kind of genetic engineering, cone induce bacteria to make the essential field, Cape said Cetus Corp. has recent the «mounts - or types - of products - t o _ : alrr+rd~• being m:~de by single-cell crea- amino acid tryptophan, the . vitamin `' ly bEgun finding customers In other uch as the foad h i d ii ; l - arrrs, s em .1 ca an o ~ tura•s• riboflavin, and biotin. a vitimin fed to " ~ : 'The first producu, Demain said, livrstock vl ill probably be enzymes, since busi- ~.. Prospects now look good enough. ncss is primed for this kind of activity. "The tryptophan operon has already ,• Cape and the president of Cetus, Peter Demain said J• Farlcy, saiii„so the dirnt has been rap- and because such enzymes are usually . been cloned in E. coli," ~ prodaced by only one gene." producing bacteria carryi, ' t; hundrrds ly hiring the best molecular biologists Important enzymes whose produc- of copies of the tryptoNhan genes, .. It can find. It advertised in Science tion might be enhanced by genetic rn- rather than just one set. Magazine. •got about 400 respanses, 4x; glneering include amylase,• which , In addition. Russian experimenters brought about two dozen to Berkeley a~, breaks dovn starches, and glucose "have taken the riboflavin cpemn from ; for IntervieM•s, and hired eight They ~:; Isomerase, which helps make the.cheap- a bacterium B. subulis and are cloning are still looking for.more. i h on to.t e new sn,all firnts ,~er, useful new high-tructose sugars• it in E. coli," but it is not-known yet if In addit .This rapid spaW ning of•new cloning . = rtootiavin ts actuany ocing mac „e ••r ' - arley nant DNA technulogy, Cape and l 'o " ~' *~~c ¢ mpanics may surprise somc pcople, main said. 't :: aid most of the dru and chemical ~` ~ g s , especii.lly thosc who watched the near- One set of genes many research companies have ezpressed •interest. A frantic?our- o er the safct c d b t d w ar y a v ~~ : e e get to ,. _,, y groups ould like to clone an couple dozen ehemical companies ar t ~ ''~ ' of genetic tinkering experiements• - working in a bacterium; Dema3n said, ls looking into it, and Imperial Chemical Now, however, some of those origi- the set that makes a biochemical called • - ' ' 6lreadyzn- " nal fears - about creating newplagues,_ Interferon. This natural substance ~?r Industries Engiand has is be- •nounced big plans"' d "M'hich is very difficult to isolate b t f fa . f , ou aew orms o t?erm vrar re an a , about rcirasing deadly new diseases by .'.Iieved to help defend the body itself `' against viral infections, ucident - seem to be subsidin , . rt g American researchers For a proposed therapy,' he said. Nonethelres %' Cetus Corp: itself has big pliris, es- ' pecially since two huge American cor- poratinns - Standard 011 of Indiana , _ who receive government funds, are still ou inust use human incerfcron. If we (Amoco), .and National Distlllers dr bought - substantial ,;.d required to observ r a strict set of guide- _ can do that, it.may be s: whole new ball w'Chemical Co. -l Iines-adminiatered by the US Nation- ; game in protecting us' against virss ,., shares, 25 and 15 percent respectively, diseases_. ' al Institutes of Health (NIH) -staUng •;r, within the last year. = what-th can do, what the cannot do `'•'' ` cY Y y, z- ... • Tliis; then, explains the excitement ~ ~ Their optimisiii. • Cape said, arises and how to do it. tp , found today among the world's major from •confidence'since "none of us It ls,thoiaght, however, tbat these ,: pharmaceutical companies, and It also - doubt the hurdies will'be hurdled. Our guidelines.vill soon be relaxed. ;yZ so _,~exPlains the rush to set up new compa f; purpose is to produce an economic bug and po'urs out ~ - nies to exploit these scientific discover . tltat lives on cheap stuff # The important point, however, is ~ 'n.vast quantities of a ptoduct.'