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`Improved strains of bacteria and other microorganisms are turning out a surprising ~svariety of commercial products ~ and they never complain by Gene Bylznsky ''' Since the dawn of history, man has been using micro- organisms such as bacteria, yeasts, and molds to ferment wine, leaven bread, ripen cheese. The discovery of ant'i- ,>.: K-'bi ti d h t i thi i o cs opene a new c ap er n s anc ent story and , today microorganisms are used as miniature factories to ~fmanufacture dozens of commercial products, including ~o amino acids, enzymes, solvents, insecticides, and plant- ~;~~ growth regulators, as well as numerous antibiotics this may prove to be only a beginning. We stand at the threshold of an~enormously more sophisticated exten- ".'sion of industrial microbiology through genetic upgrad- ing ing of organisms. As scarcity of other resources pinches ~ more an& more tightly, microorganisms-able to thrive .on cheap nutrients-will be called upon to yield an ex- '..: panding list of products, including fuel. A`~;`•`'"~ The special usefulness of microorganisms derives in ; part from their remarkable ability to synthesize complex compounds. It would cost too much to manufacture anti- biotics biotics by chemical synthesis, for instance. In the words 2fof Carl Djerassi, professor of chemistry at Stanford and head of Zoecon Corp.: l`One of the unsolved problems in }: chemistry is to mimic in the lab the incredible facility and `ease with which nature puts highly complex molecules '. ,together. We synthesize them in a pathetically difficult way, step by step, one amino acid at a time. Nature does it like a zipper." There is no universally accepted scientific term that covers all microorganisms. Some scientists like the term "protists" (from the Greek protista, the very first). Some ~ .. use "microbes." To lay:men, the w.ord' "microbe" is likely ~- to suggest a disease germ, but among scientists it pretty much serves as a shorter substitute for "microorganism." Research associate: Bro Uttal ~ Microbiologists often refer to the creaturesthey'stu g as lfbu s. s1_ ~'-`By any name, microorganisms differ from other living :things in the relative simplicity of their biological or- ' ganization. Many consist of a single cell. Even the multi- cellular ones do not display the differentiation into dis= .;tinct cell,types that typifies higher plants and animals.-' °,~!' While a microbial cell is simpler than a mammalian ' cell, it's still exceedingly complex. It can produce more than a thousand enzymes, those busy catalysts of cheiri-_ ical reactions, and it can juggle hundreds of reactions simultaneously. At any one time, however, much of the cell's enzymatic machinery is kept in reserve; only enzymes needed at that particular moment are produced. This versatility enables the microorganisms to respond to a change in nutrients with start'ling speed, in thou-" _'sandths of a second. Because of their great adaptability,~ y many microbes can live on a wide variety of organic materials-a great economic advantage, of course. `~~ . r ~ .. . .. ~ ~ ; + t i, 1 ~ n , . , : f : . ~~r~~Te?!aa`A-ST4:~: The best microbes are freaks v: ~Ar ;s it processes the nutrients, the microbial cell turns out metabolites, or end products of chemical reactions.(See diagram on opposite page.) Biologists draw a basic' distinction between primary and secondary metabolites. Primary metabolites are essential for the growth of the -cell; they include building blocks of proteins, such as' amino acids, as well as vitamins. Secondary metabolites are not necessary for the organism's growth, but may be helpful to it under some circumstances. Antibiotics fall into this category. From man's standpoint the ideal microbe is a freak- a wasteful one that produces an excess of some substance

