FungicidesPast, Present, and Future - ACS Publications - American

7 Fungicides—Past, Present, and Future JAMES G. HORSFALL Downloaded by UNIV OF CALIFORNIA SAN DIEGO on September 2, 2015 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/bk-1977-0037.ch007

The Connecticut Agricultural Experiment Station, Box 1106, New Haven, Conn. 06504

The year 1976 i s surely the year for celebration, f i r s t the b i c e n t e n n i a l of the Nation, then the centennial of the American Chemical Society (ACS). In t h i s context it i s p e r t i n e n t to examine the past, present, and future of the chemicals that are c a l l e d f u n g i c i d e s , the compounds widely used to protect the food of the world from p l a n t disease. I s h a l l l i m i t my remarks to fungicides for food, not for f i b e r . Why Use Fungicides On Food Crops? A b a s i c p r i n c i p l e i n p l a n t pathology i s that fungicides are used for crops that lack n a t u r a l r e s i s t a n c e to the fungus i n v o l v e d . Two notorious examples are Phytophthora infestans on potato and Venturia inaequalis on apple. No farmer would go to the labor and expense to spray h i s potatoes or h i s apples if he could have plants that s u c c e s s f u l l y fight off their fungi. This p r i n c i p l e says f u r t h e r that the amount of fungicide needed or the frequency of a p p l i c a t i o n i s i n v e r s e l y p r o p o r t i o n a l to n a t u r a l resistance. If n a t u r a l resistance i n the host breaks down, farmers often turn to f u n g i c i d e s . A classic example i s the breakdown i n 1970 i n the U . S . of r e s i s t a n c e of maize to Helminthosporium maydis. Farmers turned to zineb i n 1970 even thougn it i s expensive. Had not resistance been r e s t o r e d , zineb might w e l l be widely used on maize by 1976. Wheat i s a curious case. Resistance to the rust disease p e r i o d i c a l l y breaks down i n wheat. As soon as the search discovers a new gene for r e s i s tance i n wheat, a new race of the r u s t fungus appears. This i s the c l a s s i c case of the gene-for113

In Pesticide Chemistry in the 20th Century; Plimmer, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.

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gene h y p o t h e s i s . Despite t h i s p e r i o d i c c o l l a p s e of r e s i s t a n c e i n wheat, no f u n g i c i d e s a r e used i n r e a l l y s i g n i f i c a n t amounts. T h i s i s due t o t h e low cost/benefit ratio. Wheat r e t u r n s such a r e l a t i v e l y low v a l u e p e r h e c t a r e t h a t i t cannot c a r r y the c o s t of an e x p e n s i v e c h e m i c a l c o n t r o l regime. This i s e s p e c i a l l y t r u e s i n c e s o c i e t y , n o t t h e farmer, now b e a r s t h e c o s t o f t h e r e s e a r c h t o produce new v a r i e t i e s , n o t the c o s t o f c h e m i c a l treatment. R i c e i n Japan i s a s p e c i a l case f o r c e r e a l s t h a t n o r m a l l y a r e n o t sprayed w i t h f u n g i c i d e s . The r i c e p r i c e i n Japan i s m a i n t a i n e d h i g h by the government and, hence, farmers can a f f o r d t o spray and a i l o r almost a l l do s p r a y (Ou, 1 ) . F u n g i c i d e s Of The Past In 1776 when t h e N a t i o n was born, we had two u s e f u l f u n g i c i d e s f o r food c r o p s , e l e m e n t a l s u l f u r and copper s u l f a t e . D u r i n g the c e n t u r y b e f o r e t h e f o u n d i n g o f ACS, we added o n l y one more, l i m e - s u l f u r i n 1803 and t h i s was o n l y a v a r i a n t o f e l e m e n t a l sulfur. S i x y e a r s a f t e r ACS was founded, Bordeaux mixture was b o r n o f one o f those a c c i d e n t s that P a s t e u r s a i d happens t o t h e p r e p a r e d mind. In 1876 the y e a r t h a t ACS was founded, t h e F r e n c h wine growers i n a d v e r t e n t l y imported on American r o o t s t o c k s , a new d i s e a s e f o r them, downy mildew. They had been p r o t e c t i n g t h e i r grapes from p i l f e r a g e a l o n g t h e r o a d s i d e s w i t h a horrendousl o o k i n g s l u r r y o f copper s u l f a t e and h y d r a t e d l i m e . P r o f e s s o r A l e x i s M i l l a r d e t , h a v i n g the needed p r e p a r e d mind, was w a l k i n g down a road i n Bordeaux P r o v i n c e d u r i n g t h e h a r v e s t season o f 1882. He n o t i c e d t h a t the t r e a t e d grapes were f r e e o f downy mildew w h i l e the o t h e r s f a r t h e r back from t h e r o a d were i n f e c t e d . And thus was b o r n t h e m a t e r i a l t h a t became t h e h o l y water o f p l a n t p a t h o l o g i s t s who, f o r s i x t y y e a r s o r more, a n n o i n t e d t h e i r c r o p s w i t h i t u n t i l i t was l a r g e l y r e p l a c e d by o r g a n i c s . In 1888 formaldehyde, t h e f i r s t s y n t h e t i c f u n g i c i d e appeared. U n l e s s you count c h l o r o p h e n o l mercury i n 1913, l i t t l e r e a l l y new happened u n t i l 1934 when T i s d a l e and W i l l i a m s o f DuPont r e v e a l e d the d i a l k y l d i t h i o c a r b a m a t e s . They were e x p e n s i v e to make, however, and i t was d e p r e s s i o n days, and so DuPont was s k i t t i s h about t r y i n g t o s e l l them t o farmers when copper s u l f a t e c o u l d be bought f o r 6 c e n t s a pound. The p r i c e b a r r i e r was breached, however, when ;



