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Rachel Carson catalyzed the global environmental movement with her 1962 book Silent Spring.

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Rachel Carson | Biography, Books, & Facts

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Rachel Carson, American biologist well known for her writings on environmental pollution and the natural history of the sea. She alerted the world to the dangers of pesticides and pollution in her prophetic Silent Spring (1962), which was first serialized in The New Yorker and then became a best sel…

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her early life

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Rachel Carson, 1940. US Fish and Wildlife Service employee photo.
Courtesy US Fish and Wildlife Service.

Rachel Louise Carson was a biologist, writer, and environmental activist. Most of Carson's writing expressed her love of nature and concern for future generations. With language that was both poetic and compelling, she inspired people to become interested in the natural world. Her book Silent Spring alerted the public to the dangers of using chemical pesticides carelessly. Carson's work influenced the global environmental and conservation movements.

Early Life and Education

Carson was born on May 27, 1907. She grew up in rural Springdale, Pennsylvania, and spent her childhood exploring the hills and fields surrounding her family's farm.[1] Her mother, Maria McLean, taught her about the local wildlife. Since childhood, Carson had wanted to become a writer.

In 1925, she began studying English at Pennsylvania College for Women. She later switched to biology. During a summer research project in Woods Hole, Massachusetts, Carson encountered the sea for the first time. It would become the focus of much of her work. During the 1930s, Carson studied and taught biology and zoology at Johns Hopkins University and the University of Maryland. Unfortunately, she could not earn enough money as a PhD student to support her family during the Great Depression. She left her program to get a job with better pay.

Early Career and Writing

In 1935, Carson started working in the public education department of the U.S. Bureau of Fisheries (now the U.S. Fish and Wildlife Service). Her job enabled her to combine her talents as a writer and biologist. She interpreted scientific information for the public in radio programs and brochure series. Her radio program, "Romance Under the Waters," discussed marine life. She moved up in the ranks, eventually becoming editor-in-chief of all FWS publications.

At the same time, Carson was publishing her own work. While sales of her first book Under the Sea-Wind (1941) were disappointing, her second work The Sea Around Us (1951) had better success. It stayed on the New York Times bestseller list for a record-breaking 86 weeks and won the National Book Award for Non-fiction. In her acceptance speech, Carson explained:

"The aim of science is to discover and illuminate truth...If there is poetry in my book about the sea, it is not because I deliberately put it there, but because no one could write truthfully about the sea and leave out the poetry."

Relationship with Dorothy Freeman

Shortly after Carson published The Sea Around Us, she received a letter from a woman named Dorothy Freeman. Freeman spent her summers on an island off the coast of Maine.[2] After reading Carson's book, Freeman discovered Carson had a cottage there too and decided to write to her. The women became very close.

Carson and Freeman's correspondence from 1953 to 1964 provides an intimate look into their relationship. Each envelope they sent each other contained two letters. The first was to share with Freeman's husband or Carson's mother; the second was private and intended to be destroyed. In these letters, Carson expressed her appreciation for Freeman as a "dearly loved friend" who supported her and her writing. In a 1954 letter, Carson wrote:

"It is quite necessary for me to know that there is someone who is deeply devoted to me as a person, and who also has the capacity and the depth of understanding to share, vicariously, the sometimes crushing burden of creative effort, recognizing the heartache, the great weariness of mind and body, the occasional black despair it may involve-someone who cherishes me and what I am trying to create, as well."

Carson was an intensely private person. Before her death, she and Freeman destroyed about 500 of their letters. In 1995, Freeman's granddaughter published the remaining letters in an edited collection called Always, Rachel. These letters reveal how Freeman helped to sustain Carson through some of her biggest challenges. During this period, Carson cared for her ailing mother, adopted her orphaned grandnephew, and published Silent Spring.

Silent Spring

Silent Spring is widely considered Carson's most influential work. It was first published in three parts in The New Yorker in June 1962 and then released as a book. Carson wrote the book at her home in Silver Spring, Maryland. It is now a National Historic Landmark.[3] Silent Spring warned Americans against the "indiscriminate use" of chemical pesticides, including Dichlorodiphenyltrichloroethane (DDT). The title referred to the threat of a world without birdsong if DDT use continued.

During World War II, chemical companies sold DDT to the military to kill lice. After the war, companies began selling it for use on farms and gardens. Carson grew concerned after reading government reports. DDT hadn't been tested for civilian use and seemed to be killing wildlife other than insects. Carson pitched an article about the subject to Readers' Digest, but the magazine rejected her. Nearly twenty years later, she released Silent Spring.

Carson urged the government to do more extensive research into environmental issues. She wanted the public to make fully informed decisions about health and safety. In Silent Spring, she emphasized the interconnectedness of the natural environment as a whole:

"Can anyone believe it is possible to lay down such a barrage of poison on the surface of the earth without making it unfit for all life? They should not be called 'insecticides' but 'biocides.'"

Silent Spring sparked a national controversy over the use of pesticides. Chemical companies worried about how Carson's writing would impact their profits and tried to discredit her. They claimed that banning pesticides would allow insects to dominate American agriculture and spread disease. Carson refused to back down.

Legacy

While writing Silver Spring, Carson had been diagnosed with breast cancer. Her symptoms and medical treatments hindered her work on the book. She underwent multiple surgeries and radiation therapy, but the cancer continued to spread. After Silent Spring was published, Carson kept her illness a secret from everyone but her publisher and Freeman. They feared that the chemical companies would use it against her.

Despite her deteriorating health, Carson continued to advocate for stronger environmental regulations. In 1963, she testified before the Senate Committee on Commerce. She urged them to require companies to include labels about preventing environmental damage on their products.

On April 14, 1964, Carson died in her home in Silver Spring, Maryland. Before her death, she lamented to Freeman that she would be remembered for Silent Spring, not her love of the sea.

Throughout her life, Carson shared her love of the natural world with others. Her writing raised awareness about environmental issues around the world. Silent Spring became an international bestseller. In the U.S., Carson's work led to the establishment of the Environmental Protection Agency and the first Earth Day celebration in 1970. Silent Spring influenced several federal conservation policies, including the ban of DDT in 1972.

Notes

[1] The Rachel Carson Homestead in Springdale, Pennsylvania was listed in the National Register of Historic Places in 1976.
[2] The U.S. Fish and Wildlife Service established the Rachel Carson National Wildlife Refuge along the coast of Maine in 1966.
[3] The Rachel Carson House in Silver Spring, Maryland became a National Historic Landmark in 1991.