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® ® t i 4 { > .OS. FOBTVHE'FeD•.ery.i>7i w t ,_..nT._.W. M;that has medicinal.or:industrial value. Microorganisms. ,aare-equipped with elaborate metabolic control systems ~ that signal when to stop making a particular subtn sace ionce the cell's needs are met„Microbiologists try to break __Better Mtcrobes % do~r.n ol ,bypass 8uch, Cont1-ols 'Io,get organisms to do ~.y s2 ichat he wants, t2ietisctenttst engages in a process that wsts Professor :1t nold I..: Demaimof li.I-T- calls "a battle of I.ioshua Lederberg torty eighs a .)iits bet%`.'een rtlierobe, and, microbiologtsts ~ a~~;.~,~ ~g~ba1 prue pe teuc st now at S:an= ~ , "~ a7prd Gniver'sit~ itas'done tronher ~ ~ sTf nti1 t1te,1940's, effortc tp make_ microot gantsms pro s onl.no,v mocrocrganisms ¢ x rx , '~ti a ng e ange benetw intoFination.'47h'e fridings are nc.r b ginnino tpo prove' ~ eful i in ind~uur~ m'qroqiol Arnold Demam forty-six a micro-' ~ uce in the desn•ed .vay concisted mainly of changing the ~q2~ntitrrents; 'aerattng• the ,fermentation, and mamtaining a~ 9apropet acidity The ptincipaj«ay,of',locating ne«• pro- " 30~T• . . . . . . ~td'# ductton organtsms.nvas to,screen for naturally occurring ¢_mutant colonies t.hat dtH'ered in color or shape from "nor "%t> otogist at M.I.T., and a former re- ~~'~ ' - - '- " f earch ~ executive at Merck,'4g`a ~~ ~b:mali',sti•ains. Researchers w_ouldd then expose the newly ~reader, in the development of so- na "discorered mutants to a variety of growth conditions to _;tlphisfieated genetc and biocnemi- ^~I-1?tascertain the optimum environment for the production of 't cat techniQuesbor modifying micro- ,~ ri~he:desired substancen~or{ti•'' organi<ms. Amomg other thmgs, he _.zis noted for studies ot factors {hat'tit, .. 4;;MUch more sophisticated manipulations began in the make some' micro5es better 'pio- jw ; early 1940's when scientists applied X rays to turn out a ; , itucers of anti5iwics than others: s~lg,~;,,superior penicillin-producing mutant of the mold Peni ;'`s4l.'., ciliinrn c1u•psoperitwn, (The ancestors came from a moldy ~ .};cantaloupe that a sharp-eyed researcher picked up in a (Peoria;,Illinois, farm market-) When penicillin was :first `~;; '~ :rprodd in thhl p uce laboratories,ere was rougy oneart per million in a t' ypica] fermentation broth (the nutrient medium in which microorganisms work). The deliber- ately pt oduced mutants increased penicillin output more ~3than a thousandfol~ ,Tractng the pathways ~$Y~:.:The 1940's sai. .the onset of a great wave of reseaiich .,dr+.c>,on!the structurej--'functioning,.-and geneticmakeup, of y.r. }rf t. microorganisms. Of particular interest to industrial ~< ~~ z;~ microbio]ogy a-as the develbpment of techniques for ~jd'entify-ing mutants with changed nutritional needs and r„~t:ytllus different end products. Later on, scientists pains- ~:rrtgiaakingly.traced the intricate metabolic pathways of ~, t•,,mieraoraanisms, and the enzyme sensor systems that ';6:r;-enable them to respond so flexibly to changing nutrient ;r conditions. The knowledge that gradually emerged en- abled industrial scientists to begin manipulating micro- „n ;i organiFms much more efficiently. Now they knew which •.buttons to press, as it «•ere, to make the microbes yield -a,? , a desired product. . , Tt . :f;t;The Japanese, in particular, were quick to apply these ;s,I• ,•findings, to industrial production. In one outstanding y,= aehiet-ement„ Japanese scientists developed a superior producer of lysine, an essential amino acid that the human body does not make but must obtain from food: With the help of such cooperative microbes, the Japanese ;,_; ,;built up the world's largest amino-acid industry. That ~ro~•ed to be a foresighted thing to do, especially in the C 7ight of worldwide protein shortages. Lysine is now added 3-,,.to animal feed and is beginning to find its n•ayint'o human yy7f 1 food too. Demand outruns supply. Says Bernard Wolnak, ~~~ F A- Hsmso Umezswa tiTty nme has aF discovered a number of medremal. :.-. substances manufactured by.micro- Organisms Among them are com- '~,pountls that show promise In the ~;;~ueatment,ofhigh blood pressure, "itomach ukers, and cenaiA infec- ~ `, . - tLons resistant to ~ amibiotics: , Ume- `': zawaa who was instrumental in !:~•buildi'ng up Jaoanese production ot ~L antibiotics, is tl~tediscoverer otf sev- ~ eral new antibiotics himself. 5 . Y i Y~s 9 0 j , ._ \.;. 6 0 ® ® A 4 0 t* 9 m r ~3i''o. -r...°_ T Y.! Y r.:;.