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H o r s f a l l (2) i n t r o d u c e d c h l o r a n i l f o r legume seed treatment i n the l a t e t h i r t i e s . I t s o l d f o r about $1.50 p e r pound. In 1943 Dimond e t a l (3) i n t r o d u c e d the e t h y l e n e b i s d i t h i o c a r b a m a t e s . "These have gone on to dominate the f u n g i c i d e market f o r a g r i c u l t u r a l crops. In 1943, 2,3-dichloro-l,4-naphthoquinone appeared; i n 1947, 2-her>tadecyl-2-imidazoline; i n 1949, 6 - ( l - m e t h y l h e p t y l ) - 2 , 4 - d i n i t r o p h e n y l c r o t o n a t e ; i n 1952, N - t r i c h l o r o m e t h y l t h i o - 4 - c y c l o h e x e n e - l , 2 - d i c a r boximide ( c a p t a n ) . F u n g i c i d e s Of The

Present

Perhaps, we can b e g i n the p r e s e n t w i t h c a p t a n i n 1952. That g i v e s us a q u a r t e r o f a c e n t u r y . The development o f new compounds exploded i n the fift i e s , as d i d i n s e c t i c i d e s , and n e m a t i c i d e s . The F o r t y F u n g i c i d e s Of The World. By now the w o r l d uses about f o r t y f u n g i c i d e s on i t s c r o p s . The number depends on whether you count the m i x t u r e s and on how you count the v a r i a n t s - say o f the dithiocarbamates. The b e s t l i s t i n g o f f u n g i c i d e s t h a t we know o f i s p u b l i s h e d a n n u a l l y by the M e i s t e r P u b l i s h i n g Company of W i l l o u g h b y , Ohio i n t h e i r Farm Chemicals Handbook. They l i s t the f o l l o w i n g compounds o r types o f compounds as o f f i c i a l l y " r e g i s t e r e d " f o r use on p l a n t s i n the U n i t e d S t a t e s : a l l y l a l c o h o l , ammonium i s o b u t y r a t e , a n t i b i o t i c s , b e n z i m i d a z o l e t y p e s , c a r b o f u r a n , cadmiums, c a p t a n t y p e s , coppers, c a r b o x i n , d e h y d r o a c e t i c a c i d , Dexon (sodium [ 4 - ( d i methylamino) phenyl) diazo sulfonate), diphenyl, dodine, Dyrene ( a n i l a z i n e ) , formaldehyde, g l y o d i n , h a l o g e n a t e d h y d r o c a r b o n s , h y p o c h l o r i t e , Karathane (dinocap t y p e s ) , mercuries, mineral o i l s , n i t r o phenols, organic t i n s , organic a c i d s , pentachloronitrobenzene types, phenols, p y r i m i d i n e s , propylene o x i d e , p y r i d i n e s , p i p e r i d i n e s , q u a t e r n a r y ammoniums, q u i n o l i n o l s , quinones, s u l f u r s , and T e r r a z o l e (5ethoxy-3-trichloromethyl-l,2,4-thiadiazole). The M a j o r Crops Of The World. Mangelsdorf has s a i d t h a t s i n c e the dawn o f h i s t o r y man has used about 3000 s p e c i e s o f p l a n t s f o r food. Perhaps 150 o f these a r e i n w o r l d commerce today, but o n l y 10 p e r c e n t o f these r e a l l y f e e d the p e o p l e o f the world. M a n g e l s d o r f s 15 s p e c i e s i n c l u d e f i v e cer e a l s ; r i c e (Oryza s a t i v a ) , wheat ( T r i t i c u m s p p . ) , maize (Zea mays), sorghum (Sorghum c e r e a l e ) , and n