Carson, Rachel. "A Battle in the Clouds." St. Nicholas 45, no. 11 (September 1918): 1048. Yale University Library Digital Collections. Accessed October 1, 2021. https://collections.library.yale.edu/catalog/2003110.
Carson, Rachel. "From Carson's remarks at her acceptance of the National Book Award for Nonfiction." Rachel Carson Excerpts Continued. U.S. Fish and Wildlife Service. Last updated February 5, 2013. https://www.fws.gov/refuge/Rachel_Carson/about/rachelcarsonexcerpts2.html.
Lear, Linda. Rachel Carson: Witness for Nature. New York: Henry Holt & Company, 1994.
Leonard, Jonathan Norton. "Rachel Carson Dies of Cancer; 'Silent Spring' Author Was 56." New York Times. April 15, 1964. https://www.nytimes.com/1964/04/15/rachel-carson-dies-of-cancer.html.
Lepore, Jill. "The Right Way to Remember Rachel Carson." The New Yorker. Published March 19, 2018. Accessed September 14, 2021. https://www.newyorker.com/magazine/2018/03/26/the-right-way-to-remember-rachel-carson.
Thomas, P. L. "Speaking Truth to Power: The Legacies of Rachel Carson." The English Journal 103, no. 6 (July 2014): 81-84. JSTOR. Accessed September 14, 2021. https://www.jstor.org/stable/24484389.
U.S. Fish and Wildlife Service. "Rachel Carson Biography." Rachel Carson National Wildlife Refuge. Last updated February 5, 2013. https://www.fws.gov/refuge/rachel_carson/about/rachelcarson.html.

The content for this article was researched and written by Jade Ryerson, an intern with the Cultural Resources Office of Interpretation and Education.

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Rachel Carson (U.S. National Park Service)

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Rachel Louise Carson was a biologist, writer, and environmental activist. Most of Carson's writing expressed her love of nature and concern for future generations. With language that was both poetic and compelling, she inspired people to become interested in the natural world. Her book Silent Spring alerted the public to the dangers of using chemical pesticides carelessly.

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Although they will probably always be less celebrated than wars, marches, riots, or stormy political campaigns, books have at times been the most powerful influencer of social change in American life. Thomas Paine's Common Sense galvanized radical sentiment in the early days of the Revolution; Uncle Tom's Cabin by Harriet Beecher Stowe roused the North's antipathy to slavery in the decade leading up to the Civil War; and Rachel Carson's Silent Spring, which in 1962 exposed the hazards of the pesticide DDT, eloquently questioned humanity's faith in technological progress and helped set the stage for the environmental movement.

Carson, a renowned nature author and a former marine biologist with the U.S. Fish and Wildlife Service, or FWS, was uniquely equipped to create so startling and inflammatory a book. A native of rural Pennsylvania, she had grown up with an enthusiasm for nature matched only by her love of writing and poetry. The educational brochures she wrote for FWS, as well as her published books and magazine articles, were characterized by meticulous research and a poetic evocation of her subject.

"Things go out of kilter"

Carson was happiest writing about the strength and resilience of natural systems. Her books Under the Sea Wind, The Sea Around Us (which stayed on the New York Times best-seller list for 86 weeks), and The Edge of the Sea were hymns to the interconnectedness of nature and all living things. Although she rarely used the term, Carson held an ecological view of nature, describing in precise yet poetic language the complex web of life that linked mollusks to seabirds to the fish swimming in the ocean's deepest and most inaccessible reaches.

DDT, the most powerful pesticide the world had ever known, exposed nature's vulnerability. Unlike most pesticides, whose effectiveness is limited to destroying one or two types of insects, DDT was capable of killing hundreds of different kinds at once. Developed in 1939, it first distinguished itself during World War II, clearing South Pacific islands of malaria-causing insects for U.S. troops while being used as an effective delousing powder in Europe. Its inventor was awarded the Nobel Prize.

When DDT became available for civilian use in 1945, there were only a few people who expressed second thoughts about this new miracle compound. One was nature writer Edwin Way Teale, who warned, "A spray as indiscriminate as DDT can upset the economy of nature as much as a revolution upsets social economy. Ninety percent of all insects are good, and if they are killed, things go out of kilter right away." Another was Carson, who wrote to Reader's Digest to propose an article about a series of tests on DDT being conducted not far from where she lived in Maryland. The magazine rejected the idea.

Silent Spring

Thirteen years later, in 1958, Carson's interest in writing about the dangers of DDT was rekindled when she received a letter from a friend in Massachusetts bemoaning the large bird kills that had occurred on Cape Cod as the result of DDT sprayings. The use of the pesticide had proliferated greatly since 1945, and Carson again tried, unsuccessfully, to interest a magazine in assigning her the story of its less desirable effects. By 1958, Carson was a best-selling author, and the fact that she could not obtain an assignment to write about DDT is indicative of how heretical and controversial her views on the subject must have seemed. Having already amassed a large quantity of research on the subject, however, Carson decided to go ahead and tackle the issue in a book.

Silent Spring took Carson four years to complete. It meticulously described how DDT entered the food chain and accumulated in the fatty tissues of animals, including human beings, and caused cancer and genetic damage. A single application on a crop, she wrote, killed insects for weeks and months-not only the targeted insects but countless more-and remained toxic in the environment even after it was diluted by rainwater. Carson concluded that DDT and other pesticides had irrevocably harmed animals and had contaminated the world's food supply. The book's most haunting and famous chapter, "A Fable for Tomorrow," depicted a nameless American town where all life-from fish to birds to apple blossoms to human children-had been "silenced" by the insidious effects of DDT.

First serialized in The New Yorker in June 1962, the book alarmed readers across America and, not surprisingly, brought a howl of indignation from the chemical industry. "If man were to faithfully follow the teachings of Miss Carson," complained an executive of the American Cyanamid Company, "we would return to the Dark Ages, and the insects and diseases and vermin would once again inherit the earth." Monsanto published and distributed 5,000 copies of a brochure parodying Silent Spring entitled "The Desolate Year," relating the devastation and inconvenience of a world where famine, disease, and insects ran amok because chemical pesticides had been banned. Some of the attacks were more personal, questioning Carson's integrity and even her sanity.

Vindication

Her careful preparation, however, had paid off. Anticipating the reaction of the chemical industry, she had compiled Silent Spring as one would a lawyer's brief, with no fewer than 55 pages of notes and a list of experts who had read and approved the manuscript. Many eminent scientists rose to her defense, and when President John F. Kennedy ordered the President's Science Advisory Committee to examine the issues the book raised, its report thoroughly vindicated both Silent Spring and its author. As a result, DDT came under much closer government supervision and was eventually banned. The public debate moved quickly from whether pesticides were dangerous to which ones were dangerous, and the burden of proof shifted from the opponents of unrestrained pesticide use to the manufacturers.

