BIOTECHNOLOGY RESEARCH AND AGRICULTURAL STABILITY

Jack Doyle

T.72 f o l l o w i n g a r t i c l e has been r e p r i n t e d w i t h permiss ion o f t h e National Academy o f S c i e n c e s . I t f i r s t appeared i n I s s u e s i n Sc i ence and Technology Fa l l 1985, volume 11, number 1 , ( p u b l i s h e d b y t h e National Academy o f S c i e n c e s , t h e Nat ional Academy o f Engineer ing , and t h e I n s t i t u t e o f Medic ine) where i t was one o f f i v e a r t i c l e s on t h e t o p i c o f " A g r i c u l t u r e i n T rans i t i on . " The f u l l i s s u e ($6.00) can b e ordered from t h e NAS P u b l i c a t i o n s Department, 2101 C o n s t i t u t i o n Avenue NW, Washington, D. C. 20418.

A few years ago a t the Smithsonian I n s t i t u t i o n ' s National Museum of American History, an exhibition en t i t l ed "The Changing American Farm: 1831-1981" celebrated the one-hundred-f i f t i e t h anniversary of Cyrus McCormickls invention of the reaper, and more broadly, America's vaunted agricul tural pro- duc t iv i ty . Various displays recounted the h i s t - or ical progression of mostly mechanical techno- logy tha t has made the U.S. farmer the envy of the world: McCormickl s reaper, John Deere's s teel plow of 1837, Benjami n Hol t ' s horse-drawn combi ne of the 18801s, Henry Ford's t r a c t o r of 1917, the sel f-propel1 ed combine of 1938, the spindle cotton picker of 1943, and International Harvester 's Axial-Flow combine of 1977.

This technology has helped make the United States a world leader in food production. In 1800, fo r example, i t took 373 manhours t o produce 100 bushels of wheat. Today i t takes l e s s than nine manhours to produce the same quantity. In 1900, one U.S . farmer suppl ied seven other people with food, f i b e r , and other agricul tural products, Today the average U.S. farmer supplies more than 75 people.

Of course, t h i s impressive productivity i s not the r e su l t of mechanical invention alone, b u t a1 so of s c i e n t i f i c advances in plant breeding, l ivestock genet ics , f e r t i l i z e r and pest ic ide use, i r r i ga t ion technology, and improved farm manage- ment practices generally.

Because of the interplay of genet ics , f e r t i l i z - e r s , and pest ic ides , f o r example, corn yields have increased about a bushel per acre every year since 1930--from an average yield then of 40 bushels per acre to more than 100 bushels per acre today. Similar productivity gains have been made in 1 ivestock. A 1 though the U.S. dairy herd has been cut in half since 1950, i t produces the same to ta l amount of milk on one-third l e s s

feed. In a1 1 areas of plant and animal agr i - cu l ture , "science power" has been the driving force behind steadi 1 y increasing yields . Our modern agricul tural system and methods a re now exported and propounded worldwide.

A VULNERABLE SYSTEM

Modern agricul tu re , however, i s high-pedigree agr icu l ture ; i t i s a pampered system tha t i s tended and maintained by techno1 ogy and driven to perform a t peak leve ls . In t ha t sense our agricul tural system might be compared to a thoroughbred race horse. I t i s a system b u i l t increasingly on hybrid crops and 1 ivestock, heavy inputs of f e r t i l i z e r , an t ib io t i c s , water, and pest ic ides , a system tha t i s c a p i t a l , energy, and technology intensive. I t i s , in shor t , a demanding, high-strung system.

As such, i t has i t s dependencies, i t s s ide e f f ec t s , and i t s vul nerabi 1 i t i e s . Because many of the inputs t ha t sustain modern agr i - cul ture are petrol eum-based and mechanical 1 y administered, agr icu l ture has become energy dependent--with the high costs and insecur i t ies such dependency e n t a i l s . Despite dramatic hikes in nitrogen prices since the 1970s, heavy use of nitrogen f e r t i l i z e r continues, with attendant problems of runoff and groundwater contamination. Nitrates and n i t r i t e s from fer - t i 1 i ze r runoff have i n f i l t r a t e d some drinking water supplies, posing a health t h r e a t , especi- a l l y t o young children. Pest ic ides , too, a re increasingly suspected as carcinogens and mutagens, in addition to t h e i r well-known dele- ter ious e f f ec t s on beneficial insects and wild- 1 i f e . Moreover, despi te our heavy use of pest- icides and herbicides, nearly 40 percent of U.S. crops a re s t i l l l o s t t o diseases and pests -13 percent t o insec ts , 12 percent t o plant

1 3

pathogens, and 12 percent to competing weeds. combat agr icu l tu ra l pes t s . Genet ical ly im- proved herds of da i ry cows and beef c a t t l e , a s

Monocultures of hybrid corn and Holstein cows we1 1 as. hogs ,poul t r y , and sheep, may produce have been and continue t o be highly vulnerable t o more O n l e s s feed. Work i s a l s o under way on disease and pes t i l ence . The ex ten t of these vul- crops t h a t a r e more t o l e r an t of hea t , co ld , n e r a b i l i t i e s has been p a r t l y masked by surplus drought, f looding, and s a l t y s o i l s , and on crop s tocks , crop subs t i t u t i ons , and, in some cases , p lan t s t h a t a r e r e s i s t a n t t o herbic ides and sheer luck. Nonetheless, the 1 i s t of actual pes t i c ides o r t h a t have improved response t o epidemics and near ca lami t ies in the past 15 f e r t i l i z e r . Some biotechnologis ts promise a years i s subs tan t ia l : the southern corn l e a f - new genet ic d i v e r s i t y throughout plant and b l igh t of 1970-71, c i t r u s canker i n f e s t a t i on in animal ag r i cu l t u r e , lower cos t s and higher Flor ida , avian influenza in the mid-Atlantic p r o f i t s f o r farmers, and b e t t e r crops and l ive - poul t r y s t a t e s , and the Mediterranean f r u i t f l y , stock breeds f o r t he t h i r d world. among o thers . In add i t ion , the per iodic ravages of drought and f r o s t can humble even the strong- Indeed, the promises being made in the name of e s t p lan t va r i e t y . Frost damage a lone causes biotechnology a r e subs t an t i a l , even though the some $1 b i l l ion in losses annual'ly in the United science underlying these app l ica t ions i s s t i l l S t a t e s , and $14 b i l l i o n worldwide, uncer ta in . Generally, we know l e s s about

plants than we do about animals, in Genet ic is t William L . Brown, former par t because federal support f o r chairman of the board of Pioneer Hi- cancer research has focused a t t en t i on Bred Internat ional and now chairman of /lkeathoroughbred on animal c e l l biology. Few genes in the National Academy of Sciences ' race horse, modern the p lan t realm have even been charac- Board on Agricul ture , has noted t h a t agriculture is a t e r i z ed . And when i t comes t o actual !hen our agr icul tu ra l system i s r u n n - demanding, high- genet ic engineering, s c i e n t i s t s a r e ing r i g h t , i t s performance i s simply strung system, only beginning t o discover how t o mani- dazzling--"but watch out when some- nourished by pula te single-gene t r a i t s , l e t alone thing goes wrong." In 1983 something technologyanddriven funct ions such as nitrogen f i x a t i o n , d i d go wrong for corn farmers in the toperformatpeak be1 ieved to be governed by 30 or more Midwest: drought. "Many farmers in- levels. genes. curred 1 arge economic 1 osses ," Brown explained, "because t h e i r investment B u t assuming t h a t the s c i e n t i f i c in inputs t o support a 150-bushel (per ba r r i e r s wi l l be overcome--and advances ac re ) crop withered along with t h e i r corn have been coming more rap id ly than anyone ever p lan t s . " Brown and others have begun t o r a i s e thought they would even f i v e years ago--the key concerns about the v o l a t i l i t y of our high-tech, question about agr icul t u r a l biotechnol ogy i s , high-yield system. "As we o f f e r t he farmer in- How wil l i t be used? Will i t simply add newer creasingly sophis t icated and cos t l y technologi- increments of pedigree improvement t o the high- cal packages, we inadver tent ly exacerbate two tech , high-yield system t h a t i s a l ready in re la ted sources of i n s t ab i l i t y in ag r i cu l t u r e . place--exacerbating i t s vu lne r ab i l i t y , i t s s ide High-yield production systems a r e of ten more e f f e c t s , and i t s v o l a t i l i t y ? Or will i t reduce v o l a t i l e in terms of harvested production, and production cos t s f o r farmers, broaden the more e r r a t i ? in terms of p r o f i t f o r the farmer," genet ic and economic base of ag r i cu l t u r e , and Brown says. In o ther words, t he thoroughbred reduce negative environmental and public heal th runs well only when everything c l i c k s . s i de e f f e c t s ?

Into t h i s agr icu l tu ra l system, with a l l i t s s t reng ths , complexit ies, and vul nerabil i t i e s - - both biological and pol i t i c a l --comes biotechnol- ogy. We a r e now poised on the threshold of a new era of agr icu l tu ra l science and technology tha t may bo l s t e r , f o r t i f y , and eventual ly super- sede the t r ad i t i ona l techniques of plant and animal breeding, make obsolete t h e brute-force use of ag r i cu l t u r a l chemicals, and increase product ivi ty beyond anything ever dreamed o f .

