Focus on Weed Control: Herbicides as Weed Control Agents: State of the Art: I. Weed Control Research and Safener Technology: The Path to Modern Agriculture

The purpose of modern industrial herbicides is to control weeds. The species of weeds that plague crops today are a consequence of the historical past, being related to the history of the evolution of crops and farming practices. Chemical weed control began over a century ago with inorganic compounds and transitioned to the age of organic herbicides. Targeted herbicide research has created a steady stream of successful products. However, safeners have proven to be more difficult to find. Once found, the mode of action of the safener must be determined, partly to help in the discovery of further compounds within the same class. However, mounting regulatory and economic pressure has changed the industry completely, making it harder to find a successful herbicide. Herbicide resistance has also become a major problem, increasing the difficulty of controlling weeds. As a result, the development of new molecules has become a rare event today.Modern industrial herbicide research begins with the analysis and definition of research objectives. A major part of this lies in the definition of economically important weeds in major arable crops (Kraehmer, 2012). Weed associations change slowly over time. It is important, therefore, to foresee such changes. Today’s weed associations result from events in the distant past. They are associated with the history of crops and the evolution of farm management. In Europe and the Americas, some large-acre crops such as winter oilseed rape and spring oilseed rape (canola), both derived from Brassica spp., and soybean (Glycine max) have attained their current importance only within the last 100 years. Other Old World crops, such as cereals, have expanded over a very long time span and were already rather widespread in Neolithic times (Zohary et al., 2012). The dominance of crop species in agricultural habitats only left room for weed species that could adapt to cultivation technologies. Changes in crop management and the global weed infestation have happened in waves. A major early factor in Europe was presumably the grain trade in the Roman period (Erdkamp, 2005). The Romans spread their preferred crops and, unintentionally, associated weed seeds throughout Europe, Asia, and Africa. A second wave of global vegetation change started in the 16th century after the discovery of the Americas. Crops and weeds were distributed globally by agronomists and botanists. Alien species started to spread on all continents. A third phase can be seen in the 19th century with the industrialization of agriculture and the breeding of competitive crop varieties. The analysis of weed spectra in arable fields grew from this historical background. Weeds are plants interfering with the interests of people (Kraehmer and Baur, 2013), which is why they have been controlled by farmers for millennia.Chemical weed control began just about a century ago with a few inorganic compounds, such as sulfuric acid, copper salts, and sodium chlorate (Cremlyn, 1991). The herbicidal activity of 2,4-dichlorophenoxyacetic acid was detected in the 1940s (Troyer, 2001). Büchel et al. (1977) and Cremlyn (1991), Worthington and Hance (1991). Targeted herbicide research began in the 1950s. In the early days, herbicide candidates progressed from screens purely on the basis of their having biology that would satisfy farmers’ requirements. Mode of action (MoA) studies did not play a major role in the chemical industry prior to the 1970s. Analytical tools were developed and the rapid elucidation of plant pathways and in vitro-based screen assays were used from the 1980s onward. However, in the 1990s and beyond, ever-increasing regulatory and economic pressures have changed the situation of the industry completely, and to satisfy the new requirements, selection criteria beyond biological activity have needed to be applied. Herbicide resistance in weeds has developed into a more serious problem that now constrains the application of certain types of herbicides in some markets. Finally, the introduction of crops resistant to cheap herbicides and of glyphosate-resistant soybean, in particular, took value out of the market and resulted in an enormous economic pressure on the herbicide-producing industry. As a result of this changing and more difficult landscape, the development of new molecules is now a rare event.

Table I.

History of chemical weed control innovationsPost, Postemergence application; Pre, preemergence application, based on data from Cremlyn (1991), Worthington and Hance (1991), Büchel et al. (1977), Herbicide Resistance Action Committee (www.hracglobal.com), and others.

MoA, Target Site	Chemical Family	Examples	Use	Earliest Reports
Unspecific	Inorganic herbicides	H2SO4, Cu2SO4, FeSO4, NaAsO2	Total	1874
Uncouplers	Dinitrophenoles	dinitro-ortho-cresol	Post, dicots	1934
Auxins	Aryloxyalkanoic acid derivatives	2,4-Dichlorophenoxyacetic acid	Post, dicots in cereals	1942
Microtubule organization	Arylcarbamates	Propham, chloropropham	Pre, monocots in various crops	1946
Lipid synthesis	Chloroaliphatic acids	TCA, dalapon	Pre, monocots in various crops	1947
	Thiocarbamates	EPTC, triallate	Pre, monocots and dicots in various crops	1954
PSII	Arylureas	Monuron, diuron, isoproturon, linuron	Pre and Post, monocots and dicots in various crops	1951
	1,3,5-Triazines	Atrazine, simazine	Pre and Post, broad spectrum in corn	1952
	Pyridazines	Chloridazon	Pre, dicots in sugar beet	1962
	Uracils	Bromacil, terbacil, lenacil	Soil applied, broad spectrum in various crops	1963
	Biscarbamates	Phenmedipham	Post, dicots in sugar beet	1968
	1,2,4-Triazinones	Metribuzin	Pre in soybean	1971
Very-long-chain fatty acid biosynthesis	Chloroacetamides	Allidochlor, alachlor	Pre, monocots and dicots	1956
PSI	Bipyridyliums	Diquat, paraquat	Nonselective	1958
Protoporphyrinogen oxidase	Diphenyl ethers	Nitrofen, acifluorfen	Pre and Post, various crops	1960
	Oxadiazoles	Oxadiazon	Rice, nonselective	1969
Microtubule assembly	Dinitroanilines	Trifluralin, pendimethalin	Pre against monocots and dicots	1960
Cellulose biosynthesis	Nitriles	Dichlobenil	Plantations	1960
5-Enolpyruvylshikimate 3-phosphate synthase	Glys	Glyphosate	Post, nonselective	1971
Phytoene desaturase	Pyridazinones	Norflurazon	Pre and Post in cotton	1973
ACCase	Aryloxyphenoxy propanoates	Diclofop, fluazifop	Post, grasses	1975
	Cyclohexane diones	Alloxydim, sethoxydim	Post, grasses	1976
Gln synthetase		Glufosinate	Nonselective	1981
AHAS or ALS	Sulfonylureas	Chlorsulfuron, metsulfuron	Monocots and dicots in various crops	1982
	Imidazolinones	Imazapyr, imazethapyr	Nonselective or selective in soybean	1983
	Pyrimidinyl benzoates	Bispyribac sodium	Rice	1994
HPPD		Pyrazolynate, sulcotrione	Various crops, monocots and dicots	1984

Open in a separate windowThis article is structured into three main topics. First, it provides an historic overview of the development of weed control history and of screening tools over the past 100 years. Thereafter, we concentrate on the use of MoA studies as a tool for optimizing chemical structures based upon knowledge of their receptors. Finally, we review the invention and use of safener technologies as a tool for improving the crop selectivity of herbicides. In a companion review (Kraehmer, et al., 2014), we address the serious challenges that farmers now face because of the evolution of herbicide resistance in weeds and the types of innovations that are urgently required.