The most important legacy of Silent Spring, though, was a new public awareness that nature was vulnerable to human intervention. Carson had made a radical proposal: that, at times, technological progress is so fundamentally at odds with natural processes that it must be curtailed. Conservation had never raised much broad public interest, for few people really worried about the disappearance of wilderness. But the threats Carson had outlined-the contamination of the food chain, cancer, genetic damage, the deaths of entire species-were too frightening to ignore. For the first time, the need to regulate industry in order to protect the environment became widely accepted, and environmentalism was born.

Carson was well aware of the larger implications of her work. Appearing on a CBS documentary about Silent Spring shortly before her death from breast cancer in 1964, she remarked, "Man's attitude toward nature is today critically important simply because we have now acquired a fateful power to alter and destroy nature. But man is a part of nature, and his war against nature is inevitably a war against himself? [We are] challenged as mankind has never been challenged before to prove our maturity and our mastery, not of nature, but of ourselves."

One of the landmark books of the 20th century, Silent Spring' s message resonates loudly today, even several decades after its publication. And equally inspiring is the example of Rachel Carson herself. Against overwhelming difficulties and adversity, but motivated by her unabashed love of nature, she rose like a gladiator in its defense.

This NRDC.org story is available for online republication by news media outlets or nonprofits under these conditions: The writer(s) must be credited with a byline; you must note prominently that the story was originally published by NRDC.org and link to the original; the story cannot be edited (beyond simple things such as grammar); you can't resell the story in any form or grant republishing rights to other outlets; you can't republish our material wholesale or automatically-you need to select stories individually; you can't republish the photos or graphics on our site without specific permission; you should to let us know when you've used one of our stories.

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How a courageous woman took on the chemical industry and raised important questions about humankind's impact on nature.

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Rachel Louise Carson: the renowned writer, scientist, biologist, and ecologist

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We explore the life of scientist Rachel Carson, perhaps the finest and most important nature writer of the 20th Century.

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Evening star. [volume] (Washington, D.C.) 1854-1972, September 23, 1962, Page B-5, Image 31

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Evening star. [volume] (Washington, D.C.) 1854-1972, September 23, 1962, Page B-5, Image 31, brought to you by Library of Congress, Washington, DC, and the National Digital Newspaper Program.

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Search America's historic newspaper pages from 1770-1963 or use the U.S. Newspaper Directory to find information about American newspapers published between 1690-present. Chronicling America is sponsored jointly by the National Endowment for the Humanities external link and the Library of Congress. Learn more

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. SUNDAY. THB STAR MAOAZINX. WASHINGTON. D. C . OCTOBER 14. 1902
RACHEL CARSON is at peace with
her own environment The war of
survival between man and insect, a sub
ject of grave concern for this author and
biologist, seems a million miles away
(Torn the serenity of her Silver Spring
home.
Miss Carson lives in a spacious brick
house she built at 11701 Berwick road
with royalties from her writings.
Sitting in the soothing atmosphere
of a summer evening, as fireflies
bounced by the patio, one had to strug-
An Interview With Rachel Carson
gle to comprehend the ominous import
of Miss Carson's words. "We've got to
come to terms with our environment or
perish," she was saying. "I shudder to
think of some ftiture species viewing mu
seums filled with the bones of creatures
ourselves-for whom the environment
was no longer suitable. Future genera
tions won't believe that we actually con
taminated our own environment."
Miss Carson, 55, whose book "The
Sea Around Us," was a best seller that
was made into a movie, has a new book,
"Silent Spring," just off the presses.
"Silent Spring," which was serial
ized this summer in The New Yorker,
deals with civilization's exaggerated
chemical war on insects, a war that has
killed other wildlife and vegetation and
has developed worse insects through
Darwin's survival principle-by killing
off the natural enemies of the stronger
pests and by making the survivors im
mune to chemicals.
This situation has created the need
for a new war, Miss Carson said, her
eyes twinkling. "We must make war
against the increasing artificiality and
contamination of our environment
caused by using chemicals to control
organisms we don't want"
Our chief weapon for this war, Miss
Carson said, is research.
"If we put into research a fraction of
the money now spent on chemicals, we
would be able to find ways to control
these organisms so they would not dam
age the environment," she said.
"Real control doesn't depend on
what we do; it depends upon the built-in
controls in nature."
Miss Carson noted that, just as some
germs develop a resistance to anti
biotics, certain malaria-carrying mos
quitoes now are resistant to DDT. When
certain insecticidal sprays, such as
DDT, are introduced into the insects'
battle for survival of the fittest, tougher,
meaner-than-ever insects are created.
The cartoon of a giant insect hover
ing over a tiny helpless human "might
not be so far-fetched if we keep on spray-
ing with poisonous insecticides," Miss
Carson said.
Since most of her book was serial
ized in The New Yorker, Miss Carson
said, she had been getting letters from
gardeners and farmers wanting to know
what they need to do instead of spraying.
In most cases, there's little they
can do until more research is done, ex
cept to use extremely small quantities
of standard chemicals.
Miss Carson said the Agriculture
Department is doing "excellent work"
By JANET KOLTUN
in developing biological methods of
control. Biological methods find some
weakness in the history of an insect or
animal and turn that inherent weak
ness against the creature.
For instance, she said, one Agricul
ture Department scientist, Dr. Edward
Nipling, discovered how to control one
terrible pest, the screw-worm fly, by
sterilizing males and releasing them to
overwhelm normal males.
Another method of insect control,
still in the research stage, is microbial,
Miss Carson said. Japanese beetles, for
instance, have been controlled by re
leasing certain spores in their vicinity.
And another death-dealing bacteria has
been perfected for use against slugs.
Methods of radiation also are being
used to kill flies, she said.
But this touches another menace,
Miss Carson said, since radioactive
wastes also are contaminating our
world, including our rivers and oceans.
"All that radioactive waste taken
out and dumped in the sea is a contam
inating influence," she said. For a long
time, she explained, wastes were
dumped in inadequate containers.
"Some of the containers split before
they got to the bottom," she said.
Contending that much research
should be done before "idiot humans
release radioactive wastes into the
atmosphere," Miss Carson said:
"We should at least have discovered
how to keep radiation out of food or at
least how to take it out once it gets in."
Insecticides first became a concern
to Miss Carson when she was editor-in
chief at the Fish and Wildlife Service,
in the late 19405, "because of what hap
pened to wildlife."
Miss Carson said her next book
would concern discovering nature with
children, including a favorite nephew,
1 but that after four-and-a-half years on
"Silent Spring," she wanted a vacation.
"I wanted to write it before I got in
volved in "Silent Spring," she said.
"It's going to be a BIG book," says
her nephew.