Recombinant D N A and t i s s u e cu l t u r e techniques may o f f e r new ways t o enhance the nu t r i t i ona l content of food and forage crops and t o develop crops r e s i s t a n t t o insec t s and disease . Engin- eered biological pes t i c ides may a l so be used t o

With t h i s new technology we a r e a t a crossroads, and the path we choose may a f f e c t not only the United S ta tes b u t much of world ag r i cu l t u r e . Our decisions on research d i rec t ion and invest - ment must be made ca r e fu l l y f o r i f commitments; of scarce t a l e n t and cap i t a l a r e made i n one d i r ec t i on , we may foreclose o ther opt ions . Commerce and entrepreneuria l genius have been a dr iving fo rce in ag r i cu l t u r a l innovation and r i s i ng product ivi ty i n the pas t . The fu ture d i rec t ion of agr icu l tu ra l biotechnology, however, should not be l e f t t o the market alone. Thoughtful public po l i c i e s a re necessary t o ensure t h a t promising options a re pursued-- including those t h a t a re f inanc ia l 1 y r i sky , longer term, and perhaps not a s commercially

4 DNA struclure

DNA can be described as "a w i n d i n g l a d d e r . "

l u c r a t i v e . We need t o examine which h i s t o r i c a l l y negl ec ted areas o f a g r i c u l t u r a l research may p r o f i t f rom gene t i c engineer ing, where scarce research d o l l a r s should be p u t f i r s t , t h e research r o l e o f t h e U.S. Department o f A g r i c u l - t u r e (USDA) and l a n d g r a n t and p r i v a t e u n i v e r s i - t i e s , and what new i n c e n t i v e s m igh t be c rea ted t o encourage i n d u s t r y t o pursue products i t migh t o therwise neg lec t . As a s t a r t i n t h a t process, i t w i l l be he1 p f u l t o examine what b io techno logy may o r may n o t do i n terms of i n c r e a s i n g t h e e f f i c i e n c y o f a g r i c u l - t u r a l p roduc t i on (and here I mean more empha- s i s on p r o d u c t i v i t y and l e s s on gross ou tpu t per ac re ) , reduc ing farmers ' cos ts , reduc ing a g r i - chemical use, broadening g e n e t i c d i v e r s i t y , and i nc reas ing economic s t a b i l i t y i n a g r i c u l t u r a l p roduc t i on and w o r l d markets.

YIELD HAS BEEN THE GOAL

I n t h e nex t 30 years w o r l d food p roduc t i on w i l l have t o double, i t i s est imated, t o meet demand. Th is cha l lenge cannot be met w i t h o u t s u b s t a n t i a l improvements i n a g r i c u l t u r a l y i e l d s . Y i e l d i s what farmers buy and what po l i t i c a l l eade rs w i t h masses o f people t o feed hope most f o r t h e i r s c i e n t i s t s t o achieve, whether b y c l a s s i c a l breeding techniques, t i s s u e c u l t u r e methods, o r gene t i c eng ineer ing . When R a j i v Gandhi v i s i t e d t h e Un i ted Sta tes i n June 1985, i t was n o t t h e computer-based sc iences and r o b o t i c s t h a t im- pressed him the most, b u t r a t h e r what b io tech - no logy m igh t do t o he lp him feed h i s n a t i ~ n . ~ The semi-dwarf wheat and r i c e v a r i e t i e s i n t r o - duced d u r i n g t h e Green Rev01 u t i o n i n t h e 1960s and 1970s helped p r o v i d e I n d i a w i t h t h e a b i l i t y t o feed i t s e l f ; Gandhi sees even g r e a t e r possib- i l i t i e s ahead w i t h b io techno logy .

Today t h e r e i s t a l k o f 300-bushel per ac re co rn and sorghum, 200-bushel pe r ac re wheat and ba r ley , and 100-bushel pe r ac re soybeans-- double and t r i p l e c u r r e n t y i e l d s . Crop y i e l d , however, i s a composite o f many p l a n t processes rang ing from how s t rong a c r o p ' s s t a l k i s t o t h e mo lecu la r i n t r i c a c i e s o f photosynthes is . High y i e l d i s n o t s i m p l y t h e consequence o f one gene b u t o f t h e i : n tecac t i on o f many.

When breeders and b io techno l o g i s t s t a l k o f improv ing y i e l d , t h e y i n v a r i a b l y t a l k o f hy- b r i d i z a t i o n - - t h e process o f c ross ing two d i f f e r e n t p l a n t v a r i e t i e s o r animal breeds t o o b t a i n a g e n e t i c a l l y improved one. Corn and sorghum y i e l ds , f o r exampl e , have increased more than 300 percent s ince t h e y were hyb r id - i z e d i n t h e 1930s and 1940s. However, o t h e r major crops l i k e wheat and soybeans have been d i f f i c u l t t o h y b r i d i z e b y t r a d i t i o n a l tech- niques, and produc ing commercial q u a n t i t i e s o f h y b r i d seed from these crops i s c o s t l y and t ime -consuming . Now, however, b i otechnol ogy i s be ing used t o overcome some o f these d i f f i c u l - t i e s .

One company, P l a n t Genetics, I nc . o f Davis, C a l i f o r n i a , i s us ing a t i s s u e c u l t u r e technique known as somatic embryogenesis t o produce c lones o f a hand-pol 1 i nated c e l e r y h y b r i d . I n t h i s process t i n y p l a n t embryos a re generated from t h e h y b r i d c e l e r y t i s s u e and then "batched up" b y t h e thousands i n a fe rmen ta t i on process. These embryos, c a r r y i n g t h e d e s i r e d t r a i t s o f t he parent 1 ine , a re then encapsulated i n a polymer seed coat t o be s o l d as " s y n t h e t i c " h y b r i d seeds.

Ag r igene t i cs Corpora t i on o f Boulder , Colorado, has patented a b io techno logy process t h a t a l l o w s f o r t h e r a p i d development and commerial p roduc t i on o f h y b r i d seed w i t h o u t t h e t r a d i - t i o n a l l i m i t a t i o n s on t h e gene t i c makeup o f t h e parent l i n e s . Th i s process, accord ing t o t h e company, pe rm i t s one o r bo th o f t h e parent 1 i n e s t o be g e n e t i c a l 1 y complex (heterozygous) r a t h e r than i nb red f o r u n i f o r m i t y (homozygous), p o t e n t i a l l y reduc ing t h e t ime needed t o develop h y b r i d seed.

Biotechnology may a1 so he1 p improve c rop y i e l d by improving t h e e f f i c i e n c y o f c e r t a i n b i o l o g i - ca l processes i n p l a n t growth, such as photo- syn thes is . Most a g r i c u l t u r a l crops conve r t 1 ess than 1 percent o f t h e energy they absorb f rom t h e sun, and even a t i n y increase i n t h i s con- v e r s i o n process cou ld mean a s u b s t a n t i a l inc rease i n crop y i e l d . The fede ra l government and a few major co rpo ra t i ons - - i nc lud ing Dow Chemical, Monsanto, and E l i L i l l y - - h a v e been research ing t h e gene t i cs o f photosynthes is . S p e c i f i ca l . ly , t hey a r e examining t h e genet ics o f ch lo ro - p l a s t s , t h e s i t e o f photosynthes is w i t h i n t h e

5 c e l l . Even tua l l y , i t may be p o s s i b l e t o gene- supp l ies . I n 1983, f o r example, farmers spent t i c a l l y engineer these o rgane l l es t o improve $18 b i l l i o n f o r purchased feed, $7.4 b i l l i o n f o r t h e e f f i c i e n c y o f photosynthes is , a1 though f e r t i l i z e r , $4 b i l l i o n f o r p e s t i c i d e s , $4 b i l l i o n the re i s s t i l l a l ong way t o go on t h i s f r o n t . f o r seed, $9.8 b i l l i o n f o r fa rm machinery and

$15.8 b i l l i o n f o r f u e l , l u b r i c a n t s , and machinery Other companies a re concen t ra t i ng t h e i r e f f o r t s up-keep. f o r i nc reas ing y i e l d i n one o r more s p e c i f i c crops. DuPont, f o r example, has i n t e g r a t e d i t s The p r i c e s p a i d b y farmers f o r p roduc t i on i n p u t s chemical growth r e g u l a t o r research w i t h i t s have r i s e n p r e c i p i t o u s l y d u r i n g t h e l a s t 15 years p l a n t b reed ing and p l a n t b io techno logy research o r so. USDA's index f o r general p roduc t i on i n - i n an a t tempt t o achieve a 10 t o 15 percent pu ts shows a doub l i ng o f p r i c e s p a i d b y farmers y i e l d i nc rease i n soybeans, accord ing t o between 1973 and 1983. For example, t h e average G.D. H i l l o f t h e company's a g r i c u l t u r a l c o s t per farm o f seed and p l a n t s soared b y 164 chemicals d i v i s i o n . 4 percent between 1972 and 1977. Today a mid-

western co rn farmer spends on the average about $46 per ac re on f e r t i l i z e r , $17 p e r ac re on pes-

"YIELD" REDEFINED t i c i d e s , $17 pe r ac re f o r seed, and about $18 p e r ac re f o r f u e l . C a p i t a l investments can be sub-