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b a r l e y (Hordeum v u l g a r e ) ; two sugar p l a n t s : sugar cane (Saccharum o f f i c i n a r u m ) and sugar b e e t ( B e t a vulgaris): three root crops: p o t a t o (Solanum tuberosum), sweet p o t a t o (Ipomea b a t a t a s ) , and c a s s a v a (Manihot e s c u l e n t a ) ; t h r e e legumes: common bean ( P h a s e o l u s v u l g a r i s ) , soybean ( G l y c i n e max), and peanut ( A r a c h i s Jiypogaea); and two t r e e c r o p s : coconut (Cocos n u c i f e r a ) and banana (Musa s p p . ) . In d i s c u s s i n g f u n g i c i d e s we must add some non-food c r o p s ; r u b b e r (Hevea b r a s i l i e n s i s ) , c o f f e e ( C o f f e a spp.), c o t t o n (Uossypium spp.), t e a and tobacco ( N i c o t i a n a tabacum). The M a j o r D i s e a s e s Of The Crops Of The World. The major d i s e a s e s o f r i c e a r e b l a s t and b a c t e r i a l b l i g h t ; wheat, r u s t s and smuts; maize, stem and r o o t r o t s ; b a r l e y , h e l m i n t h o s p o r i a l l e a f spot and r o o t r o t s ; sugar cane, v i r u s e s ; sugar b e e t , v i r u s e s and c e r c o s p o r a l l e a f spot; p o t a t o , l a t e b l i g h t and v i r u s e s ; sweet p o t a t o , stem r o t ; c a s s a v a , mosaic; common bean, v i r u s e s , b a c t e r i a l b l i g h t s , and r o o t r o t s ; soybean, r o o t r o t ; peanut, l e a f spots and r o o t r o t ; coconut, p r a c t i c a l l y none; banana, w i l t and S i g o t o k a ; rubber, l e a f b l i g h t ; c o f f e e , r u s t ; c o t t o n , w i l t and r o t s o f s e e d l i n g s and b o l l s ; t o b a c c o , b l u e mold; t e a , b l i s t e r b l i g h t . The massive tonnages o f f u n g i c i d e s used i n the w o r l d a r e a p p l i e d t o f o l i a g e d i s e a s e s o f the c r o p s w i t h h i g h v a l u e p e r a c r e - banana, p o t a t o , a p p l e , c i t r u s , v e g e t a b l e s , t o b a c c o , peanut, c o f f e e , t e a , rubber. Few f u n g i c i d e s go on the f o l i a g e o f t h e c e r e a l s (except r i c e i n J a p a n ) , legumes, and c o t t o n . The r o o t c r o p s g e n e r a l l y remain a l o o f from f u n g i c i d a l treatment. Yes, t h e w o r l d t r e a t s seeds f o r damping o f f , and t r e a t s s o i l i n seedbeds and greenhouses f o r r o o t r o t , b u t seldom i n t h e f i e l d . There i s some s p r a y i n g o f c o t t o n seed as i t i s planted. The w o r l d uses some f u n g i c i d e s f o r seed borne d i s e a s e s l i k e t h e c e r e a l smuts and i t uses some f u n g i c i d e s t o p r e v e n t decay o f f r u i t s and v e g e t a b l e s enroute t o market. The tonnage i s s m a l l , however. D e s p i t e t h e g r e a t a r r a y o f f o r t y f u n g i c i d e s , one i s d e p r e s s e d t o see how many o f the w o r l d s major plant diseases are s t i l l not properly c o n t r o l l e d b a c t e r i a l d i s e a s e s , v i r a l d i s e a s e s , r o o t r o t s , and wilts. The c h a l l e n g e beckons. Chemotherapy i s one p o s s i b l e answer t o t h e challenge. T r e a t the p l a n t from the i n s i d e and n o t