~t David A...Hopwood,.forty, a Britis6h genet cist, has concentrated on aF tering microorganisms through such novel lechniGuesas transler of. "plasmids'• (small genetic elements not contaihed ihi chromosomes)I from one species to another. David Perlman, fiftyrfour;.; dean of the school of pharmacyy at theUni: versiry, of. WPsconsin, works on mioroorganisms that have not been previouslyexaminedfory antibiotic activity. Finding new sources of antibioLcs is important, Perlman obser es, because only about one '.. newly discovered antibiotic in a: thousand wirds up in clinical use. Arthur Humphrey, fortyrsiz, dean -r~.of. engiireering at the Universityy o4 ~ . Pennsylvania..has pioneered in ap- plying computers to the control of : fermentationprocesses in industrial~ 'r,, '`'a Chicago-based consultant in industrial microbiology: "If I had ten million pounds of lysine today, I coult~ '1 ' it immediately." ` "' To improve microbial, production ofisecondary metab- "• blites such as antibiotics, industrial scientists are begin- " ning to employ the highly sophisticated techniques of ~ genetic engineering. Relying oni mutants with altered appetites doesn't work as well with secondary metab- olites, because not as much is known about their meta- bolic pathways as about' those of primary metabolit'es: I ~ Furthermore, some strains of antibiotic-producing bugs have been mutated many times by radiation and chem- " ical techniques, and apparently there are limits to how ' much ~further they can be improved by those methods. Accordingly„many, scientists see an important indus• , 'G° trial role ahead for the powerful new methods of trans- ferring genetic material from one cell to another. With these methods, scientists can employ transfers of llNA, those master molecules of life, to improve the production capabilities of microbes. Indian scientists transferred DNA from~ one antibiotic-producing species to another, which then began making both antibiotics. Soviet seierr tists imparted the ability to make streptomycin to a bug I that previously did not make that antibiotic. Some of the i ' new strains synthesized more streptomycin than the . donor microbes. :• I • Maps of the unseeable 1 So fat;,however„the use of sophisticated genetic engi- neering in the drug, industry has been onHy sporadic. A major reason is that locations of specific genes in indus- "trially important microbes remain largely uncharted. Y""Linkage maps," which show the arrangement of genes '` in a' chromosome, allow scientists to predict outcomes of 'genetic recombinations with a reliability that is impos- sible without the maps. But industry has shied away ` from the advanced research involved in genetic mapping, while academic scientists have concentrated on micro. microbiology. He is among those who advocate extensive use ofmi- %, croorganisms to consume pollutants and~to produce methane for fuel. organisms that are convenient to work.cith~butmay not be of any great' industrial importance. Now, however, efforts to map'some indUstrial microbes are under way '`'at Upjohn, Pfizer, and other companies. . The outlook for industrial microbiology has been = brightened by the development of new, technology for rapid, automated screening of' microbe colonies. (See `- box, next page.) This new technology, replacing the tedious eye-and-hand mutanthunting still commonin the industry, will greatly facilitate the search for mutants with desired characteristics. There is need for ne.v or improved antibiotics evem though more than sixty antibiotics are being manufac- tured in the UiS. today. Some disease-causing, microbes have developed resistance to the older antibiotics:& organisms, such as fungi;, have never been successiann= attacked with antibiotics, and new substances may be effective against them. Patents on many antibiotics have : :a+.+l jr.., . FORTUNE feDrwry.1974 99 1...- q ~. q 2. W.-. 3

~ .~ . ~ ;' 4 been expiring, so it is important for the companies in- ~ voh•ed to increase yields «-ith more efficient bugs so as t co maintain market shares. " Advanced methods for altering and selecting microbes will' also find applications in another important field of ~; industrial microbiology-production of enzymes. Indus- tryis making more and more use of microbial'enzymes as" chemical reagents. Whereas synthetic reactions often re-. quire high t'emperatules and pressures, microbial en~ 'iym off thtdtgf di th jbd ` esere grea avanae oongeo uner room-temperature conditions Arthur E Humphre3 .., ,a- :;ty hs Fe p~ ~ dean of engineering at the University of Pennsylvania ~ Fa , r;. yst€i + redicts that p' i oducti~on of such enzymes "will surelY be- p come a multibildion-dollar industry in the 1970's." 7i~ ~ M a y, A new source of energy t:,In addition to enzymes, antibiotics, amino acids, and a Farietyy of chemicals, microbes may be providing signifi- caiit quantities of fuel a few years from now. A little- exploited source of microbe-generated