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Chapter 1 | Rachel Carson | American Experience | PBS

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Abstract

General trends and strategies for novel pesticides are summarized. Global pesticide sales and pesticide discovery research are also briefly reviewed. At least 105 chemical pesticides have been launched during the past decade or are under development: 43 fungicides, 34 insecticides/acaricides, 6 nematicides, 21 herbicides, and 1 herbicide safener. Most of them are safe to humans and environmentally friendly. The most developed fungicides are SDHI (succinate dehydrogenase inhibitors), DMI (demethylation inhibitors), QoI (quinone outside inhibitors), and QiI (quinone inside inhibitors). Due to the development of resistance to fungicides with existing modes of action, many fungicides possessing various novel modes of action have been launched or are under development. The trend of insecticide development is changing from organophosphorus, carbamate, and synthetic pyrethroids to nicotinic and diamide insecticides. During the past decade, compounds possessing a variety of novel modes of action have also been launched or are under development. Flupyradifurone and flupyrimin, exhibiting extremely low honeybee toxicity, have been developed and subjected to practical use. Herbicides possessing varied modes of action, such as acetolactate synthase, p-hydroxyphenylpyruvate dioxygenase, protoporphyrinogen oxidase, and very-long-chain fatty acid elongase inhibition, have been developed, but no herbicides possessing a novel mode action have commercialized in nearly 30 years. It is of interest that cyclopyrimorate, which was recently launched, and tetflupyrolimet, which is under development, have novel modes action: homogentisate solanesyltransferase (HST) and dihydroorotate dehydrogenase (DHODH) inhibition, respectively. The development of useful acaricides and nematicides is also progressing. Some natural product origin pesticides are getting attention.

Keywords: novel pesticides, herbicide, fungicide, insecticide, acaricide, nematicide

Introduction

Since the practice of agriculture began about 10,000 years ago in the Fertile Crescent of Mesopotamia, mankind has battled pests and diseases that threaten the sustainable food supply. The first recorded use of pesticides is about 4500 years ago by Sumerians who used sulfur compounds to control insects and mites. The evolution of pesticides is classified into five single phases, namely, before 1000: early pest management; 1000-1850: use of plant, animal, or mineral derivatives; 1850-1940: use of inorganic products and industrial by-products; 1940-1970: use of synthetic organic compounds; 1970-present: use of lower-risk synthetic organic compounds.1) When organic chemistry was introduced to the pesticide science field after World War II, the door of industrial pesticide science was opened. In the past century, many pesticide companies have been founded in Europe and the USA, most of which were merged in the 21st century, and various kinds of pesticides have been launched throughout the world. The wave of pesticide science came to Japan, and Japanese-origin pesticides have been developed one after another from the late 20th to the early 21st century. Currently, the pesticide production ability in Japan ranks topmost in the world.

The development and manufacture of effective, safe to humans, and environmentally friendly pesticides have been a challenge to feed the growing population of our planet. The development of pesticides that pose a lower risk to natural enemies and useful organisms and are compatible with IPM (Integrated Pest Management) was also an important target. In March 2018, a book titled Trend in Pesticide Discovery Research-Development of Safer and Environmentally Friendly Pesticides,2) overviewing pesticide discovery research with insecticides, acaricides, nematicides, fungicides, herbicides, natural-origin pesticides, biopesticides, and others in the world during the past decade, was published by the CMC Publishing Co. In the book, which was edited by one of the authors of the current manuscript, 43 Japanese and Chinese pesticide scientists gave an overview of the trends in pesticide discovery research in their area of expertise from around 2009 to the end of 2017. Since significant progress has been made in pesticide discovery research after publication of the book, the contents of the pesticide discovery research, including the progress until early 2019, have been summarized as a series of commentary articles.3-8)

This manuscript is an attempt to summarize the overall trends in research, development, and commercialization of safer and environmentally friendly pesticides from around 2009 until early 2020 on the bases of the information on pesticide discovery research contained in the above book, the commentary articles, and the latest information thereafter.

1. General trends and strategies for novel pesticides

Since the appearance of synthetic organic pesticides, the development strategy for creating new pesticides has been as follows9): (1) development of pesticides that are effective at an extremely low dosage, (2) development of pesticides that are readily degradable and less residual in the environment, and (3) development of selective toxic agrochemicals. The first strategy resulted in a remarkable decrease in the active ingredient required for the control of pest insects, fungi, mites, nematodes, and weeds and eventually brought about a reduction in the load of pesticides to the environment. The second strategy realized the remarkable lowering of pesticide residue levels in crops and the environment. The third strategy to seek a compound that is effective in targeting only organisms such as insects, fungi, mites, nematodes, and weeds, but not toxic against non-target organisms such as humans and beneficial organisms, was a tool for finding safer and environmentally friendly pesticides. These development strategies have become increasingly prominent.

The amount of active ingredient applied per unit area in the 1930s-1950s was high, about 1 to 10 kg/ha for ingredients such as DNOC, thiuram, and DDT. Therefore, the environmental impact was relatively large. However, since then, many pesticides that exhibit efficacy in a smaller amount have been developed, and the application rate per unit area has significantly decreased. Currently, there are not a few pesticides showing efficacy at 10 g or less/ha. As a result, the environmental impact of pesticides has been significantly reduced.

2. Global pesticide sales and pesticide discovery research

2.1. Sales of pesticide companies involved in pesticide discovery research worldwide

Figure 1 shows the 2016 and 2017 sales turnover of major pesticide companies worldwide10,11) with acquisition and merger information. The company with the highest sales is Chem China, which acquired Syngenta, the sales turnover being $10,041 M in 2016. In second place was Bayer, but now ranks first in sales since it acquired Monsanto, followed by Corteva Agriscience (Dow AgroSciences and DuPont merged) and BASF. In fifth place is UPL, which recently acquired Arysta LifeScience. In ninth place is Sumitomo Chemical, a Japan-based pesticide company ($1,913 M). Sumitomo Chemical has recently acquired four South American subsidiaries, including a Brazilian subsidiary of Nufarm,12) so the sales ranking of Sumitomo Chemical is likely to become higher. Many Japanese pesticide companies, such as Kumiai Chemical, Nihon Nohyaku, Nissan Chemical, and Ishihara Sangyo Kaisha, are very active in pesticide discovery research even though the size of the company is relatively small. Their sales turnover is shown separately in the lower left part of the figure.11)

2.2. Trends in global agrochemical patent activity

It is important to analyze the number of patent applications by global pesticide companies and research institutes as an indicator of pesticide discovery activities. According to Phillips McDougall,13) the number of patent applications for active pesticide ingredients with a priority date between 2008 and 2016 was 5,857. Of those, China accounted for 40% at 2,358, followed by Germany at 1,117, Japan at 706, the USA at 516, Switzerland at 487, and the Republic of Korea at 230. This suggests that pesticide discovery studies are actively carried out in these countries.