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on t h e o u t s i d e o n l y as i n t h e p a s t . c a l l t h i s "inneretherapy".


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The Germans

The D r i v e F o r Chemotherapy. Chemotherapy o f p l a n t d i s e a s e has advanced r a p i d l y i n r e c e n t y e a r s f o l l o w i n g a slow s t a r t i n t h e ' f o r t i e s . I t has gone so f a r t h a t we now have a whole book ( 5 ) d e v o t e d t o i t and a r e v i s i o n underway a f t e r o n l y t h r e e y e a r s . Perhaps t h e f r o n t - r u n n i n g chemotherapeutant i s benomyl and i t s b e n z i m i d a z o l e r e l a t i v e s which have a c h i e v e d d r a m a t i c r e s u l t s on v a s c u l a r d i s e a s e s . Other s e l e c t i v e t h e r a p e u t a n t s a r e c a r b o x i n , s e v e r a l p y r i m i d i n e s , t r i f o r i n e , s e v e r a l m o r p h o l i n e s , 6a z a u r a c i l , a z e p i n e s , p h e n y l t h i o u r e a s , c h l o r o n e b , and others. L i k e any new f i e l d , chemotherapy o f p l a n t d i sease has i t s semantic problems. When we h e l p e d i n i t i a t e i t i n 1940, we c a l l e d i t chemotherapy i n l i n e with our medical c o n f r e r e s . Literally i t means, o f c o u r s e , c h e m i c a l c u r e , b u t i t i s g i v e n a c o n n o t a t i o n o f i n t e r n a l t h e r a p y as w e l l . There i s a s t r o n g tendency, p a r t i c u l a r l y i n B r i t a i n t o l a b e l i t s y s t e m i c f u n g i c i d e . " The semantic p r o b l e m h e r e i s t h a t n o t a l l chemotherapeutants a r e s y s t e m i c fungicides. Even benomyl, t h e l e a d i n g c o n t e n d e r , i s not a t r u e f u n g i c i d e . It i s a fungistat. Chemotherapy o f p l a n t d i s e a s e has a b u i l t - i n weakness, n o t c o n f r o n t i n g t h a t o f a n i m a l t h e r a p y . P l a n t s have no phagocytes t o c l e a n up t h e s t r a g g l e r s t h a t a r e m i s s e d by the t h e r a p e u t a n t . Penicillin i s only b a c t e r i o s t a t i c . I t does n o t k i l l t h e b a c t e r i a but i t keeps them few enough f o r l o n g enough t o g i v e t h e phagocytes a chance. Benomyl does n o t enjoy the b e n e f i t of phagocytes. I t has a p a r t i a l l y compensating advantage, however. I t i s not excreted by the k i d n e y s and i t t h e r e f o r e l a s t s l o n g e r i n t h e plant. A l e s s s t a b l e compound would be l e s s e f f e c tive. n