A1 t e r n a t i v e l y , b io techno logy a1 so o f f e r s t h e s t a n t i a l , too. I r r i g a t i o n investments i n t h e p o s s i b i l i t y o f improving p r o d u c t i v i t y w i t h o u t Great P l a i n s r e g i o n were $103 pe r acre i n 1950, i nc reas ing y i e l d pe r se - - i n o t h e r words, i n - rose t o $201 per acre b y 1970, and exceeded $500 creas ing t h e e f f i c i e n c y o f p roduc t i on . For per ac re by 1979. Some farmers a re now spending example, some p l a n t s produce n a t u r a l molecules as much as $35,000 a year on he rb i c ides and t h a t repe l i n s e c t s . As Sam Dryden, p res iden t $50,000 a year t o power i r r i g a t i o n systems. o f Ag r igene t i cs, says, eng ineer ing R i s i n g c o s t s a r e p a r t o f t h e reason such t r a i t s i n t o a g r i c u l t u r a l crops. why many farmers a r e now i n economic "cou ld be severa l o rde rs o f magnitude t r o u b l e. more c o s t e f f e c t i v e than t r a d i t i o n a l chemical approaches t o formul a t i ng , Reversing the high- W i l l b i o techno logy change t h a t ? manufactur ing, and app ly ing b ioc ides . " ~ieldorientationof Because b io techno logy i s capable o f Th is approach, however, m igh t a1 so r e - U-S-agriculture, even t u r n i n g o u t c e r t a i n k inds of p l a n t duce y i e l d somewhat. "The added va lue with a powerful tool c lones i n t h e m i l 1 i ons o r producing i n t h i s case may be one o f c o s t r e - like biotechnology, 1 i v e s t o c k vaccines i n huge q u a n t i t i e s d u c t i o n [ e l i m i n a t i ng t h e need f o r i n - willbe difficult inded. f o r pennies, i t should, presumably, be s e c t i c i d e a p p l i c a t i o n ] , n o t o f i n - ab le t o d e l i v e r lower c o s t seed, feed, creased ha rves t index [ y i e l d ] , " ex- and p e s t i c i d e s . And i n s o f a r as t h e p l a i n s Dryden. " I n any case, we gene i s t h e c e n t r a l i n g r e d i e n t o f should be he1 ped i f we r e f i n e d ou r use a g r i c u l tu re- -de termi n i ng t o a 1 arge o f t h e word ' y i e l d ' t o mean r e t u r n on e x t e n t whether-, o r t o what degree, investment r a t h e r than as measure o f gross b i o - supplementary i n g r e d i e n t s such as f e r t i 1 i z e r , mass p e r acre."5 p e s t i c i d e s , o r water w i l l be needed--"bui ld ing

i n " t r a i t s t h a t make crops h a r d i e r and ab le t o That may be e a s i e r sa id than done, however. I n r e s i s t pes ts should presumably do away w i t h t h e t h e Un i ted States, as we1 1 as i n many o t h e r need f o r some expensive supplements and c a p i t a l coun t r i es , p l a n t breeding programs, farm manage- equipment. ment p r a c t i c e s , p r i c e support formulas, farm c r e d i t , and agr ibus iness product development a r e "Imagine a s t r a i n o f wheat t h a t grows w e l l i n t h e a1 1 p red i ca ted on h i g h - y i e l d a g r i c u l t u r e . Re- d r y lands o f western Kansas--wi t h o u t heavy irri- ve rs ing t h a t h i g h - y i e l d o r i e n t a t i o n , even w i t h gat ion," s a i d N icho las Reding, Monsanto's execu- a powerfu l t o o l l i k e b io techno logy , w i l l be t i v e v i ce -p res iden t , a t a January 1984 meet ing o f d i f f i c u l t indeed. Rather, b io techno logy i s more t h e Kansas Board o f A g r i c u l t u r e . " O r a corn l i k e l y t o be used t o make the thoroughbred r u n p l a n t t h a t f i x e s i t s own n i t rogen . O r soybean f a s t e r , o r produce more, than i t i s t o make i t p l a n t t h a t - have even h ighe r p r o t e i n , o r d o n ' t s t ronger and more durab le . need t o be processed be fo re animal consumption.

O r c a t t l e t h a t conver t p r o t e i n t o meat w i t h an e f f i c i e n c y we o n l y dream about today . . . These

HIGH COSTS OF US. AGRICULTURE new techno log ies , l i k e those o f t h e pas t , w i l l g i v e American farmers t h e edge they need t o r e -

Biotechnology, as noted above, may o f f e r new main t h e most p r o d u c t i v e i n t h e wor ld . " o p p o r t u n i t i e s t o reduce farmers ' costs--and those cos ts a re s u b s t a n t i a l . I n t h e aggregate U.S. farmers spend n e a r l y t w o - t h i r d s o f t h e i r continued on page 8

cash r e c e i p t s each year t o purchase farm

BIOTECHNOLOGY: The What k DNA?

DNA-deoxyribonucleic acid-is the genetic material found in all living organisms. The characteristics of every living organism can be traced to the code of its DNA. Recombinant DNA, [rDNA), is both the process of combining the DNA of different organisms and the product of this process.

What do g m s do? The genetic code is present in every cell of every

organism. Depending on the cell's particular function, the code tells the cell what to do, how to act, and when to do it. For example, the human body has a gene, or several genes, that tell cells when to grow. Normally, this gene is bnm until a person reaches their early twenties or late teens. Then, another gene tells the body to stop producing the chain of reactions that stimulate growth, and the gene turns 'ofP.

How do genes worKl Each gene produces an enzyme that contributes to a

chain reaction; ultimately, normal functioning of the body is the result of a series of chain reactions. Another way to imagine how genes work would be to think of genes working together to create a domino effect Generally, no one gene is responsible for a single action

What is cbnhg? Cloning occurs as a result of isolating the DNA

within certain, specific genes. DNA is isolated by us- ing 'restriction enzymes,' that separate segments of DNA from its longer strand. These segments are then transferred into bacteria. By this process, specific segments of DNA can be patched into the genetic code of other organisms.

Bacteria provides an especially hospitable habitat for cloning, because it is able to multiply rapidly. Since the piece of transferred DNA has been im- planted into the bacterium's permanent genetic code, it is reproduced exactly through every generation of bacteria. When the bacteria are grown in large enough batches, the products from the new gene can be harvested and purified.

Terms of the Trade What k ~~

People often use the terms biotechnology. genetic engineering, and recombinant DNA (rDNA) inter- changeably. Actually they describe different classifications of activities in biology. Biotechnology is the broadest category. It describes both old and new techniques of manipulating organisms for specific purposes. According to a 1984 Office of Technology Assessment Report, biotechnology includes any technique % a t uses living organisms (or parts of organisms) to make or modify products, to improve plants and animals, or to develop rnicrowganisms for specific uses."

What is somatlc p e therapy and how does R dllfer from germhe gene therapy?

The idea behind somatic therapy is to replace genes whose absence or defectiveness causes genetic diseases (like cystic fibrosis or Huntington's disease). Scientists first remove the genetic code from a type of virus called a retrovirus, which is compatible with bone marrow cells, and substitute genetic material from a healthy gene. The altered virus is injected into the bone marmw, where it multiplies and forms healthy pone marrow cells. The bone marrow is then able to produce blood cells with healthy genes, which in turn produce the enzymes necessary for a normal metabolic process. Although still in the experimental stages, somatic therapy has been tested with success in laboratory animals.

Most authorities believe that genetic changes mede in somatic therapy do not get passed on to generations via the sex-alled 'germw-cells.

The other, more controversial gene therapy would involve changing the genetic make up of the genes carried in germ cells. While germcell alterations could reduce inherited genetic diseases, in the far- reaching future it could have the potential to alter genes that determine the hair and eye color, sex, and intelligence of an offspring. Both scientists and ethicists debate the consequences of germal l therapy, questioning the morality of tampering with already healthy genes. 0

MULTINATIONAL MONITOR FEBRUARY 28,1986

Reprinted with permission.

Genetic Engineering: A Chronology

First gene cloned. U.S. guidelines for rDNA research outlined at the Asilomar Conference.

Genentech, Inc. is the first genetics firm founded for commercial purposes.

Somatostatin (human growth hormone) is the f i s t product.

In Diamond vs. Chakrabarty the US. Supreme Court rules that microorganisms can be patented under existing law.

Genentech is the first biotechnology firm to offer stock publicly. It sets a Wall Street record for the faster price increase per share.

Initial public offering by Cetus sets Wall Street record for the largest amount of money raised by an initial public offer- ing--$I25 million.

More than 80 new biotechnology firms had been formed by the end of the year.

Human insulin is the f i s t rDNA phar- maceutical product approved for use in the United States and the United Kingdom.

First plant gene expressed in a plant of a different species.

Judge John Sirica blocks the scheduled en- vironmental release of rDNA organism.

The Gene Merchants Unilemr, a company that already owns palm oil,

rubber, copra, cocoa and tea plantations in West and Central Africa, Colombia, the Solomon Islands and Malaysia, is using biotechnology to improve yields of the oil and coconut palms and has established a sub- sidiary to sell cloned palm oil seedlings throughout Asia.

Mitsubishi. one of Japan's largest companies, has taken a small equity position in Sungene Technologies Corp., a California-based biotechnology company, and may eventually help market and distribute some of Sungene's agricultural inventions in Asia.

Kemira OY, Finland's largest chemical concern. and owner of fertilizer terminals in Malaysia, Thailand and Guatemala, has a research contract with Calgene, Inc, to develop herbicide-resistant varieties of turnip rape.

Royal Dutch-Shell, the European energy giant, is developing hybrid wheat strains and is also studying the genetics of herbicide resistance in corn.

Nestle, the world's largest food corporation, has a research agreement with Calgene, Inc. to develop herbicide-tolerant varieties of soybeans.

Kirin Brewery of Japan has invested $1 million in the California-based Plant Genetics, Inc.. and will market that company's 'synthetic seed' technique and products throughout Asia and the Pacific Rim.

Upjohn, one of the world's largest veterinary sup- pliers, signed a 10-year agreement with the Minnesota-based Molecular Genetics, Inc. to distribute that company's genetically-made animal health prod- ucts in some 57 countries.

Hindustan Lever. an affiliate of Unilever, is work- ing on bio-insecticides in India.

Carnation, a subsidiary of Nestle that is already involved in Mexico, Peru and the Philippines with dairy and farm assistance programs, has also been ac- tive in the livestock engineering business, and has negotiated a number of embryo export deals with several African nations.

Rhone-Poulenc, a major French chemical con- cern, has a research contract with Calgene, Inc. to develop sunflower varieties resistant to the herbicide Bromoxiynil. 0

NEW DANGERS

A1 t e r n a t i v e l y, b i o t e c h n o l o g y may be app l i e d i n ways t h a t i n c r e a s e t h e need f o r chemica l and energy i n p u t s , t h e r e b y r a i s i n g t h e c o s t o f p r o - d u c t i o n . I f b i o t e c h n o l o g y i s s u c c e s s f u l i n b r i n g i n g more h i g h - y i e l d i n g h y b r i d s t o marke t , f o r example, t h a t w i l l no doub t mean i n c r e a s e d f e r t i l i z e r use. A f t e r t h e i n t r o d u c t i o n o f hy- b r i d c o r n v a r i e t i e s , t h e average f e r t i l i z e r use o f U.S. f a rme rs i n c r e a s e d t e n - f o l d . Between 1947 and 1973 t h e average f e r t i l i z e r a p p l i c a t i o n on U.S. c o r n l a n d i n c r e a s e d f rom abou t 20 pounds p e r a c r e t o more t h a n 200 pounds p e r ac re . S i m i l a r i n c reases i n f e r t i 1 i z e r (and p e s t i c i d e ) use c o u l d be expec ted w i t h t h e i n t r o d u c t i o n o f new h y b r i d wheat, c o t t o n , soybeans, and o t h e r c rops .