Table 1 shows the number of patent applications by company for 2008-2016.13) Of the total 3,298, Bayer had 638 applications and Syngenta 465, followed by BASF, Sumitomo Chemical, Corteva Agriscience (Dow+DuPont), and several other Japanese companies. In a case of patent applications by public institutions such as universities and research institutions (total 2,529), the top 10 are from China, such as the Chinese Academy of Agricultural Sciences (122), Nankai University (113), Zhejiang University (95), the Chinese Agricultural University (82), and Nanjing Agricultural University (57). This suggests that pesticide discovery studies are actively conducted by public institutions in China.

2.3. General trends in novel pesticide discovery research

During the past decade, different kinds of chemical pesticides-fungicides, insecticides, nematicides, acaricides, and herbicides, as well as biopesticides-have been subjected to development. Chemical pesticides launched or under development during the past decade is total at least 105, and most of them are safe to humans and environmentally friendly: 43 fungicides, 34 insecticides/acaricides, 6 nematicides, 21 herbicides, and 1 herbicide safener. Though pesticide discovery studies based on genomic information or the structure-activity relationship and by chemical biology have been actively conducted during the past decade, almost no products have been developed for practical use.

3. Fungicides

3.1. General trends in development

The fungicides for which ISO common name attached after 2010 are classified according to their mode of action and shown in Table 2 . General trends in fungicide development are as follows.14) The first general trends in fungicide development are progress in the development of three major fungicides. The most common is SDHI (succinate dehydrogenase inhibitors) or those considered to be SDHI due to their chemical structure characteristics. SDHIs have become one of the largest groups of agricultural fungicides, as well as DMI (demethylation inhibitors) and inhibitors of the mitochondrial electron transport chain complex III, i.e., QoI (quinone outside inhibitors) and QiI (quinone inside inhibitors) (see Fig. 2 ). The SDHI acts on complex II of the mitochondrial electron transport chains, as shown in Fig. 2 . Although the number of developed SDHIs has become comparable to those of DMI and QoI, post-SDHI fungicides are now desired due to successive reports on fungal pathogen resistance to existing SDHIs. DMIs, sterol biosynthesis inhibitors of the cell membrane typified by a triazole fungicide, continue to play an important role in controlling plant diseases due to their broad spectrum, high therapeutic effect, and relatively slow development of resistance. Therefore, the development of a few, if not all, new DMI fungicides is in progress in response to the appearance of resistance to existing DMIs and the fact that many important DMIs are listed in the compounds suspected to have endocrine disrupting effects in Europe. As a QoI fungicide that acts at the quinone outside (Qo) site of the inner membrane of complex III, 10 compounds have been developed since 2010. As a QiI fungicide that acts at the quinone inside (Qi) site of the inner membrane of complex III, two compounds have been developed since 2010.

The second general trend is the development of fungicides with a novel mode of action and a unique chemical structure. Those with a completely new mode of action as agricultural fungicides and those with unique chemical structures are being developed.

Other trends are the development of novel plant defense activators and novel natural product origin fungicides.

3.2. Recently launched or under development

3.2.1. SDHI fungicides

Table 3 shows information on 17 SDHI fungicides that were developed after 201014,15) except for boscalid which was launched in 2003. Penthiopyrad (Affet® SC, Gaia® WDG) by Mitsui Chemicals Agro, isofetamid (Kenja®) by Ishihara Sangyo Kaisha, pyraziflumid (Parade®) by Nihon Nohyaku, and inpyrfluxam (Indiflin™) by Sumitomo Chemical have already been marketed. Pyrapropoyne is under development by Nissan Chemical.

Isofetamid was registered in December 2014 in Canada, in July 2015 in the USA, and in November 2017 in Japan. It has broad-spectrum antifungal activity against Ascomycota (such as Botrytis spp., Sclerotinia spp., Monilinia spp., and Venturia spp.) and Deuteromycota (such as Alternaria spp. and Mycovellosiella spp.) and is effective against existing SDHI-resistant pathogens.16,17)

Pyraziflumid acquired registration in Japan in 2018. It is a versatile fungicide applicable to a wide range of crops such as rice, horticulture products, and turf. It has a pyrazine carboxamide skeleton.18,19)

Inpyrfluxam exhibits high efficacy against major plant diseases in the European region, such as brown rust on wheat, net blotch on barley, and black scurf on potatoes.20)

Flubeneteram, which just obtained an ISO common name in early 2020,21) is an anilide fungicide and is considered to be an SDHI based on its chemical structure.

Among multinational agrochemical manufacturers, one company has multiple SDHI fungicides15) and is trying to separate the compounds by usage method and target crops in response to the characteristics of the compounds. As an example, Syngenta developed four SDHI fungicides. Isopyrazam (Reflect®) is for foliar application to control rust and net blotch of wheat. Sedaxane (Vibrance®) is a seed-treatment fungicide for wheat, beans, and potatoes. Benzovindiflupyr (Solatenol™) is a rust-control fungicide for soybeans. Pydiflumetofen (Adepidyn™) is for the control of powdery mildew and Alternaria disease of vegetables, fruit trees, etc., as well as wheat leaf blight and wheat scab.22)

Bayer launched bixafen (Aviator® Xpro™, Siltra® Xpro™, etc.), penflufen (EverGol® Prime), and fluopyram (Luna®). Isoflucypram, under development by Bayer, exhibits efficacy for the control of leaf spot diseases on a large range of crops.23)

3.2.2. Inhibitors of the mitochondrial electron transport chain complex III

A total of 12 compounds have been launched or are under development as inhibitors of the mitochondrial electron transport chain complex III since 2010,14) their chemical structures being shown in Figs. 3(a), 3(b), and 4 . Of them, 10 compounds are QoI fungicides.

Pyribencarb (K-I Chemical Research Institute and Kumiai Chemical) was registered in 2012 in Japan (Trade name: Fantasista® GWP, Fanbell® GWP). It is a novel benzyl carbamate-type fungicide against a wide range of plant pathogenic fungi, especially gray mold and stem rot.24) Though pyribencarb belongs to QoI group, it is active against strobilurin-resistant fungi.

Picoxystrobin (Acanto®, Syngenta) was discovered by Syngenta and transferred to DuPont in 2006. DuPont registered it in the USA in 2012. In Japan, Nihon Nohyaku marketed it in 2016 as a Major® Flowable.25) Picoxystrobin is a strobilurin fungicide (QoI inhibitor) effective against a wide range of diseases.

Mandestrobin (Sclea® flowable, Sumitomo Chemical), a strobilurin fungicide, was discovered by Shionogi & Co., Ltd., and commercially developed by Sumitomo Chemical. It is effective against sclerotinia rot, fruit tree scab, etc., with a low risk of phytotoxicity.26,27) It was launched in 2016 in Japan and is under commercial development in many countries.