gas has long been available-municipal and industrial sewage-treatment plants, which use bacteria to consume wastes. Dlethane. (the principal component of natural gas) is generat'ed' in the digesters, and some large sewage plants may soon start selIinggas to utilities. ~*r-A novel way of using microorganisms to produce gas - has been developed by sanitary engineer W.J. Oswald `Lnd biologist C.G. Golueke of the University of California at Berkeley. Blue-greeni algae, single-celle& microscopic plants that efficiently convert sunlight into cellular energy, are grown in ponds, along with bacteria. The bacteria decompose sewage effluents into carboni diox- ide, ammonia, and other nutrients. Algae utilize these nutrients in storing solar energy in their cells. The algae are then harveste& and placed in a digester, where they serve as nutrient for bacteria. Anerobic fermentation in the digesters produces methane. Incompletely digested nutrients are recycled to feed algae and bacteria at the beginning of the process. The two scientists calculate that byt'heir methods elec- tric power could be generated for 10 to 20 mills per kilo- watt-hour. This is about twice as costly as conventional electricity production, but presumably large-scale opera- tion together n•ith~ refinement of techniques could narrow the gap. Other scientists are working on getting microbes to produce nitrogen fertilizer. Actually, they produce a lot'. of it already, with no help from industrial microbiology. Countless billions of microorganisms in the upper layer of soil absorb an estimated 100 millioni metric tons of nitrogen from the air each year and convert it into am- monia, a form of fertilizer. That is several times more 7han what the fertilizer industry turns out. - In efforts to improve on nature, bacteriologist Winston J. Brill and his associates at the University of Wisconsin recently succeeded in producing a bacterial mutant that' A.:. ~, ._. L'nusual numbers of v isitors have been trekking in recent months to the labora- tory of Professor Donald A. Glaser on the Berkeley campus of the University of California, They go there to examine ? •, a Glaser invention, deceptivelyy dubbed "the Dumbwaiter," that may enormous - ly expand the horizons of microbiology. , , It is large in~ bulk as well as in impor, • i. tanee. When~contpleted later this year, it will, be forty feet long, and two stories J high. The cost, about $2 milhon;`is being _~ ~ met mainlg with funds from the \ption- a] Institutes of Health, + ~ Already functioning inpi=ototjpe_ form, the Glaser apparatus is designed : to process 100 million microbial cultures at once, subjecting them to automatic surveillance and screening, in ',accord- ance with instructions programmed in a computer. This automated scanning will eliminate much of the tedium involved in microbiological investigations. Rapid processing of microorganisms.is impor- tant, moreover, because mutations of interest to science or industry occur quite infrequently. The faster research- ers can process large numbers of micro- organisms, therefore, , the 'better the >°-: chances of discovering mutants with sci- entific or commercial value. Dr. Glaser's ' Smart A science-fiction touch The basic elements of the machine are 956 glass trays, arranged in two stacks. The microorganisms are placed on a s,ol'. id'nutrient medium that covers the glass tray. So precise are the mechanisms that a single microorganism can be placed on a nutrient area to grow into a colony. The frames containing the trays move past various stations. The moving trays are photographed, and the film is exam- ined by a televisionlike camera linked to a computer. The system is programmed t6 find and count all the microbial colo- nies, to measure their diameters. and to characterize their visual appearance. It is also programmed to dose the colo- nies with~ nutrients, drugs, and other ~

':s. ~', id<h i I {il: chemical agents. One science-fiction Last year Cetus began upgrading the e~ ~ touch is a, aet o1 400 elegantly slender production qualities of microbes that 'f . ~ tq;:quartz "fingers" that can pick out mi- ,, belong to major drug companies, inelud- `^. t f:~crobes from a specifiCcolony and trans ting L'pjohn. The "bugs," worth millions`~~ ~~ ter them to a new environment l~ •,to theiR proprietors, are kept in deep- ~ ~ 'ireeze vaults under heavy electronic ' , Mlugs under electronic guard 'guard. Cetus plans to start work soon on ~ ` .04 ~;"The Dumbwaiter's sophistication has recombining genetic material in such,_ ~t aireadyy inspired one industrial system,„ microorganisms, andithe ability to proc- aI,nt - ~ i't is the property of Cetus Corp:, also ` ess large numbers of microbe colonies' ' 4located in Berkeley. In addition, a num- rapidl,v will undoubtedly be, of great -- ber ofl big' drug companies appear to be ., he1p. The company also expects to be able `~~~lrying to imitate the Glaser machme for '~to des•elop new microorganisms