The Rachel Carson Syndrome. In June 1962 i n the m i d d l e o f one o f the w o r l d ' s g r e a t c i t i e s and f a r from t h e farm, t h e r e appeared i n one o f t h e w o r l d ' s s o p h i s t i c a t e d j o u r n a l s (The New Y o r k e r ) , an a r t i c l e t h a t s e t t h e a g r i c u l t u r a l segment o f t h e w o r l d on f i r e . I t was w r i t t e n by a l a d y m i s s i o n a r y named Rachel Carson. L a t e r i n 1962 i t was expanded i n t o a book, S i l e n t S p r i n g ( 6 ) . She s a i d t h a t t h e w o r l d was s u f f o c a t i n g i n a p o i s o n o u s r a i n o f p e s t i c i d e s and she accused t h e farmers o f p o i s o n i n g h e r food. The s c a r e she s e t i n motion has spread around


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the g l o b e . teeth.

C o n s t r a i n t s have sprung up

THE

like

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dragons'

The Rapid R i s e In C o n s t r a i n t s . Her book changed most o f the r u l e s o f the game i n d e v e l o p i n g and u s i n g f u n g i c i d e s . For i n s t a n c e , c h l o r a n i l (Spergon; was f i r s t t e s t e d on spores i n the l a b o r a t o r y i n 1938 ( 2 ) . By A p r i l 1940, farmers o f New York S t a t e were u s i n g i t by the hundred weight and by 1941 by the t o n to t r e a t pea and l i m a bean seed to p r o t e c t a g a i n s t seed decay. That was two y e a r s from l a b o r a t o r y to f i e l d . And now i t takes s i x o r seven y e a r s to go the same d i s t a n c e . In the meantime uncounted numbers o f r a t s and mice, even dogs, must be s a c r i f i c e d on the C a r s o n a l t a r . When lawy e r s and c o n t r o l o f f i c i a l s by the s c o r e get i n t o the a c t , d e v e l o p m e n t a l c o s t s shoot sky h i g h and the end i s by no means i n s i g h t . The c o n s t r a i n t s have i n c r e a s e d the h a z a r d s o f f a r m i n g because d i s e a s e s a r e now more d i f f i c u l t to control. Carson's book has spawned a h o s t o f "new e c o l o g i s t s ' who e n j o y b a i t i n g farmers by s a y i n g t h a t they p o l l u t e the environment and the food o f man. Farmers a r e f i g h t i n g back. A bumper s t i c k e r on a farmer's t r u c k now r e a d s , " I f you c r i t i c i z e a g r i c u l t u r e , don't t a l k w i t h y o u r mouth f u l l . " The mouths of the new e c o l o g i s t s are a l l f u l l . D e s p i t e a l l the a l l e g e d p o i s o n s i n the food, stomach c a n c e r i s d e c l i n i n g ; sons and daughters a r e growing t a l l e r than t h e i r p a r e n t s ; and a t h l e t e s c o n t i n u a l l y break world's r e c o r d s . The DDT i n the f a t o f the a t h l e t e s must be r e s p o n s i b l e f o r the new records ! ! The Carson syndrome has had important impacts on the s c i e n t i f i c base o f f u n g i c i d e s . For example, a study o f the membership l i s t s o f the American P h y t o p a t h o l o g i c a l S o c i e t y shows t h a t the number o f p l a n t p a t h o l o g i s t s who work w i t h f u n g i c i d e s i s falling. 1

The S e a r c h For S e l e c t i v i t y . I had the honor o f s e r v i n g on a committee a p p o i n t e d a t the r e q u e s t o f P r e s i d e n t John F. Kennedy to examine the s i g n i f i cance of Carson's book. Our r e p o r t t o him i n the s p r i n g o f 1963 was e n t i t l e d "The Use o f P e s t i c i d e s " (7). Among o t h e r t h i n g s , we recommended t h a t p e s t i c i d e s , i n c l u d i n g f u n g i c i d e s , be made more s e l e c t i v e . And they were. B i a s t i n (pentachlorobenzyl alcohol) i s select i v e f o r r i c e b l a s t , Dexon (sodium [ 4 - ( d i -