Metyltetraprole (Pavecto®, Sumitomo Chemical) is a new fungicide with a unique tetrazolinone moiety that is effective against pathogens resistant to existing fungicides. It is highly effective against a wide range of fungal diseases, including important cereal diseases, such as wheat leaf blight. Sumitomo Chemical is promoting development jointly with BASF in the EU, aiming to launch after 2022.28) Metyltetraprole is highly effective against QoI-resistant strains of various pathogen species.29,30)

Six QoI fungicides with ISO common names are currently under development by Chinese companies: coumoxystrobin, enoxastrobin, flufenoxystrobin, triclopyricarb, and fenaminstrobin by SRICI and pyriminostrobin by Shenyang Sciencreat Chemicals (see structures in Fig. 3(b) ).14) It is unclear whether they aim to obtain registrations around the world, as well as what characteristics each QoI has and how to segregate each product in the market.

As QiI fungicides, two compounds are currently under development. Fenpicoxamid (Inatreq™, Meiji Seika Pharma, Dow; currently Corteva Agriscience), whose structure is shown in Fig. 4 , is a conversion product of UK-2A isolated from the culture broth of Streptomyces spp. by Ueki et al. at Osaka City University, and its action is inhibition of the mitochondrial electron transport system complex III. Meiji Seika Pharma introduced UK-2A from the university and subjected it to joint development with Dow after converting its structure into fenpicoxamid.31) It is currently under development as an innovative fungicide for controlling key diseases in cereals, such as Septoria tritici and rust. It shows no cross-resistance to existing cereal fungicides.31,32) Fenpicoxamid is a propesticide, since it is converted to UK-2A in crops.

Florylpicoxamid (Adavelt™, Corteva Agriscience) is a neopicolinamide fungicide under development and presumed to be a QiI, having the same mode of action as fenpicoxamid. Florylpicoxamid controls a wide range of pathogens including Septoria spp., powdery mildew, Botrytis spp., Anthracnose, Alternaria, scab, Monilinia, and others.33)

3.2.3. DMI fungicides

Currently, three DMIs are under development, and their structures are shown in Fig. 5 .14) Of these, mefentrifluconazole and pyrisoxazole should be noted. Mefentrifluconazole (Revysol®) is the first isopropanol azole discovered and developed by BASF. Its registration was approved in the EU in 2019. It is highly effective against key fungal diseases in both row and specialty crops, including cereals, corn, soybeans, rice, grapevines, fruits, vegetables, and turf.34) Pyrisoxazole, developed by SRICI, is a pyridine-type DMI that is effective against Botrytis cinerea and tomato leaf mold. The development status for this fungicide outside China is unknown.

3.2.4. Mode of action is novel or unknown

Eight fungicides with a novel or unknown mode of action and marketed or under development since 2010, is given based on the review by Fushikida14) and on other additional information. The chemical structures of these compounds are shown in Fig. 6 .

Flutianil (Gatten® EC, OAT Agrio Co.) was registered in 2013 in Japan.35) Flutianil is chemically characterized as a cyanomethylene thiazolidine. It exhibits therapeutic and preventive effects against powdery mildew at a low dosage.36) The mode of action of this compound has not yet been reported.

Fenpyrazamine (Prolectus®, Pixio® DF, Sumitomo Chemical) is a novel fungicide with an aminopyrazolinone structure that has shown high efficacy against gray mold, stem rot, and brown rot in field trials. The target enzyme of fenpyrazamine is the 3-keto reductase in the ergosterol biosynthetic pathway.37) Prolectus® was first launched in Italy in 2012, and Pixio® DF was launched in Japan in 2014.

Picarbutrazox (Pythilock®, Nae Fine®, Pisi Rock®, Nippon Soda) was registered in June 2017 in Japan.38) It belongs to the tetrazolyl oxime class, controlling oomycete diseases such as downy mildew and late blight. The mode of action of this compound is unknown, but it seems to have a new one, since the treatment of picarbutrazox causes swelling and hyperbranching of mycelia and inhibits zoospore formation, zoospore encystment, and cystospore germination.39)

Tebufloquin (Try® flowable, Meiji Seika Pharma) was registered in 2013 in Japan.14) It is used to control rice blast disease. The mode of action of this compound has not been clarified, but it is considered a respiratory inhibitor that acts on the mitochondrial electron transport system.

Pyriofenone (Property® flowable, Ishihara Sangyo Kaisha) is a novel fungicide with a benzoyl pyridine structure and was registered in 2013 in Japan. It is very effective against powdery mildew on wheat, cucumbers, strawberries, and eggplants. It is of interest that pyriofenone is effective against QoI- and DMI-resistant fungal plant pathogens. The mode of action of this compound was reported to be inhibition of the formation of appressoria and conidia and induction of morphological abnormality of the secondary appressorium and hyphae.40)

Oxathiapiprolin (Zorvec™, Orondis™, Corteva Agriscience) is a new class of piperidinyl thiazole isoxazoline fungicide.41) The US EPA approved it in 2015 for use against several fungal diseases, including downy mildew and late blight on crops such as vegetables, ornamentals, and turf. Its mode of action involves binding to the oxysterol-binding protein in Oomycetes.14,42) The practical spray concentration of this compound is about 20 ppm.

Tolprocarb (Sanblas®, Mitsui Chemicals Agro) is a rice blast fungicide registered in 2015 in Japan. Its mode of action was revealed to be inhibition of the polyketide synthase in the melanin biosynthesis pathway. In addition, tolprocarb induces systemic acquired resistance in Arabidopsis thaliana and rice. Owing to these double modes of action, tolprocarb can efficiently control not only rice blast but also bacterial diseases.43) Tolprocarb also provides long-term residual activity.

Quinofumelin (Mitsui Chemicals Agro) has new action characteristics. It effectively controls scabs, Botrytis cinerea, blast disease, and anthrax of fruits, vegetables, rape seeds, rice, etc. Mitsui Chemicals Agro signed a global license agreement with Bayer for its development and commercialization. They plan to apply for registration in 2020 in Japan and other countries.44,45)

3.2.5. Others

Four other fungicides, the structures of which are shown in Fig. 7 , are currently under development. Dichlobentiazox (Kumiai Chemical) is a novel fungicide that seems to be a plant defense activator created in the search for saccharin derivatives. It shows a stable effect against rice blast disease under various environmental conditions and treatment methods. It is also highly safe for rice seedlings with nursery box treatment. It is scheduled to launch in 2020.46)

Aminopyrifen (Agro-Kanesho) is a novel fungicide, and its synthesis and structure activity relationships were recently reported.47) It is reported that aminopyrifen inhibits the GWT-1 protein in glycosylphosphatidylinositol-anchor biosynthesis.48)

Dipymetitrone (Bayer) is a novel fungicide under development that is effective against Phytophthora rot, downy mildew, scab, early blight, and Botrytis cinerea.21,49) The mode of action is unknown.