tailored `~ ' '. ~ thetr own use." tF 1•~tt~~ 5 F to do highly specific jobs, such as con-1-i- Kr '~i Convinced that the merging of molec- ' suming oil spilled at sea,'or to turn'dut a t~ulabiol and advanced technology rogy , ~0'~~can greatly increase industrial use of t ~j~il. ~nicroorganisms, Glaser has become chief "'scientific adviser of Cetus Corp. But the 'thardwat7e and'techniques being used by ~Cetus are quite unlike those of the Dumbwaiter. Another famous scientist 'iy;>linked up with Cetus is geneticist Josh- ~t' ~r aa' T..ederberg: He had long tried to inter- est'drug companies in the possibilities of, a:;''genetic engineering of microorganisms, ~and now Cetus expects to'put some of i'his ideas into practice.'Also, associated Ox`V9ith Cetus,"as directors•and financial Ifl'ttackers, are the notable"scientist=entre- `~?''preneurs Carl Djerassi and Alejandro Stj 'Zaffaroni, the ehief, executiti'es respec- !-~Y'tneh of Zoecon Corp' and Alza Corp :~~zt~.3xKr ~i. itkrCDonatdA.Glaser ~f-~z~'(ak*~tesr ~"nr { ,r, i )Y. ~ k © ® . . .. . .. ~.' _. . - . f. ~;~. . • brand new commercial products. As one . possible strategy, Cetus may sell super- : bugs itdevelops4o the highest bidder. ~ ,; ,~ „~^s 3 ' Frustration, mothenof mvention =?a'; Professor Glaser's Dumbwaiter is the second major invention he has contrib- uted to science. In 1960, when he was ' only thirty-four, he received the Nobeli Prize in physics for inventing the bub- ble chamber, which records tracks of elementary particles. Glaser built the bubble chamber because he had become frustrated by the limitations of' its pre- `; decessor device, the cloud chamber. His device made major advances possible. : Millions of eolonies ot microwganis Like several other outstanding minds ,; growing simuhtaneously in this stack of g ass . in the physical sciences, Glaser switched , t arays. The upper picturee shows a small portion in mideareer to molecular biology, with of one tray: Each of the circular areas is a its fascinating expanses of unexplored colony-most with a red center of older cetls., territory. Again;e heencountered tech '• surrounded bypale younger cell4 -.i nj Y •78•F rT ; t r~ jv • ¢a ,?~'t notogieal frustration. Trying to gain :1'~ 6 L r better insight into evolutionary mecha 7''i1a ~,iler? j r;e?i~v'n r'L s nisms in bacteria, he grew increasingly "'foodi water, air; or soil. Such microor- irritated with the slowness of the work. ganisms can often be identified from Vast numbers of culture plates had to be ' the distinctive appearance of the colo- laboriously processed! by hand. So in nies they form when they are grown in 1965 he began developing what came to a nutrient medium. be called the Dumbwaiter. ;+ .f'IFji'• With it's, capability for tending and A national scientific resource scrutinizing huge numbers of samples, Recently, Glaser invited a large num- Glaser's apparatus can do a variety of ber ofbiologists to use the Dumbwaiter, jobs besides looking for microbial mu- . not only for research in microbial gene- tants. For example, it should be useful tics but also forr work.vith cells of~higher for the study of behavior' and learning plants and animals. Animal cells can be in simple organisms. A candid' camera ' made to yield medically important hor- could' observe enclosures in, which in- mones. Single plant cells can be modified sects, worms, or other organisms were " as if they were microorganisms and can moving about'and record visible respon- then be used to grow complete plants sea to stimuli''such as,heat or lighti The ' with altered characteristics that pass on precision controliof environmental con. to succeeding generations. ditions would hel'p scienysts identify ...• , The Dumbwaiter, in short, is likely to genetic components of behavior. become an important' national sciC'Sc The Dumbwaiter can also be used to , resource. Clearly„it is to be hope..at automate medical tests, or to detect and Professor Glaser will encounter addi- identify contaminating microbes in tionalifrustrations during his career. s. .d i - .. .. . ,., , s- . , w s'~'ti rr' c : A FORTI.'NE FeWuary 1974 LOI , T : s,~

contiibues to convert atmospheric nitrogen into ammonia r egardless of the presence of related substances in its '`-surroundings. Normally, the presence of even trace amounts of nitrogenous substances close by will inhibit soil bacteria from~ producing ammonia. Colonies of the new mutants could be released to enrich soil, or they could. be employed to make ammonia in fermentation vats. The promise of "single-cell protein" "All of these various commercial uses of microbes have a common element : in each of them, in one w•ayor another, the living organism serves as a producer, a kind of fac- tory. There is another entirely different kind of com- mercial use, potentially more important than any of those described so far. In this case, the usefuli product is not some metabolite of the microbes but the microbes