B i o t e c h n o l o g y may h e l p r educe p e s t i c i d e use i n a g r i c u l t u r e and may l e a d t o more s o p h i s t f c a t e d and p r e c i s e methods o f chemica l app l i c a t i o n . But , depending on t h e cou rse o f r e s e a r c h and c a p i t a l i n ves tmen t i n t h e n e x t few years , b i o - t echno logy may be a p p l i e d i n ways t h a t l e a d t o g r e a t e r chemica l use, e x a c e r b a t i n g e x i s t i n g en- v i ronmenta l prob lems and perhaps c r e a t i n g en- t i r e l y new ones.

B i o t echno logy may h e l p us r educe o u r dependence on chemica l p e s t i c i d e s i n two ways: ( 1 ) t h r o u g h t h e g e n e t i c e n g i n e e r i n g o f c r o p s t h a t a r e more b r o a d l y r e s i s t a n t t o o r even t o l e r a n t o f d i seases and i n s e c t s , and ( 2 ) t h rough t h e i n - formed and c a r e f u l use (and p o s s i b l e g e n e t i c enhancement) o f "good" m i c robes and i n s e c t s t h a t d i s p l a c e , r e p e l , o r k i 11 "bad" ones.

Fo r t h e most p a r t , when b i o t e c h n o l o - F i r s t c o n s i d e r c r o p b r e e d i n g f o r g i s t s , p l a n t b reeders , and a g r i c u l t- d i sease and i n s e c t r e s i s t a n c e . Today u r a l economis ts t a l k o f r e d u c i n g t h e i n t h e U n i t e d S t a t e s t h e r e a r e approx- f a r m e r ' s c o s t s , t h e y mean imp rov i ng Biotechnolog~maybe i m a t e l y 1 5 0 c r o p v a r i e t i e s r e s i s t a n t h i s y i e l d and h i s income p e r ac re , applied in ways that t o one o r more k i n d s o f d i sease , 150 t h e r e b y l o w e r i n g h i s c o s t s i n r e l a t i o n lead togreater v a r i e t i e s r e s i s t a n t t o nematodes, and t o h i s income. I n t h i s c o n t e x t c o s t s chemicaluse, ove r 100 v a r i e t i e s r e s i s t ? n t t o some can s t i l l r i s e as l o n g a s y i e l d does. exacerbatingexisting 25 t ypes o f i n s e c t p e s t s . 7 Imp ress i ve T h i s s c e n a r i o assumes, however, t h a t environmental as t h i s may sound, t h e r e a r e no c r o p t h e p r i c e f a rme rs w i l l g e t f o r a problemsandperhaps v a r i e t i e s r e s i s t a n t t o many d iseases bushe l o f c o r n o r wheat w i l l rema in creating new ones. and i n s e c t p e s t s . I n t h e m idwes te rn cons tan t . Bu t i f b i o t e c h n o l o g y r a i s e s Corn Be1 t, f o r example, t h e r e a r e a t y i e l d s t o o d r a m a t i c a l l y , i t c o u l d de- l e a s t 30 i n s e c t p e s t s and 50 d i s e a s e p ress ma rke t p r i c e s i n t h e aggrega te , pathogens t h a t can a t t a c k co rn . So a c t u a l 1 y e x a c e r b a t i n g t h e f a r m e r ' s c o s t - p r i c e f a r , c o r n v a r i e t i e s have been deve l oped t h a t squeeze. Some wouid argue, however, t h a t t h i s r e s i s t abou t 22 o f t h e most damaging c o r n s c e n a r i o changes i f one assumes t h a t t h e number d iseases . The r e c o r d f o r d e v e l o p i n g new i n s e c t o f f a rme rs w i l l be reduced as b i o t e c h n o l o g i c a l - r e s i s t a n t c o r n v a r i e t i e s , however, i s n o t as app l i c a t i o n s i n c r e a s e t h e o v e r a l l e f f i c i e n c y o f good. Corn i s one o f t h e n a t i o n ' s l a r g e s t use r s a g r i c u l t u r e . o f i n s e c t i c i d e s , accoun t i ng f o b a h e f t y 25 pe r -

c e n t o f t o t a l i n s e c t i c i d e use.

PESTICIDE DEPENDENCY-YES OR NO?

Nat ionwide , p e s t i c i d e s and h e r b i c i d e s a r e i n - c r e a s i n g l y be i ng f ound i n s u r f a c e and ground- wa te r s u p p l i e s . I n t h e p a s t two yea rs a lone , t h e Env i ronmenta l P r o t e c t i o n Agency ( EPA) has i n i t i a t e d r ev i ews on a t l e a s t h a l f a dozen wide- l y used a g r i c u l t u r a l p e s t i c i d e s t h a t a r e now suspected as ca rc inogens .

P u b l i c concern abou t t h e p o t e n t i a l t o x i c i t y o f t h e s e chemica ls a l s o appears t o be r i s i n g . I n a January 1984 consumer s u r v e y conduc ted b y t h e Food M a r k e t i n g I n s t i t u t e , 77 p e r c e n t o f t h o s e p o l l e d expressed concern o v e r p e s t i c i d e and h e r - b i c i d e r e s i d u e s i n food , i n d i c a t i n g t h e p rob lem t o be a " s e r i o u s hazard . " By c o n t r a s t , c h o l e s - t e r o l was judged t o be a s e r i o u s haza rd b y 45 pe r cen t , s a l t b y 37 p e r c e n t , a d d i t i v e s b y 32 pe r cen t , sugar b y 3 1 p e r c e n t , and a r t i f i c i a l c o l o r i nq b y 26 ~ e r c e n t o f t hose surveyed.

One p e s t , t h e wes te rn c o r n rootworm, has been expanding i t s range by 140 m i l e s a y e a r i n an ever-en1 a r g i ng c i r c l e t h a t began i n s o u t h e r n Nebraska i n 1960. It i s now f ound i n 18 s t a t e s . I n a d d i t i o n , some o f t h e chemica l i n s e c t i c i d e s used t o t r e a t t h i s p e s t a r e now showing up i n m idwes te rn groundwater s u p p l i e s . As o f 1984 no roo tworm- res i s t a n t c o r n v a r i e t i e s were a v a i l a b l e . One ma jo r o b s t a c l e i s t h a t no c o r n germplasm w i t h r e s i s t a n c e t o t h i s p e s t has been i d e n t i f i e d .

I n t h e sou theas te rn U n i t e d S ta tes , chemica l p e s t i c i d e s - - n o t r e s i s t a n t p l a n t v a r i e t i e s - - h a v e been t h e c h i e f means o f c o n t r o l l i n g soybean i n s e c t s , nematodes, and seve ra l p l a n t d i seases . I n Alabama, f o r example, t h e r o o t - k n o t nematode and t h e soybean c y s t nematode a r e p a r t i c u l a r l y vex i ng prob lems. Bo th had been a lmos t e n t i r e l y c o n t r o l l e d b y two nema t i c i des - -e thy l ene d i b r o - rnide (EDB) and d ib romoch lo ropropane (DBCP)--

unti l EPA banned them fo r public health reasons. That prohibition revealed how dependent soybean growers were on these pest ic ides , as well as how l i t t l e breeding has been undertaken to develop nematode-resistant soybean va r i e t i e s . In some breeding programs such work i s now under way.

Genetic engineering may make i t possible t o avoid some of the l imitat ions of conventional plant breeding for resis tance. I t could speed the process of germplasm screening and evalua- t ion f o r resis tance t r a i t s . And with the new- found a b i l i t y t o t ransfer genes from one spec- ies o r genus t o another, genetic engineers need no longer confine t h e i r search f o r resis tance genes to compatible species; some predict t ha t the en t i r e plant kingdom will become an open- ended gene pool . This means for example, tha t cer tain genetic t r a i t s of the oak tree--a species t ha t i s not bothered by the rus t s of wheat--could conceivably be moved in to commerc- ia l wheat va r i e t i e s t o make them permanently r e s i s t an t to ru s t . Some biotechnologists even ta l k boldly of making crops "immune" t o disease and insects . By contrast ,pl ant breeders a re more inclined to ta l k of " r e l a t i ve resistance" and "re1 a t i v e suscepti bi 1 i t y . I '

Howard Schneiderman, Monsanto's senior vice- president f o r research and development, predicts tha t some genetical 1 y engineered major crops r e s i s t an t t o insects and other pests will be on the market by the 1990s. . The r e s u l t , he adds, will be decreased dependence on pest ic ides . "We will have shif ted the central t h rus t of plant protection in some key areas from t r e a t - ment t o prevention. "9

ADAPTING RESISTANCE

This approach may not be without d i f f i c u l t i e s and s ide e f f ec t s , however. In the development of insec t and disease r e s i s t an t va r i e t i e s by conventional means, plant breeders have general 1 y employed a one-genelone-pathogen type of r e s i s - tance, sometimes cal led "gene-for-gene" breed- ing--a pract ice tha t may be followed in genetic engineering as well. Crop va r i e t i e s with s ingle- gene resis tance a re almost completely r e s i s t an t to the predominant s t r a i n of the pest--until an adaptation occurs. Jus t a s a pest can become immune t o a pest ic ide, so can i t overcome the resis tance produced by a s ing le plant gene.