.' ~. that these NIH guidelines do not apply to Industry, yet. And similar sets •of-- So far the most aggressive, mostad. .."tlie tvould predict -that. within.the guidelines overseas - where they exist. vanced of these new firms.. is Cettis -next.:ive or 10•years we re Qoing to see at all - are usually far less strict than • Corp.. M+hich'seems to have a five-to- biological involvement In tbe-produc- the American rules. seven-year head start in` the gasite. " tion of chemicalL that hatte • never be- ' •'Another interesting area ~ Demain . Cetus. Corp. Was formed •- wit4t fore been prvduced bioiogically: * said, "is the possibility of making vtta- headquarters Ih Berkeley. Calif.,-near "There's an•explosive new Industry c;;, ntins and amino acids by •these tech- ' the most famous campus of the Univer- here, no doubt about W We were the• niques. These are made by a series of sity of California -~,ust befQre new ex irst ones !n; we ve'got. a track record• _-genes, because they are~made by a se- ` periments witli recombinant;DNX'be- now,we've.gotour nomentum.lloweJ- . . . . . .ries ot eniymcs" : came pwcsiole- Its orrainal goal was to '.er that rnay contr•bute.to.4 1ead, we're Aa important point, 'he added, 'is take advantagrhf the growing.store ot Aoing to try,to maintain it bi l o that in some cases these.sets cf genes new kniiwledge in molecular ogy. - f' x' Simll:r optimisat is-?ound at are clustered together to form what Is, as applied to industry. ;..7 thesdb Research Laboratories Inc, of cal;ed an "operon," aad 'if it's.all to- . -Cetus was founded by -,or around ockville, Md, where 1Jr Patricia Berg gether on one picce of DNA, it's possi- - the inspiration•of Don Glaser. :vho has jusibeen hired as di ectorof genct- ble to introduce it into a plasmid. put it won the.Nobel Prize for Physics in 1960 ic engineeririg. " into E. coli and clone the whole for inventing the -bubble chamber" ° . oPeron" `- .'Cctus Corp.'s rhairmari, Ronald E. •'Our company 'is ree years old The lasmids Detnain mentioned are Cape, said. ~- < now, and it was found~1 with the idea P of making enzymes fo~'molecular biolo- one key element in this work. They are "Glaser movcd "away from physics gy. specifically >,~,e restriction fi d d C •to n- ttny rtngs of genettc matenal, DNA, into biology, and he v.ante r:h'ich are not part of the bacterium's ways to mechanize the hunt for-rare ns,rmal store of genetic information. ' evcnts in biology. It was our feeling. Plusrniils do, no..•ever, carry genes that back in 1971, that thvre must be prob- enabic the L•ecteria do certain jobs. lems in industrial microbiology that re- They are passh: around among bacteria quire this sort of screeni'ng:' Cape said. - in a procFss called conjugation - After a fe:v rougFi vears, and a tough, like so much loose change. timr cr~n~•incing industrialists toey Such plssnids normallycarry genes nerd outside help witn microbiu6+gy- for antibiotic rrsistance, giving bacte- Cape said, business has started taking ria the ability to outsmart antibiotic hold• and now •'our product is just im- mrdicines. But scientists have learned proving yields from biochemical prnc- to rnanipulatc this pl.cmid systrm and rsses. We're basically in Ihr business of w,- it to ferry ncK, abnnrnial grrottit• dev+loping biolosically-basrd induttri- in:v::r.ation tr+to microh•s. al processes. enzymes." "At present, we'rI~' just•considerinr various options" in g nctic engineering. "We haven't dccid wherr we're going yet, but we do exp t to have our labo- ratory functional b July 1. We're set- ting up a DNA res ,arch.group, and we now have about 25 em loyees," she said in an interview. For purposes pt comparison. Cetus, in BerkcJry, now has 150 employees, anei 40 of them have advanced degrees. Capa himself earned a Ph.D. in biulogy, then took a master's degree in business '-=;