The ISO common name of fluoxapiprolin (Bayer) was granted in October 2018.21) It is effective against Phytophthora rot and downy mildew. It seems to be in the same group of fungicides as oxathiapiprolin, under development by Corteva Agriscience.

4. Insecticides

4.1. General trends

In the history of insecticide development, trends have changed from organophosphates, carbamates, and synthetic pyrethroids to nicotinic and diamide insecticides.50) In recent years, compounds that are not classified into nicotinic and diamide insecticides and have or seem to have a variety of novel modes of action have been under development. This is useful in terms of resistance management.

Table 4 shows the major insecticides categorized into nicotinic, diamide, and other novel insecticides that were launched or under development after 2010. Four nicotinic insecticides, such as flupyrimin and triflumezopyrim, are on the market. As diamide insecticides, four compounds, such as cyantraniliprole and tetraniliprole, are on the market or under development. As other novel insecticides, nine insecticides, such as pyrifluquinazon, flometoquin, fluxametamide, broflanilide, and afidopyropen, will be mentioned below. The outline of each group of insecticides is also described below.

4.2. Trends in nicotinic insecticides

Nicotinic insecticides, which originate from nicotine, act on nicotinic acetylcholine receptors (nAChRs) and are effective against a wide range of pests at low doses; these made up about 23% of the global insecticide market in 2016. Nicotinic insecticides are classified into "first generation" (nicotine, anabasine), "second generation" (imidacloprid, thiacloprid, nitenpyram, clothianidin, acetamiprid, thiamethoxam, dinotefuran), and "third generation" (sulfoxaflor, flupyradifurone, flupyrimin, triflumezopyrim, dicloromezotiaz), which were launched or under development after 2010.50,51) Some nicotinic insecticides of the second generation have been regarded as toxic to some non-target organisms, especially honeybees, and the use of three agents is prohibited in the field in the EU.

Figure 8 shows the structure of nicotinic insecticides and their honeybee toxicity information.4) Due to the potential honeybee toxicity problem, the use of imidacloprid, clothianidin, and thiamethoxam was prohibited in the EU as a preventive measure in April 2013 and officially banned for use outdoors in 2018.

Regarding sulfoxaflor (Isoclast™), which is classified as sulfoximines, the US EPA banned its use in March 2016 due to the lack of honeybee toxicity data based on the outcome of a trial involving a beekeeper's organization (the EPA lost). However, it was re-registered in February 2017. Sulfoxaflor shows a stable effect against sucking pests, especially stink bugs and scales, and was registered in Japan in November 2017.

Flupyradifurone (Sivanto™), which is classified as butanolides, was registered in the USA and Japan in 2015. It is assumed to be harmless to honeybees, although like neonicotinoids, it binds to nAchRs. It was shown that flupyradifurone can reduce taste and appetitive learning performance in honeybees foraging for pollen and nectar, although only the highest concentration had significant effects.52)

Flupyrimin, which is classified as neonicotinoids, was registered in Japan in 2019 (trade name: Lydia Granules, Emilia Flowable) and exhibits remarkable biological properties featuring outstanding potency to neonicotinoid-insensitive rice insect pests and superior safety toward pollinators. Intriguingly, flupyrimin acts on the insect nAChRs as an antagonist via a recognition manner different from those of the other nicotinic insecticides.53)

Triflumezopyrim (Pyraxalt™) and dicloromezotiaz belong to the novel class of mesoionic insecticides and have already been commercialized.54) Triflumezopyrim provides outstanding control of hoppers, including the brown planthopper, which is already displaying resistance to neonicotinoids such as imidacloprid.55) Dicloromezotiaz shows excellent efficacy against a broad range of lepidopteran pests. It binds to the orthosteric site of the nicotinic acetylcholine receptor but acts primarily via inhibition of the binding site and leads to lethargic poisoning among different insect species.56)

Though the IRAC classification is not described, research and development of nicotinic insecticides by Chinese institutions are ongoing, and cycloxaprid, paichongding, guadipyr, and cycloxylidin (see structures in Fig. 9 ) have been developed as insecticides in China.51) The status of the development of these nicotinic insecticides outside China is unknown. Cycloxaprid, developed by East China University of Science and Technology, shows outstanding activity against a variety of homopteran and lepidopteran pests and lacks cross-resistance in comparison with traditional neonicotinoids.57) It acts on insect nAChRs but has different binding sites than that of imidacloprid.

Table 5 summarizes the honeybee toxicity data for these nicotinic insecticides.4) Oral and contact toxicities to honeybees are generally low or relatively low for the nicotinic insecticides except for the three compounds banned in the EU. Among them, the contact toxicity of thiacloprid is about 1/800 that of imidacloprid. The recently marketed flupyradifurone and flupyrimin ( Fig. 8 ) have even lower honeybee toxicities. Selective toxic insecticides were developed using honeybee toxicity as an index.

4.3. Trends in diamide insecticides

Table 6 shows the development history of diamide insecticides.4) Nihon Nohyaku developed flubendiamide and obtained registration in 2007, and this was followed by DuPont's chlorantraniliprole. After 2010, cyantraniliprole, cyclaniliprole, tetraniliprole, cyhalodiamide, and tetrachlorantraniliprole followed. Chlorantraniliprole and cyantraniliprole, which were originally developed by DuPont, were recently transferred to FMC. These compounds have a novel mode of action, acting on ryanodine receptors, and because of their excellent control performance, particularly with lepidopteran pests, they can be used in a wide range of crop-protection situations. In 2016, three diamide insecticides, flubendiamide, chlorantraniliprole, and cyantraniliprole, together accounted for 11.5% of the $16.46 billion global insecticide market.

Cyclaniliprole (Teppan®), which was registered by Ishihara Sangyo Kaisha in Japan in 2017, is highly effective against lepidopteran pests as well as hemipteran pests such as thrips, whitefly, and tea green leafhopper.58,59)

4.4. Trends in novel insecticides other than nicotinic and diamide insecticides

An overview of the 11 insecticides other than nicotinic and diamide insecticides that were launched or are under development after 2010 is described based on Suwa and Nakano's review50) and on other recent information. Figure 10 shows the chemical structures of these 11 insecticides and their related compounds.

Pyrifluquinazon (Colt®, Nihon Nohyaku) is an insect behavior control agent (to halt insect feeding so that they starve) for tea, vegetables, and fruit trees that was registered in Japan in 2010. It also shows a good effect on Bemisia tabaci (tobacco whitefly), biotype Q.50,61)

Flometoquin (Finesave®, Nippon Kayaku and Meiji Seika Pharma), an insecticide with a quinoline skeleton, was registered in Japan in March 2018.62) It is effective to control Lepidoptera, Diptera, Hemiptera, and mites. Applicable crops are fruit trees, vegetables, etc. It inhibits the electron transport system.