, Si ngl e-gene resis tance more or 1 ess beckons adaptation by the pest and i t s mutation in to new s t r a ins , rendering the crop var ie ty , i f widely planted, susceptible t o devastation or epidemics.

corresponding increase in the frequency of virulence genes (genes tha t enable the pathogen t o overcome the p l an t ' s resis tance gene) in the pathogens tha t a t tack cer ta in crops.10 This has been'reported in Austral ia , fo r example, in breeding wheat for resis tance t o stem r u s t , barley fo r resis tance t o powdery mildew, tomato fo r resis tance t o leaf mold, and l e t t uce fo r resis tance t o downy mi 1 dew. Many pathogenic organisms have the a b i l i t y to t r ans fe r genes among themselves asexually, increasing the r a t e a t which they can develop virulence genes and thus adapt t o and overcome single disease re- s is tance genes in new crop v a r i e t i e s . l l This i s one reason why some new crop va r i e t i e s l a s t as 1 i t t l e as f i ve years before they a re overtaken by a new s t r a i n of pathogen.

"Intensive modern agricul tural methods accele- r a t e the evolution of new pest types, requiring plant gene t ic i s t s to more rapidly breed genes in to commerical cu l t i va r s from re s i s t an t re- 1 a t i ves , " says Cal gene, a biotechnol ogy company in Cal ifornia , in one of i t s recent brochures. The company holds out biotechnology a s a solut- ion: "bio-engineering wi 1 1 speed t h i s t ransfer process t o keep pace with the pathogens, expand the gene pool t o unrelated organisms, and even create synthet ic resis tance genes in the t e s t tube." B u t i f genetic engineering continues t o employ gene-for-gene plant breeding, might i t not simply speed and extend the pract ices of the past , thereby hastening the adaptation of new s t r a ins of disease and insec ts?

On t he other hand, biotechnology might help plant breeders t o impart a broader, multiple- gene type of disease and insec t res i s tance t o agricul tural crops, but t h a t will be more d i f f i - c u l t t o accomplish in the short run. Sc ien t i s t s a r e j u s t beginning t o learn of the interact ion pest and plant genes, and more basic know1 edge in t h i s area i s needed. And, as noted e a r l i e r , only single-gene t r a i t s have been successfully

There i s some evidence suggesting t h a t the use of Isingle-gene breeding may be contributing t o a

transferred to date. Transferring multiple-gene t r a i t s successfully and achieving coordinated expression--without affecting other plant func- tions--is a considerable challenge.

BlOLOGlCAL CONTROLS

The second way in which biotechnology could re- duce pesticide use i n agriculture i s through the development of biological control s . Consider, for exam~le. the bacterium Bacillus

much headway against conventional pesticides. The biologicals typical ly are appl icable to only one or a few target pests, are active only a t certain pest stages or seasons, and are n o t per- s i s t en t . They are usually destroyed by sun- l igh t , or are finicky about temperature, soi l conditions, and moisture. In addition, in the i r natural s t a t e they are not patentable. In short,potential payback from a commercial point of view has not been worth the e f fo r t , and most major companies have stayed away from them.

thuringiensis , known as BT. This bacterium, which k i l l s the insect larvae of the f lour moth, was discover- ed in the German province of T h u - r ingia in 1911. Since the 1940s BT has been widely used as a biological pesticide to ki 1 1 1 epidopterous insects (moth and but ter f ly) with toxic crystals formed in i t s spores.

On the other hand, biotechnology might help plant breeders impart a broader disease and pest resistance to crops, but that will be more difficult to accomplish in the short run.

Biotechnology i s rekindl ing some in- ' t e res t in t h i s area. One reason i s the 1980 U.S. Supreme Court decision in Diamond v . Chakrabary. I n t h a t case the Court ruled tha t i f microorganisms are a1 tered by man, they are no 1 onger a "product of nature" and are thus patentable. In addition t o Monsanto, other companies are working on fungi that attack weeds, bacteria that k i l l

I n l a t e 1984 a new twist emerged in BT's history as a biological pesticide. Monsanto announced tha t i t had spliced BT's toxin gene into another bacterium, Pseudomonas f l uorescens. P . f 1 uo- rescens inhabits the soi l of,mid- western corn f i e l d s , part icularly around corn plant roots. Monsanto i s planning to use P . fluorescens, appl ied as coating on corn seed, as a vehicle to carry BT's natural pesticide into the corn f ie lds to k i l l black cutworms, which are currently control led with synthetic pesticides.

B u t Monsanto's expressed optimism about t h i s technique may he clouded by the commercial l imitations of some biocontrol products, whether genetically engineered or not, and by potential problems with the i r safety and effectiveness. Recent studies suggest tha t even biologicals l ike BT can i c i t resistance in target insect populations." And E P A has announced i t s in- tention to regulate nonengineered (but nonindi- genous) microbial pesticides as well as gene- t i c a l l y al tered ones.

No genetical 1 y engineered biocontrol products (microbes, insects , or plants) have yet been marketed, b u t appl ications for f i e ld test ing are now pending before EPA and USDA. In f ac t , only a handful of nonengineered biological pesticides have been registered for use in the United States. A t l a s t count 13 microbial agents had been registered for use in about 75 separate biological pesticide products. Thi s compares t o some 1,400 chemical pesticide ingredients for- mulated into 35,000 or more registered products.

Traditionally, biological products have not made

vegetable worms, and viruses that make insects i l l .

One of the goals of biotechnologists now devel o p i n g genetical 1 y a1 tered bugs i s to make them more 1 i ke broad spec- trum chemical pesticides--i . e . , t o make them ki l l more than one specific pest and to make them more persistent .

Monsanto sc ient i s t s , for example, have expressed interest in transferring other toxin genes, in addition to BT's toxin gene, into i t s microbe designed to k i l l black cutworms, giving the mi- crobe the abi l i t y to ki l l other insects . I 3 Ecogen, a biotechnol ogy company formed specif i - call y to genetical 1 y engineer microbes, i s look- ing a t th i s possibi l i ty as well. "Cloning of two or more genes for d i s t inc t pesticide act- iv i ty in the same host cel l could generate a multipurpose pesticide, having a c t i v i t i e s against two or more very d i f ferent targets ( e -g . , two different insects , an insect and a weed, and an insect and a fungal disease) . The relat ive ease with which such different gene combinations can be potentially constructed by recombinant D N A technology makes the possi bi 1 i - t i e s virtual l y nl imi ted," says Ecogen sc ien t i s t Bruce Carl ton. 11

ECOLOGICAL NIGHTMARE

B u t by using biotechnology t o build "mu1 t ip le - warhead" microbes t h a t k i l l more than one species of pest, or those that l a s t longer in the environment, we may be creating bigger eco- logical problems than those we hope to replace. There has been 1 i t t l e sc ient i f ic study or data collection on how existing nonengineered

microorganisms behave i n na ture , l e t a lone any s o l i d understanding o f how g e n e t i c a l l y a l t e r e d ones m igh t behave. Some e c o l o g i s t s have r a i s e d concern t h a t g e n e t i c a l l y engineered microorgan- isms m igh t have unexpected consequences when re1 eased i n t o t h e environment. Any organism, engineered o r no t , can have d i s r u p t i v e e f f e c t s when i n t roduced i n t o a new ecosystem, t h e y c la im, c i t i n t h e Gypsy moth and t h e s t a r 1 i n g as examples.~5 G e n e t i c a l l y engineered m i c r o b i a l p e s t i c i d e s a l s o r a i s e o t h e r concerns. W i l l t h e t o x i n s k i l l b e n e f i c i a l i n s e c t s as w e l l ? W i l l t h e y p e r s i s t i n t h e environment? Molecu lar b i o l o g i s t s and e c o l o g i s t s a re j u s t beg inn ing a s c i e n t i f i c i a l ogue on some o f these quest ions. 1 g Many e c o l o g i s t s agree t h a t t h e r e i s l i t t l e s c i e n t i f i c i n f o r m a t i o n on which t o base p r e d i c - t i o n s about t h e behavior o f engineered organ- isms.17 L i t t l e i s known about t h e dynamics o f how organisms e s t a b l i s h themselves, o r why some species m u l t i p l y i n na tu re and o the rs do not , o r what a t t r i b u t e s make some organisms good a t d i s - seminat ion and o the rs poor. Some o f t h i s i n f o r - mat ion does e x i s t , b u t n o t always f o r t he organ- isms o f most i n t e r e s t t o gene t i c engineers.

WHAT HAPPENS TO AG-CHEMICALS?

Assuming f o r t h e moment t h a t g e n e t i c a l l y eng i - neered m i c r o b i a l p e s t i c i d e s and o t h e r b i o l o g - i c a l p roducts w i l l be safe and e f f e c t i v e , does t h e i r development mean t h a t chemical p e s t i c i d e s w i l l be phased o u t ? I n t h e l o n g run, maybe; i n t h e s h o r t run, p robab ly no t . I n f a c t , d u r i n g t h e nex t 10 t o 15 years, b io techno logy may 1 ead t o t h e des ign o f new, more s o p h i s t i c a t e d a g r i - c u l t u r a l chemicals and an i nc rease i n t h e use o f c e r t a i n p e s t i c i d e s .

S c i e n t i s t s a r e now i n v e s t i g a t i n g t h e gene t i c mechanisms i n c rops and i n s e c t s t h a t may enable them t o b e t t e r t o l e r a t e and r e s i s t t h e ill. e f f e c t s o f p e s t i c i d e s . A t l e a s t 20 companies are i nvo l ved i n t h e gene t i c eng ineer ing o f s t r a i n s o f corn, co t ton , and soybeans ab le t o r e s i s t he rb i c ides . (He rb i c ides a re sometimes l e t h a l t o t h e c rop as w e l l as t h e weed and some- t imes reduce c rop y i e l d s . ) I n many crops o n l y a s ingle-gene change i s necessary t o impar t her - b i c i d e res i s tance ; indeed, t h e r e l a t i v e s i m p l i - c i t y o f eng ineer ing h e r b i c i d e r e s i s t a n c e ex- p l a i n s i n p a r t t h e wide i n t e r e s t i n i t . Some h e r b i c i d e - r e s i s t a n t c rop v a r i e t i e s a re s l a t e d t o be on t h e market by 1989.