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methylamino) phenyl] • d i a z o s u l f o n a t e ) f o r Pythium, p e n t a c h l o r o n i t r o b e n z e n e f o r R h i z o c t o n i a , and c a r boxin f o r Basidiomycetes. S e l e c t i v i t y i s b r i l l i a n t l y d i s p l a y e d by a m u l t i p l i c i t y o f compounds developed f o r the c o n t r o l of powdery mildews. For 148 y e a r s from 1803 u n t i l 1951 s u l f u r was the o n l y s i g n i f i c a n t f u n g i c i d e f o r powdery mildew. In 1949' a new f u n g i c i d e appeared w i t h the p u b l i c a t i o n of 6 - ( l - m e t h y l h e p t y l ) - 2 , 4 d i n i t r o - p h e n y l c r o t o n a t e ( 8 ) . Two y e a r s l a t e r Yarwood r e p o r t e d (9) i t s anti-powdery mildew p r o p e r ties. I t went on to worldwide usage and thus stimulated a vast search f o r others. Now we have many e f f e c t i v e compounds, i n c l u d i n g benomyl, b i n a p a c r y l , dodemorph, f o l p e t , p a r i n o l , p i p e r a l i n , pyrazophos, t h i o p h a n a t e , t r i d e m o r p h , t r i f o r i n e , and o t h e r s . The R i s e Of Fungus R e s i s t a n c e . The d r i v e f o r s e l e c t i v i t y t h a t i s urged on by the Carson p r e s s u r e has exaggerated a s m a l l t r e n d t h a t had a l r e a d y shown up b e f o r e Carson. Fungi had developed r e s i s t a n c e t o some of the s e l e c t i v e f u n g i c i d e s . When H o r s f a l l p u b l i s h e d (2) h i s second book s i x y e a r s ahead o f Carson, he had d i f f i c u l t y i d e n t i f y i n g any r e s i s t a n t fungi. A few were noted, but w i t h i n f i v e v e a r s a f t e r Carson, Georgopoulos and Z a r c o v i t i s demonstrated d r a m a t i c a l l y that s e l e c t i v i t y i s a t r i c k y s o l u t i o n to a v e r y d i f f i c u l t problem posed so nonchalantly The b i o l o g y i s f a i r l y s i m p l e . The more s e l e c t i v e we make our f u n g i c i d e s , the fewer the b l o c k s i n the p a t h of the fungus, and the e a s i e r i t can f i n d a bypass around the b l o c k . However p r o m i s i n g a compound may be as an o r i g i n a l k i l l e r o f the p e s t fungus, i t s use may be eroded by r e s i s t a n c e almost by the time i t i s a b l e to pass through a l l the maze of o f f i c i a l approval. The r a p i d b i o l o g i c a l e r o s i o n of new compounds i s v e r y d i s c o u r a g i n g to those who must develop them to c o n t r o l p l a n t d i s e a s e . F u n g i c i d e s F o r The

Future

We a l l want answers to the q u e s t i o n , where n e x t ? Where does f u n g i c i d e r e s e a r c h go now? I agree w i t h the D a n i s h h u m o r i s t , V i c t o r Borge, who has s a i d , " F o r e c a s t i n g i s a d i f f i c u l t b u s i n e s s , esp e c i a l l y f o r the f u t u r e " . S t i l l , we must l o o k ahead. The T a c t i c s And S t r a t e g y Of D i s c o v e r y . By and