:r,- adminutration at Iiurvard• Farley, who ' favY:Sd/ ~ie~"rhas a medical degrrr also took a .,' master's dcgrse in business,at Ston- ~` tord. Fvcn sntaller and newer - but also basrd in liiarylanJ -- is Genex Cur • foundcd under the guidance o r. a- vid Jackson of the University of 1Vlichi- gan. So far all they have Is the ottice. is^ : . a secrrtary and a presidentDr •. suite,,. 1li Glik l3ut Tenea too has plans .~scz.,, tvr cashing in on the industrial pros- s',:~~ .-~> „ pertsofrecomi,inantD?lA t . ~-• tRg Wc rc basically a consulting com- k= ~ =~tt pany to industry," Glick said. "We have T3' assembled a group of consultants'to t' GenaC using knowledgable people ~ ande one of Biugen s nine scientist co ,- `<from ail around the country So we're founders !s Dr Walter Gilbert of Har- . x. ,. •== essentially a general contractor Irt vard . genetic engineering.:. lt was Gllbert's group at Harvard ~ which recentl announced It has ~~ A:imilar approach to the cloning tricked the E coll bacterium Into mak- . ~., . business is being used by Genentech, -r tee Ing -- and excreting - the rat pro-insu. ~ ;_ another tledglin~ California company ~ . :. that is about to open its own loborator- lin molectile. ,, ies in South San Franciaco E~ So tai, Gilbert said, Biogen has no . ' .pcrmanen t facjlities ot its own, but it Unlike Ce.tusi Corp., which does all "I 4~ ts seeking some laboratory space in its own research •in-house. Genentech • witzerlatid• For now, the group qCscJ S asks researcher's associated with uni- qntiits'whodo the advising (for the ,• versities or private research centers tn cprporation) are beginning to do exper- -t" •take on projects, - Iments in their own laboratoiies ~ areas •of this T` "Genen{eclt provides the.capital for flne'of the stickiest dettined research; - explained the firra's' whole enterprise, however,•!s going'to patent counsel, Thomas Kiley;"It's just be'the tssue of patents. Stanford Un(= a matter Qtdevising a researcli proposal versity and the University of Califor- and then:.contracting the •research'to. nia, for example, have filed for a patent 'the institution.' c4vcring most of the experimental fech- ~Genentecn indeed wac the'sponsoi niques. Genentech, too, has filed a pat- ,, of pioneering research done at the Un!- ent on its'tomatastatin work, and Har~ California land the City off vard has iiow applied for a patent on versity of Hope in southern California which re Gilbert s results with lnsulin. ,,- suited in the first mamalian substance, There. is no answer yet, ?towever, ""`1n a small brain liormone - somatosta- whethcr thac new. types of living or- tin =. being made. by the bacterium E, ganisms are even-•going to be patent- >`oli:'The work was done iri the labora-• abia •:. -~-.. .., = According of Dr. Herbert Boyer at the Uni- ccording to Roman Saliwanchik, a versity of California, San Francisco.. senior patent attorney fo~~ the Uaiohn. Co. in Kalamawo Mich:; the position . Boyer, along with Robert,Swanson, of -the patent'office is that the Patent ts a co-founder :of Genentech. Boyer •Staiute precludes the patenting of liv-, himself has made some of the most im= Ing things. The seakon they've been pa- portant, discoveries !n recombinant tenting plants is that there is a special DNA experiments. Swanson, who has a patent law for plants." degree in chetnistry from MIT, also Upjohn won a favorable"decision on holds a• business degree from MIT. this issue from ihe US Court of Cus- The newly formed cloning company toms and Patent Appeals last October, setting up shop - in Europe is called Now the patent o#tice, through the gov- Bio en which was just recently incor- ernment,. has appealed that decision to porated in Luxembour • Its president is the US Supreme Court. A decision is a Nrw Yor businessman, Dan Adams, expected soon. F r?sE: *t,'"d ~ s sr =;•>t aA ~ .~ P*:aa %