A r e p o r t i n Chemical Week noted t h e "s low b u t steady push" among h e r b i c i d e makers t o gene t i c - a l l y man ipu la te corn, soybeans, and o t h e r c rops t o increase t h e i r r e s i s t a n c e t o he rb i c ides . "The t h e o r y i s t h a t farmers would then be w i l l i n g

t o use even more o f t h e weed k i l l e r s sa fe i n knowledge t h a t t h e i r crops won ' t be damaged," accord ing t o t h e magazi ne.18 Some s c i e n t i s t s , however, say t h a t r e s i s t a n t c rop v a r i e t i e s a r e be ing designed t o work w i t h new, l e s s t o x i c he rb i c ides , and t h a t t h i s s t r a t e g y w i l l a c t - ua l 1 y reduce h e r b i c i d e use.19

Not much i s known about t h e lof ig-term env i ron- mental e f f e c t s o f he rb i c ides . A1 though general - l y n o t as t o x i c as t h e c h l o r i n a t e d hydrocarbon i n s e c t i c i d e s , h e r b i c i d e s can cause problems. A t raz ine , a l a c h l o r , and o t h e r h e r b i c i d e s t h a t were once thought t o d i s s i p a t e i n t h e s o i l have contaminated some w e l l s and have been found i n groundwater resources i n a t l e a s t 10 s ta tes . A few have r e c e n t l y been c i t e d f o r spec ia l r e - views b y EPA as suspected c a r ~ i n o ~ e n s . ~ o

J u s t as b io techno logy l i n k s he rb i c ides and c rop v a r i e t i e s i n new ways, i t i s a l s o l i k e l y t o ad- vance a new genera t ion o f chemical " p l a n t growth r e g u l a t o r s . " A few major chemical and pharmaceutical companies a re des ign ing and screening these chemical cousins o f p e s t i c i d e s and he rb i c ides . Such chemicals may one day be admin is te red t o vegetables and f i e l d crops as convent iona l p e s t i c i d e s now are, b u t t h e i r mis- s i o n w i l l be t o t u r n on o r o f f c e r t a i n p l a n t genes t h a t c o n t r o l f l o w e r i n g , growth, o r sene- scence. Th is "new chemistry," however, may not be much d i f f e r e n t from t h e " o l d chemis t ry " i n terms o f i t s environmental and pub1 i c h e a l t h impact. I n J u l y 1984 EPA announced a spec ia l rev iew o f Uni r o y a l ' s growth r e g u l a t o r A1 a r (daminozide) t o see i f i t poses a d i e t a r y cancer r i s k t o humans. E a r l i e r l a b o r a t o r y t e s t s i n d i - ca ted t h a t t h i s chemical causes tumors i n l a b - o r a t o r y animal s - 2 1 Sprayed on apples, A1 a r r e t a r d s r i p e n i n g i n t h e f i e l d , enab l i ng growers t o extend t h e ha rves t season and employ fewer p i c k e r s over a l onge r harves t . It a l s o makes

12 apples redder and increases t h e i r s h e l f l i f e b y two t o t h ree months.

I n sum, d e s p i t e some o f t h e more o p t i m i s t i c c la ims t h a t b io techno logy w i l l r e v o l u t i o n i z e pes t c o n t r o l and reduce chemical t o x i c i t y , i n ac tua l p r a c t i c e b io techno l ogy may do n e i t h e r . Ins tead, gene t i c and b i o l o g i c a l products may i n c r e a s i n g l y be made t o work toge the r i n t h e dominant p e s t i c i d e framework. However, if c a p i t a l and t a l e n t a r e i nves ted t o o h e a v i l y i n s t r a t e g i e s t o develop products such as h e r b i c i d e - r e s i s t a n t crops, o t h e r a1 t e r n a t i v e s , such as c ropp ing systems t h a t employ r o t a t i o n s o f a1 l e l o p a t h i c crops, might r e c e i v e l e s s a t t e n - t i o n .

THE DANGER OF MONOCULTURE

I n c e r t a i n reg ions o f t h e Un i ted Sta tes today, tens o f thousands o f acres of farmland a r e p lan ted i n cont inuous b locks o f t h e same v a r i e t - i e s o f corn, wheat, co t ton , and o t h e r crops. Although more than 250 v a r i e t i e s o f wheat a re a v a i l a b l e , f o r example, 10 v a r i e t i e s dominate t h e landscape, and s i x v a r i e t i e s accounted f o r n e a r l y 40 percent o f wheat acreage i n 1981. The s i t u a t i o n i s s i m i l a r i n o t h e r crops. Four v a r i e t i e s account f o r 65 pe rcen t o f t h e n a t i o n ' s r i c e acreage; s i x soybean v a r i e t i e s f o r 42 per - cent o f soybean land, and two pea v a r i e t i e s f o r 96 percent o f pea acreage.

The s i t u a t i o n i n l i v e s t o c k i s n o t much b e t t e r . The H o l s t e i n cow c o n s t i t u t e s about 70 percent of ( t h e n a t i o n ' s d a i r y herd. The White Leghorn and

i t s d e r i v a t i v e s p r o v i d e most o f t h e n a t i o n ' s eggs. Angus and Here ford c a t t l e account f o r more than 80 percent o f a1 1 r e g i s t e r e d breeds. Cross-breeding among e i g h t purebred hog l i n e s - -Berkshire, Chester White, Duroc, Hampshire, Landrace, Poland China, Spot, and Yorksh i re - - accounts f o r some 90 percen t o f U.S. ~ o r k pro- duc t i on .

Such gene t i c u n i f o r m i t y can c o n t r i b u t e t o d isease epidemics and widespread i n s e c t i n f e s t a - t i o n when res i s tance t r a i t s a r e overcome o r when s u s c e p t i b i l i t y e x i s t s th roughout a p l a n t o r l i v e s t o c k popu la t i on . I n t h e 1970-71 southern corn 1 ea f b l i g h t , f o r exampl e, t h e fungus Helminthosporium maydis was abe t ted by c o r n ' s manmade gene t i c u n i f o r m i t y : 80 percent o f t h e h y b r i d corn conta ined a m a l e - s t e r i l e cytoplasm t h a t was used f o r b reed ing purposes. The s i n g l e gene c o n f e r r i n g ma1 e s t e r i 1 i t y a1 so con fe r red suscept i b i 1 i t y t o t h e fungus, enabl i ng t h e patho- gen t o spread r a p i d l y from F l o r i d a t o Minnesota. More r e c e n t l y , t h e spread o f c i t r u s canker i n F l o r i d a seems t o have been abe t ted b y t h e u n i - f o r m i t y o f t h e s t a t e ' s c i t r u s v a r i e t i e s . About 90 percent o f t he s t a t e ' s orange harves t de- r i v e s from t h r e e v a r i e t i e s : Valencia, Ham1 i n , and Pineapple.

One way t h a t b io techno logy may h e l p t o reduce gene t i c vu l n e r a b i l i t y th roughout a g r i c u l t u r e i s through t h e development and domest ica t ion o f new crops and through e f f o r t s t o extend t h e p l a n t i n g range o f some e x i s t i n g spec ia l t y c rops . On1 y about 1 percent o f t h e 300,000 known species o f p l a n t s has been s t u d i e d f o r p o t e n t i a l use i n t h e product ion o f food, feed, f i b e r , and o t h e r sub- stances. Somewhere between 3,000 and 7,000 p l ant species have been used f o r food th roughout r e - corded h i s t o r y . O f these, r o u g h l y 150 have been c u l t i v a t e d t o t h e e x t e n t t h a t t h e y have entered w o r l d t rade. Most o f t h e w o r l d ' s human popula- t i o n i s f e d t o a l a r g e e x t e n t b y o n l y 15 p l a n t species. More a larming, perhaps, i s t h a t a mere th ree p l a n t species--corn, wheat, and r i ce - - con - s t i t u t e 75 percent o f t h e w o r l d ' s food supply.22

I f b io techno logy were successfu l im making j u s t a dozen p l a n t species commercial 1 y acceptabl e, a new measure o f b i o l o g i c a l and economic d i v e r s i t y would be gained. From a commercial s tandpo in t , however, t h e r e i s 1 i t t l e i n c e n t i v e t o b e g i n r e - search on such crops.

True, some energy companies are a1 ready s c o u t i n g f o r "energy crops" t o use f o r biomass p roduc t i on i f and when t h e o i l runs out , some chemical com- panies a re i n v e s t i g a t i n g p l a n t sources o f dyes and chemical substances, and pharmaceut ical co r - po ra t i ons a r e always l o o k i n g t o p l a n t s as sources of new drugs. Yet t o wnat e x t e n t have these i n d u s t r i e s o r government o f f i c i a l s r e a l l y thought about how such i n d u s t r i a l crops m igh t be

used as a t r a n s i t i o n c rop f o r some farmers? I f monocultures o f j o j o b a a r e s imp ly used t o r e - p lace monocul tures o f sorghum, how much b e t t e r o f f w i l l we be?

HYBRIDS: PRO AND CON

Bio techno logy may a1 so a s s i s t i n t h e development o f nonhybr id c rop v a r i e t i e s , b e n e f i t i n g farmers b y making a1 t e r n a t i v e (and perhaps more c o s t - e f f e c t i v e ) p roducts a v a i l a b l e . .Ever s ince t h e deve lo~men t o f h v b r i d co rn i n t h e 1930s. p l a n t ;~ ience- -e ;~ec ia l ly i n t h e appl i e d has been caught up i n t h e f e r v o r t o make crops hybr ids , and b io techno l ogy i s no except ion.