120

PESTICIDE C H E M I S T R Y IN

THE

20TH

CENTURY

l a r g e the world's f u n g i c i d e s have come from the i n d u s t r i a l c o u n t r i e s o f U.S.A., B r i t a i n , S w i t z e r l a n d , German and Japan. I t seems r e a s o n a b l e t o say t h a t the development o f new f u n g i c i d e s by i n d u s t r y i s becoming an i n c r e a s i n g l y more d i f f i c u l t b u s i n e s s . There are a t l e a s t t h r e e reasons f o r t h i s . (1) The r e g u l a t o r s are i n t r o d u c i n g an e v e r i n c r e a s i n g number o f t e s t s t h a t must be done o v e r an e v e r - i n c r e a s i n g number o f y e a r s and o v e r an e v e r i n c r e a s i n g number o f t e s t organisms. This dimini s h e s the l i k e l i h o o d o f f i n d i n g a u s e f u l compound and m u l t i p l i e s the c o s t . As a r e s u l t the s m a l l e r l e s s w e l l c a p i t a l i z e d companies are d e s e r t i n g the f i e l d and t h o s e t h a t remain seem to be spending a l a r g e r p r o p o r t i o n o f t h e i r time d e f e n d i n g the compounds they have a l r e a d y marketed o r a r e h o p i n g to market, and p r o p o r t i o n a l l y l e s s time on e x p l o r i n g . (2) S i n c e enormous numbers o f compounds have a l r e a d y been made and s c r e e n e d , the odds o f f i n d i n g a new one seem to be d i m i n i s h i n g (von Rumker e t a l , 11). (3) The c o m p e t i t i o n f o r o l d markets i s keen and new markets seem t o d e v e l o p s l o w l y . Some w i l l say, " L e t the p u b l i c s e c t o r of s o c i e t y take o v e r the j o b . " T h i s won't s o l v e the c o s t problems o f r e g u l a t i o n o r the p r o b a b i l i t y of f i n d i n g new and u s e f u l s t r u c t u r e s , and b e s i d e s , s o c i e t y does not do w e l l i n the m a n u f a c t u r i n g b u s i n e s s . S o c i e t y may w e l l be f o r c e d , however, t o take o v e r the t e r r i b l e c o s t s o f s a f e t y determination. That we a r e s t i l l g r e a t l y c h a l l e n g e d i s w i t nessed by the l a r g e number o f u n c o n t r o l l e d f u n g a l d i s e a s e s , not to mention v i r a l and b a c t e r i a l d i seases. The r o o t r o t s , the v a s c u l a r w i l t s , and the c e r e a l r u s t s comprise the major c h a l l e n g e s . We p r o b a b l y w i l l f i n d the g r e a t e s t s u c c e s s by t e s t i n g c a n d i d a t e compounds on the p l a n t s themselves. This w i l l encourage s e l e c t i v i t y and thus runs a s e v e r e r i s k of developing r e s i s t a n c e .


t

Cooperate With P l a n t B r e e d e r s . S u r e l y the odds run h e a v i l y a g a i n s t s u c c e s s i n f i n d i n g t h e r a p e u t a n t s t h a t can escape the r e s i s t a n c e problem, but p l a n t b r e e d e r s f a c e h a z a r d s as g r e a t . Perhaps, we s h o u l d j o i n hands w i t h the b r e e d e r s . Perhaps we c o u l d o u t w i t the fungus by combining a r e s i s t a n c e gene w i t h a chemotherapeutant. T h i s would m u l t i p l y the odds i n our f a v o r . Cooperate With P h y s i o l o g i s t s .

Another p o s s i -


7.