them- selves-instead of employing them as production work- ers; you eat them Microorganisms offer high protein content, and the protein does not differ significantly from that of other plants and animals. Microorganisms, moreover, are ex- ceedingly efficient producers of protein. Whereas it takes a 1,000-pound steer twenty-four hours to produce a pound of protein, 1,000 pounds of high-protein yeast cells grow into 4,000 pounds during that same span of time. And eating microorganisms is nothing new. For ages,, ir -leople have consume& yeasts, which are single-celled %.plants, without ill effects. .I~'ithin the past decade or so, oil companies have been conducting research on~ the use of petroleum fractions as feed for edible yeasts. The leader here has been British Petroleum, along with its French affiliate, Societe Fran- caise des Petroles B.P. The project began alrnost by accident in the late 1950's, when British Petroleum was seeking a way to de-wax heating oil to reduce its vis- cosity. Scientists at the French affiliate found that a type of yeast called Candida did the job. They also found the yeast cells to be extremely high in protein; Since then, B.P. has poured a lot of resources: into de- veloping, what is notivw known as single-cell protein-a term invented at M.I.T. The new protein was exhaustive- ly tested on various animals, and found to be both safee and highly nutritious, before B.P. began marketing it as a feed supplement in 1971. It contains as much as 66 per- cent protein by dry weight and more amino acids than standard protein,feed components such as fishmeal. Imperial Chemical! Industries Ltd. uses a different process to arrive at a similar end product : it raises bac- teria on methanol, which it derives from natural gas from the '.North Sea. Like British Petroleum, I.C.I. is ex- ceedingly optimistic about the future. Both companies envision big single-cell-protein plants dotting Europe, lnd later the developing nations. Alfred Spinks, research~ ~ director of I.C.I., predict'sthat the single-cell-protein~busi- ness could in the long term "change the shape of I.C.I. to a considerable degi ee" ; it might eventually account for 4 30 percent of that huge conapany's business. The protein plants could be built in conjunction with oil refineries. According to British experts, all of the , 'world's protein needs could be satisfied witlr utilization ~-N of only 1 percent of the oil and gas now being consumed as fuel throughout the «•orld'. But petroleum is not the . ~ <. only nutrient that can be used. The organisms can be successfully nourished with carbohydrates that might~~ otherwise be discarded as waste-corncobs, sugar-beet << ' residues, citrus pulp, molasses, and so forth. A Srredish : scientist, Carl-Goran Heden of the Karolinska Institute;`1 has proposed-that huge floating fermentation~factories be 4 ~ built to exploit the abundant sources of vegetable matter along the shores-of tropical and subtropicali lands. 4 . -With soyTbeans plentiful until recently, there was little;_~ ~ incentive for U.S. companies to work on single-cell pro- .:~ tein, although some oil producers, notably American Oil, are carrying on research in the field! Elsewhere in the world, though„interesthasbeen running strong. Fermen- tation plants making singlie-cell protein are already operating in quite a few countries. And scientists from the underdeveloped world are beating a ath to such U.S. companies as Fermenta ion esign, Inc., of Bethleheni ;Br Pennsyh-ania, a ivision of NeN Co. Fermentation esign is Nvorkin with Mexican and In ian scien ists, among o ers, and is about to deliver an automa pr o p ant for ro ti n of single-cell protem o e oti iet Union. Dependent mankind Underdeveloped countries are interested in single-cell protein as human food because eventuallyy it could be pro- duced' cheaply compared to meat. There appear to be no basic toxicity problems, even when petroleum is the nutrient. Properly purified, the protein presents no serious health hazards-at least none have been discov- " ered-and has no taste or smell of petroleum. There are problems of acceptability for humans, and that's where genetic manipulation of the microorganisms is expected to help. For one thing, the relatively thick cell walls of yeast sometimes make the stuff difficult to digest. Research~ to develop improved strains of yeasts is under way in~ both France and the U.S. Objectives : thin- ner cell walls, lower content of certain chemicals that could aggravate such conditions as gout, and larger yeast cells for easier harvesting. In various ways, then, people are going to be making more and more use of microbes as time goes by. Without realizing it, man has depended on microbes all along, of course. In performing their functions in nature, most notably in the recycling of basic nutrients, microor- ganisms are and have been essential' to human survival. It appears that in years ahead they will become even more so. E:CD