Hybr id seeds a re more va luab le than nonhybr id seeds because t h e f i r s t gen- e r a t i o n o f h y b r i d p l a n t s produces l a r g e r y i e l d s . Using t h a t seed t h e f o l l o w i n g year r e s u l t s i n l e s s " h y b r i d v i g o r " and lower y i e l d . Thus, t h e farm-

. e r must buy h y b r i d seed eve ry year . Hybr ids a l s o o f f e r another commercial advantage: o n l y t h e seed company knows t h e c o r r e c t parentage o f t h e h y b r i d l i n e , p r o v i d i n g what amounts t o a b u i l t - i n t r a d e sec re t . Because o f these commercial i n c e n t i v e s , few seed companies o r chemical f i r m s i n t h e seed business a r e l i k e l y t o conduct gene t i c research on open-po l l i na ted

i n 1982, " i s p a r t i c u l a r l y suscep t i b le t o changes i n i t i a t e d b y b io techno logy . " Trade p a t t e r n s between i n d u s t r i a l i z e d and developing c o u n t r i e s "may become p r o g r e s s i v e l y d i s l o c a t e d i f indus- t r i a l i z e d n a t i o n s sudde v become se l f - s u f f i c i - s l e n t i n c o l o n i a l crops. " P l a n t a t i o n - s t y l e sugar cane p r o d u c t i o n i n some p a r t s o f t h e deve lop ing wor ld, f o r example, cou ld be made obso le te i f i n d u s t r i a l i z e d n a t i o n s adopt cheaper, b io tech - no logy-ass is ted fe rmen ta t i on processes t o make sugar s u b s t i t u t e s , such as h i g h - f r u c t o s e syrup.

much o f I n a d d i t i o n , OECD sa id , because o f t h e "keenness realm-- o f i n d u s t r i a l i z e d c o u n t r i e s t o e x ~ o r t b i o t e c h - a1 1 no1 ogy

If biotechnology were successful in making just a dozen plant species commercially acceptable, a new measure of biological and economic diversity in agriculture would be gained.

co rn o r sorghum, and i n t h e near f u t u r e , on wheat o r soybeans. Open-pol 1 i nated v a r i e t i e s , however, m igh t reduce energy, p e s t i c i d e , and water requirements . Perhaps w i t h some c a r e f u l gene t i c eng ineer ing , open-pol 1 i n a t e d 1 i nes cou ld reach t h e y i e l d of some h y b r i d l i n e s , o r o f f e r a l i t t l e l e s s y i e l d b u t b e t t e r r e s i s t a n c e t o d isease and i n s e c t s than e x i s t i n g h y b r i d l i n e s . I n o t h e r words, b io techno logy i n t h i s a p p l i c a t i o n might reduce some o f t h e thoroughbred performance i n crops b u t s imu l taneous ly make them l e s s dependent on i n p u t s .

STORM-WARNING IN WORLD TRADE

The i n t r o d u c t i o n o f g e n e t i c a l l y made crop and 1 i v e s t o c k products may s w i f t 1 y and dramat ica l 1 y t rans fo rm t r a d i t i o n a l cen te rs o f a g r i c u l t u r a l p roduct ion , bo th w i t h i n and among na t i ons . Such changes cou ld d i s r u p t o r comp le te l y a l t e r t r a d - i n g p a t t e r n s and convulse w o r l d markets, w i t h r a m i f i c a t i o n s f o r bo th U.S. s g r i c u l t u r e and i n - t e r n a t i o n a l t r ade .

"Trade i n a g r i c u l t u r e , " s a i d t h e Organ iza t i on f o r Economic Cooperat ion and Development (OECD)

t o t h e T h i r d World," o the r ' t r a d i n g p a t - t e r n s cou ld change "w i thou t e i t h e r t r a d i n g p a r t n e r be ing f u l l y appr ised o f t h e r e s u l t . " A t a t ime when t h e Reagan a d m i n i s t r a t i o n i s i n c r e a s i n g i t s em- phas is on e x p o r t markets (as a means o f s h i f t i n g a g r i c u l t u r e t o a more " f r e e market" f o o t i n g ) , advances i n b i o t e c h - no logy cou ld make producer na t i ons o u t o f c o u n t r i e s t h a t have been valued U.S. customers. Through t h e i n t r o d u c t i o n o f improved wheat and r i c e v a r i e t i e s i n t h e 1960s and 1970s, I n d i a was t r a n s - formed from a g r a i n - i m p o r t i n g coun t r y t o a s e l f - s u f f i c i e n t one; w i t h b io tech - nology, t h i s p a t t e r n may be repeated i n many p a r t s o f t h e wor ld .

If s c i e n t i s t s , f o r example, a re suc- c e s s f u l i n g e n e t i c a l l y eng ineer ing

crops f o r increased c o l d to le rance , huge new mar- ke ts f o r c rop seed and suppor t i ng m a t e r i a l s cou ld be c reated. Across m i l l i o n s o f acres i n China and Russia, crops a re produced o n l y one o r two years o u t o f f o u r because o f t h e co ld . ( I n t h e Un i ted Sta tes as w e l l , t h e no r the rn range o f c e r t a i n crops cou ld be extended th rough improved c o l d t o l e r a n t . ) "Think o f Russia g e t t i n g wheat t o t o l e r a t e f reez ing , " says Ray Va len t i ne o f Calgene. "It would change t h e g e o - p o l i t i c s o f t h e wor ld . Indeed, t h e repercuss ions on g r a i n - e x p o r t i n g c o u n t r i e s 1 i ice t h e hi t e d States, Aus- t r a l i a , and Canada cou ld be phenomenal.

The Sov ie t s a r e a l r e a d y pu rsu ing b io techno logy i n hopes o f reduc ing t h e i r dependency on g r a i n i m - p o r t s . According t o E.F. h u t t o n a n a l y s t Z s o l t Harsanyi , t h e Sov ie t Union i s p u t t i n g tremendous e f f o r t i n t o producing s i ng l e - c e l l p r o t e i n - - t h a t i s , t h e use o f s i n g l e - c e l l microorganisms t o make p r o t e i n i n a fe rmen ta t i on process. By 1990, he says, t h e Sov ie t s cou ld be s e l f - s u f f i c i e n t i n animal feed.

Even t h e i n t r o d u c t i o n o f t i n y , g e n e t i c a l l y en- hanced microbes i n c e r t a i n 1 ow-product iv i t y reg ions cou ld have enormous t r a d e consequences. Much o f t h e s o i l i n t h e Southern Hemisphere, f o r example, s u f f e r s from aluminum t o x i c i t y t h a t

l i m i t s phosphate uptake. B io techno logy may companies have been acqu i red by chemical, phar- produce p l a n t s o r m i c r o b i a l i n o c u l a n t s t h a t maceut ica l , energy, agr ibus iness , and o t h e r cor - would enable crops t o more e f f e c t i v e l y scavenge po ra t i ons . Th i s t r e n d i s d r i v e n i n p a r t by the phosphate i n h igh aluminum s o i l s , accord ing t o d e s i r e o f ma jor c o r p o r a t i o n s w i t h i n t e r e s t i n Ralph Hardy, p r e s i d e n t o f B io techn ica I n t e r - b io techno logy t o ga in access t o t h e seed indus- n a t i o n a l . Such a development "cou ld make South t r y ' s market ing reach and p l a n t b reed ing exper- America an even more s i g n i f i c a n t t i s e . I n t h e Un i ted Sta tes alone, producer o f g r a i n s and thereby a Government has a more than 130 seed companies, hor- more fo rmidab le compe t i t o r w i t h U.S. responsibility to t i c u l t u r a l suppl i e r s , and seed c rop a g r i c u l t u r e . I' And accord ing conduct research on accessory businesses have been ac- t o Hardy, l i v e s t o c k b io techno logy those orphan q u i r e d b y co rpo ra t i ons . may a l s o decrease animal diseases products of

and thus enable A f r i c a t o develop a biotechnology for Some seed companies have been bought s i g n i f i c a n t meat-packing i ndus t r y .24 which no commercial and s o l d by major co rpo ra t i ons two

incentives exist. and t h r e e t imes. Many opera te as

I n q u i t e another ve in , however, b io techno logy cou ld enhance t h e p o s i t i o n o f t h e developed w o r l d as food producer t o t h e de t r imen t o f deve lop ing na t i ons . "The success o f our program i n enhancing t h e e f f i c i e n c y o f food p roduc t i on key t o t h e economies o f t h e developed w o r l d i s v e r y 1 i k e l y t o cause major d i s r u p t i o n s i n wor ld a g r i c u l t u r a l markets ,Ii says Nobel l a u r e a t e Joshua Lederberg. He adds t h a t we should be t h i n k i n g about these d i s r u p t i o n s "much more u r - gent1 y than we a re today. " Otherwise, "we may d i scove r t h a t we have t h e technology, we have the land, (and) t h a t we can produce a1 1 t h e w o r l d ' s food--and nobody e l s e can a f f o r d t o do i t because t h e y c a n ' t compete w i t h us. "25

FOOD POWER IN FEWER HANDS

The i n t r o d u c t i o n o f b io techno logy products cou ld a l s o have s i g n i f i c a n t economic consequences i n t h e Un i ted Sta tes , as Robert K a l t e r p o i n t s ou t [ i n Issues, f a l l 1985 - see "Res- ources" p. 221. The widespread adopt- i o n o f somatotropin, bov ine growth hormone, cou ld i nc rease mi 1 k p ro- d u c t i o n by an es t imated 30 percent . Th is might r e s u l t i n a 25 t o 30 percent decrease i n t h e number o f d a i r y farms and d a i r y cows. Those d a i r y farms t h a t remained cou ld ex- pect up t o a 26 percent increase i n farm r e t u r n s . A s i m i l a r p a t t e r n i s 1 i k e l y t o ensue i n o t h e r 1 i v e s t o c k sec tors . Ove ra l l , b io techno l ogy seems c e r t a i n t o d r a m a t i c a l l y a f f e c t t he economics o f farming, a c c e l e r a t - i n g t h e pace o f farm c o n s o l i d a t i o n and farm en1 argement . I n c e r t a i n farm supp ly i n d u s t r i e s - - most n o t a b l y t h e Nor th American and European seed i n d u s t r i e s - - t h e r e has been a dramat ic s h i f t i n ownership of seed businesses s ince t h e mid- 1970s. Hundreds o f sma l l e r seed

s u b s i d i a r i e s o r seed d i v i s i o n s o f t he ' parent cor - po ra t i on . Name changes, s h i f t s i n research, and reo rgan iza t i ons a re common. Other companies, once acquired, a r e then s o l d aga in i n p a r t s : fo rage seed t o one b idde r , soybean seed t o a another, wheat seed. t o y e t another. On a l e s s pronounced scale, a s i m i l a r p a t t e r n o f consol i- d a t i o n and co rpo ra te ownership has occur red i n t h e l i v e s t o c k gene t i cs area. I n years ahead b i o - technology i s l i k e l y t o f o s t e r p roduct unce r ta in - t y and i n s t a b i l i t y i n t he agr ichemica l , farm equipment, and f e r t i l i z e r i n d u s t r i e s as w e l l .