HORSFALL

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b i l i t y i s t o j o i n hands w i t h those who study t h e p h y s i o l o g y o f d i s e a s e . P l a n t s do have b i o c h e m i c a l and p h y s i c a l means f o r p r o t e c t i n g themselves from d i s e a s e a t t a c k . Here i s a p o t e n t p o s s i b i l i t y o f a s y n e r g i s t i c approach. S t i l l another p o s s i b i l i t y i s t o search f o r compounds t h a t a c t on t h e f e a t u r e s t h a t c h a r a c t e r i z e and d i s t i n g u i s h f u n g i from h i g h e r p l a n t s and humans. A n t i d i f f e r e n t i a t i o n Compounds. Fungi d i f f e r ent iaFêTli$îêrr~^ from t h e i r h o s t s and from humans. F o r example, f u n g i have w a l l s o f c h i t i n . They reproduce through s p o r e s . Humans and h i g h e r p l a n t s do n o t . Very few s c r e e n s have been d e l i b e r a t e l y developed t o e x p l o i t t h e s e differences. We have d i s c o v e r e d enough compounds a c c i d e n t a l l y t o be a b l e t o say t h a t p o s s i b i l i t i e s e x i s t , however. G r i s e o f u l v i n , f o r example, c u r l s and t w i s t s t h e germ tubes so t h a t they a r e u n a b l e to i n f e c t t h e t i s s u e . Polyoxin i n t e r f e r e s with c h i t i n s y n t h e s i s . B i a s t i n p r e v e n t s an a p p r e s s o r i u m of t h e r i c e pathogen from s e n d i n g down an i n f e c t i o n peg i n t o t h e l e a f , and so i t goes. In o u r l a b o r a t o r y we have developed a h i g h l y e f f e c t i v e and r a p i d s c r e e n t o p i c k o u t a n t i s p o r u l a n t s ( 1 2 ) . We c a n use the same t e c h n i q u e s f o r p i c k i n g o u t a n t i c o n i d i o p h o r e compounds ( 1 3 ) . Summary We- d i s c u s s t h e major c r o p s o f t h e w o r l d and t h e i r major d i s e a s e s and i n d i c a t e how d i s c o u r a g i n g l y few a r e those t h a t c a n now be a d e q u a t e l y c o n t r o l l e d by f u n g i c i d e s o r o t h e r w i s e . We l i s t t h e world's 40 f u n g i c i d a l t y p e s . The e n v i r o n m e n t a l i s t s a r e a d d i n g more and more c o n s t r a i n t s o f more and more c o m p l e x i t y on t h e p r o c e s s o f d e v e l o p i n g new compounds. They a r e i n s i s t i n g on s e l e c t i v i t y . This l e a d s i n t o fungus r e s i s t a n c e . T h i s lowers t h e odds of e v e n t u a l s u c c e s s and d i s c o u r a g e s t h e i n n o v a t o r s . We urge r e s e a r c h on s c r e e n i n g p r o c e d u r e s so t h a t they may be more d i r e c t l y aimed a t t h e f u n g a l l i f e p r o c e s s e s ( c h i t i n s y n t h e s i s , f o r example) t h a t a r e d i f f e r e n t from h o s t o r human rocesses. Literature 1.

Cited

Ou, S . H . "Rice D i s e a s e s . " 368 p p . wealth Mycol. Inst. Kew, S u r r e y , 1972.

CommonEngland.



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2. 3. 4.


5. 6. 7. 8. 9. 10. 11. 12. 13.

CENTURY

H o r s f a l l , J.G. " P r i n c i p l e s of F u n g i c i d a l Action." 279 pp. Chronica Bot. Co. Waltham, Mass. 1956. Dimond, A.E., Heuberger, J.W., and H o r s f a l l , J.G. Phytopathol. 1943. 33:1005-1007. Mangelsdorf, P.C. Proc. Nat. Acad. S c i . U . S . A . 1966. 56: 370-375. Marsh, R.W. E d i t o r . "Systemic F u n g i c i d e s . " 321 pp. Halstead Press. New York. 1972. Carson, Rachel. " S i l e n t S p r i n g . " 368 pp. Houghton Mifflin Co. Boston, Mass. 1962. P r e s i d e n t ' s Science Advisory Committee. "The Use of P e s t i c i d e s . " The White House. Washington, D . C . 1963. R i c h , S. and H o r s f a l l , J.G. Phytopathol. 1949. 39:19. Yarwood, C.E. Proc. IInd Int. Congr. of Crop P r o t e c t i o n . 1951. p. 1-22. Georgopoulos, S . G . and Z a r a c o v i t i s , C. Ann. Rev. Phytopathol. 1967. 5: 109-130. Von Rumker, R., Guest, H . R . , and Upholt, W.M. Bioscience. 1970. 20: 1004-1007. Lukens, R.J. Phytopathol. 1960. 50: 867-868. Lukens, R.J. and H o r s f a l l , J.G. 1971. Phyto pathol. 1971. 61:13.


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