Desp i te t h e i n d i c a t i o n s t h a t a g r i c u l t u r a l b i o - technology may have enormous economic and p o l i t - i c a l e f f e c t s , bo th d o m e s t i c a l l y and i n t e r n a t i o - n a l l y , few governments o r co rpo ra t i ons are p lann ing f o r them. Unless f o r e s i g h t and p lann ing

a re brought t o bear on t h e f u t u r e use o f a g r i c u l t u r a l b io techno logy , c a p i t a l resources may be wasted, and s t r u c t u r a l i n s t a b i l i t i e s exacerbated w i t h farmers and consumers through- o u t t h e wor ld pay ing t h e s teepest p r i c e .

MAXIMIZING DIVERSITY

Today we can c l e a r l y see t h e cos ts and r i s k s assoc ia ted w i t h modern h i g h - y i e l d a g r i c u l t u r a l systems: h i g h energy costs, p e s t i c i d e t o x i - c i t y , i nc reas ing r a t e s o f p e s t r e - s is tance, f e r t i l i z e r r u n o f f , gene t i c u n i f o r m i t y , o v e r s p e c i a l i z a t i o n , and market vo l a t i 1 i ty'. We know, however t h a t b iotechnology--as we1 1 as con- ven t i ona l a g r i c u l t u r a l research--may h e l p us reduce o r e l i m i n a t e some of these cos ts and r i s k s . We would do w e l l t o app l y t h e bes t o f these techno log ies t o ou r most p ress ing problems. With b io techno l ogy, how- ever, we must move c a u t i o u s l y t o avo id c r e a t i n g new r i s k s o f perhaps a more d i f f i c u l t o rde r .

Biotechnology o f f e r s o p p o r t u n i t i e s t o advance b i o l o g i c a l a l t e r n a t i v e s and prov ide new farm management p r a c t i c e s t h a t may b e n e f i t t h i s n a t i o n and others, both i n terms o f p r o d u c t i v i t y and environmental p ro tec t ion . There a re obvious i n - t e r r e l a t i onsh ips between reducing a fa rmer ' s costs, reducing t h e use o f energy, pes t i c ides , and i r r i g a t i o n , reducing demands on scarce natu- r a l resources, and reducing the "ex terna l i t i e s 1 ' - t he o f f - s i t e publ i c h e a l t h and environmental costs - o f a g r i c u l t u r e . S p l i c i n g i n o r " t u r n i n g on" t h e r i g h t gene o r genes i n a p a r t i c u l a r crop v a r i e t y o r l i v e s t o c k breed may produce huge sav- ings w h i l e r a i s i n g p r o d u c t i v i t y . Fur ther , by r e - ducing genet ic u n i f o r m i t y we reduce t h e p o t e n t i a l cos ts o f emergency response, cumbersome and i n - e f fec t i ve quarant ine e f f o r t s , and business l o s s compensation. By i n t r o d u c i n g more gene t i c d i v e r - s i t y and more "new crop" v a r i e t y i n t o a g r i c u l - t u r e , we c rea te economic oppor tun i t y .

Yet i n t h e commercial sphere, as w e l l as i n t h e ha1 1s o f academe, t h e r e i s a tendency t o t h i n k o n l y o f "adding on" t o what a l ready e x i s t s . How many companies and u n i v e r s i t i e s pursuing he rb i - c ide - res i stance genes, f o r example, a r e spending t h e same amount o f money on making a l l e l o p a t h i c crops t h a t would repe l weeds w i t h t h e i r own chemicals, o r a r e seeking t o d iscover and/or develop n a t u r a l l y occur i ng m i c r o b i a1 herb ic ides t h a t might rep1 ace chemical he rb i c ides? How much i s USDA do ing i n such areas?

Government 1 eadership and research w i 11 be necessary, s ince few commerical i n c e n t i v e s now e x i s t f o r advancing such products o r farming p rac t i ces . USDA, t h e land g ran t u n i v e r s i t i e s , and publ i c-sec to r research i n s t i t u t e s have a r e - sponsi b i 1 i t y t o conduct research on those "orphan" products f o r which no commerical i n - c e n t i ves e x i s t . The federa l government should encourage farmers t o experiment w i t h such cropp- i n g a l t e r n a t i v e s , perhaps on set -as ide lands. Funding f o r such orphan products must be focused and appropr ia ted a t meaningful l e v e l s .

The advance o f molecular b io logy w i 11 b r i n g a w i n d f a l l o f knowledge t o b io logy. It may a l s o b r i n g a new "smartness1' t o a g r i c u l tu re- -a c l e a r e r understanding o f genes and gene expression, and thus a b e t t e r understanding o f t h e b i o l o g i c a l realm and how t o operate farms more s k i l l f u l l y , and perhaps more susta inab ly , i n t h e years ahead. Yet t h a t k i n d o f i n t e l l i g e n c e i s n o t p a r t o f t h e general a g r i c u l t u r a l l e x i c o n now, nor does i t appear t o be on the ho r i zon given ou r o r i e n t a t i o n t o thoroughbred a g r i c u l t u r e .

A t t h i s j u n c t u r e t h e w ises t course i s t o l o o k c a r e f u l l y a t a l l t h e a l t e r n a t i v e s and choices we now have be fo re us w i t h t h i s new "ag r igene t i c " technology and c h a r t a course t o maximize econo- mic and b i o l o g i c a l d i v e r s i t y i n the ve ry broad- e s t sense o f those terms.

Footnotes

1. Lbvid Pimentel, ''W Genetic Engineer* for Biological Cbntml- k d d n g Eoalogical Risks, " m i u n on Engineered Grganisns in the mvirrrment, CYriLadelphia, l h n q l v a n i a , dme 10-13, 1985.

2. Willian L. Bzcxm, "Sbne Case~yatkns on Changing '2lwIds in Agri- cultural Pmdct icn 9/stens, " Agricultural R?& Institute Qnfem~~, chay Chase, Uxy lmd, Febmary 21-23, 1984.

3- Ihsenberger, "IWmtic R a a l e - M e Fails t o Captivate mdhilU k&shingtcn M, &re 13, 1985, p.A-7.

4. "Plant Grcntt~ &gdatars:Lcw W i l e , High Hopes, r' Ckmical (at. 12, 1984):22-24. -

6. Tim Hammds, W b l i c Attitudes Z t x e r d Food S e t y , " 1984 &ISUI+

er Rends A s s e a & mnfep~nce, Fcvd M e t i n g Institute, Wash. D.C. , mrch 26,1984; and "Kmy M m khrried By Chanicals In Food, .%I Francisx, Chmzi&l, Eud 27, 1984.

7. QTfiae of !khndcgy AEsesrment, Aest U m q m a t Strategies in h o t e d i o n , (-on8 D.C. : U.S. C ~ ~ ~ Z F S S , 1979).

8. B i d .

12. Willian H. El-'Gaughey, "InsPct &stance to the Biological Ih- sscticide Bacillus t h u r i n g i d s , " Senae 229 (7-12-1985):193-4.

l3. Etrbert -, M n s a t n -y, briefing held in o f f i e o f Sterre JdLinek, khshingtcn, D.C., 1984.

Bmce Carlton, "Biological F'edicides: M e t y and 2ged€ ic i t y , "

EW Chemxp (Febmary 20, 1984): 39-40.

S e M w t h AZexander, "Genetic Enginering: Emlogical Clxsqm~ nes, " Issues in Sciaos and !&&nology (Spring 1985): 5768.

Se S.Z. Cbhen et al., ' W x n t i a l far Resticide Cbntaninatim of Csaund keter f m Agricultural h, " in ~~ and M s + o f Pesticide hestes, m i c a n awnical S x i e t y W v n S r i e s 259, W.,D.C.; R.F. E@alding et al . ,ks t ic ide Mnitaring &utnal 14, no. 2 (1980):70-73; and Cass Pete-rstn, "EPA Tightens R?stridicns cn Widely Used Herbicide," kBshingtcn FM, hbwmber 21, 1984.

Barry M i r , "rhircyal Chenical f o r ~ a r n ~ s t o ~ a ~ e ~ e w b y ~ p ~ , ~ ~ M l 5 t ~ & M a l t m y 17, 1984; and Cass F ~ t e r s ~ n , "DA Finds Caner hisk in F m Spray, " k&shingtcn h s t , m y 20, 1984.

P a l C. ''Gnetic FBtentials for Increasing field of

A.T. Mlr G. Fhlt, and M.D. Lillyr I n t e r n a t i d '2lwIds and W- s p f f t i v w in Biotezhrdcgy (Paris, France: GrganiZaticn for E ~ Y + anic m a t i o n and Lkwlopnent, 1982).

24. M p h Ihtdy, "Bi~teohnalcgy:Stahrs~ Forecast, and IS-, I' -8

W d Acadmy of Szkmxs, hbhhgtm, D.C. , H q 1984.

25. &&ua Iederberg, at Brodcings Institution, kbah. D.C., 1-15-85.