Fluxametamide (Gracia®, Nissan Chemical), an isoxazoline compound, was discovered and has been developed, being registered in January 2019 in Japan. The site of action is GABA: γ-aminobutyric acid (GABA Cl −, Glu Cl −channel inhibitor). The characteristics of fluxametamide include effectiveness against a very broad spectrum of important pests (Lepidoptera, Thysanoptera, Diptera, Acari, Coleoptera, and some Hemiptera). There is little influence on the bee-visiting insects.63,64)

Broflanilide (Vedira™, Tenebenal™, Mitsui Chemicals Agro), currently being jointly developed with BASF, has a unique chemical structure characterized as a meta-diamide and exhibits high activity against various pests, including lepidopteran, coleopteran, and thysanopteran pests.65,66) Broflanilide received the first registration worldwide in Australia in January 2020. Broflanilide is metabolized to desmethyl-broflanilide, and it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl-broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil.

Benzpyrimoxan (Orchestra® flowable, Nihon Nohyaku) is currently under development. It seems to be a next-generation planthopper and green rice leafhopper control insecticide.50) Benzpyrimoxan is highly active, specifically against the nymphal stages, and could act on nymphal molting as a kind of insect growth regulator (IGR). Its insecticidal activity against nymphs is much superior to that against other stages, with a unique symptom that is different from ones caused by other existing IGR products.67)

Spiropidion (Syngenta) is a new tetramic acid family member (IRAC MoA group 23) insecticide and acaricide and is currently under development by Syngenta.70,71) It is regarded as an inhibitor of acetyl CoA carboxylase, disrupting fatty acid biosynthesis, and is presumed to show excellent activity against aphids, whiteflies, thrips, diamondback moths, and mites in vegetables and specialty crops. It has a favorable toxicological and environmental profile and, owing to its safety to pollinators and other non-target organisms, it is perfectly suitable for IPM practices.

Afidopyropen (Inscalis®, Meiji Seika Pharma) is a structurally modified compound of pyripyropene A,72) an antibiotic obtained from the culture of Aspergillus fumigatus through collaboration between the Kitasato Institute, Meiji Seika Pharma, and BASF.72,73) The circled parts in the chemical structure of afidopyropen in Fig. 10 are the structure conversion sites. The joint development company BASF applied for registration in the USA and Canada. Afidopyropen controls aphids, whiteflies, scales, and leafhoppers, being effective against pests that have acquired resistance to existing insecticides. It is presumed that afidopyropen acts on the chordotonal organ, an insect-specific hearing organ. Details of the development of this insecticide are described in Oyama's review.74)

Isocycloseram (Syngenta) is a member of the isoxazoline class of insecticides.75) The ISO common name was given in June 2018. It is in the same family as fluxametamide from Nissan Chemical. Isocycloseram acts as a noncompetitive antagonist of the invertebrate GABA receptor.

Dimpropyridaz (BASF) is a new insecticide, the ISO common name being given in December 2018.21) It is a pyrazole carboxamide insecticide that has a pyridin-3-yl group, as in tyclopyrazoflor.50) Dimpropyridaz is effective against aphids.

5. Acaricides

5.1. General trends in acaricide development

Although the types of acaricides seem to be numerous at first glance, the key acaricides have changed over time due to the development of resistance. Though there were only a limited number of modes of action for acaricides until the 1990s, acaricides with various modes of action have been developed since the 2000s.76) The acaricides developed after 2000 are classified as "Inhibitors of the mitochondrial electron transport chain complex II," "Acetyl CoA carboxylase inhibitors," and "Acaricides possessing a novel mode of action or unknown mode of action."

5.2. Trends in the development of inhibitors of the mitochondrial electron transport chain complex II

This class of acaricides started with a novel benzoyl acetonitrile acaricide, cyflumetofen (Danisaraba®), which was discovered by Otsuka Chemical (currently OAT Agrio) and registered in 2007 in Japan.76) Then cyenopyrafen (Starmite®, registered in 2008 by Nissan Chemical) and pyflubumide, a carboxyanilide acaricide (Dani-Kong®, registered in 2017 by Nihon Nohyaku), were developed and marketed.76) The chemical structure of the three acaricides is shown in Fig. 11 . All three acaricides are effective at all stages of spider mite development as inhibitors of the mitochondrial electron transport chain complex II. It is of interest that pyflubumide has the same mode of action as the other two acaricides, but the site of action is different, and cross-resistance is avoided.77) Cyetpyrafen (Sinochem), the ISO common name being given in 2020,21) is presumed to be an inhibitor of the mitochondrial electron transport chain complex II based on the similarity in chemical structure to cyenopyrafen.

5.3. Trends in the development of acetyl CoA carboxylase
inhibitors

Three acetyl CoA carboxylase inhibitors have been developed and marketed since 2003.76) These acaricides act by inhibiting lipid biosynthesis. There are two tetronic acid classes, spirodiclofen (Daniemon®, registered in 2003 in Japan) and spiromesifen (Danigetter®, registered in 2007 in Japan), and a tetramic acid class, spirotetramat (Movento®, Ultor®, registered in 2012 in Japan). The above three acaricides were developed by Bayer (see the chemical structure in Fig. 11 ). The general characteristics of biological activity are the same for the three acaricides, and they are effective not only for spider mites but also for rust mites. Characteristics of above three acaricides are as follows.76) Spirodiclofen is effective only against mites and has no systemic activity. Spiromesifen shows activity against both mites and whiteflies. It also has leaf penetration activity. Spirotetramat is effective not only for mites but also for sucking pests. It has phloem migration activity, and irrigation treatment into the soil is possible.76)

In addition to the above three acaricides, spiropidion, which was mentioned in the section on novel insecticides, exhibits acaricidal activity.70)

5.4. Trends in the development of acaricides possessing a novel or unknown mode of action

Three acaricides with a novel or unknown mode of action have been developed since 2010. Fluxametamide (Gracia®, Nissan Chemical) is an insecticide and acaricide. See item 4.4, "Trends in novel insecticides other than nicotinic and diamide insecticides".

Acyonapyr (NA-89, Danyote®, Nippon Soda) has a characteristic azabicyclo ring in its structure76,78) and was registered in March 2019 in Japan. It is reported that acynonapyr acts on inhibitory glutamate receptors and disrupts neurotransmission.78) It has a selective effect on spider mites of Tetranychus and Panonychus. The practical concentration of acynonapyr is 100-67 ppm, and its application is currently expanding into fruit, tea, vegetables, and flowering fields.

Flupentiofenox (Kumiai Chemical) is a new acaricide, the ISO common name being given in 2020.21) Other information, including the mode of action, is not available.

5.5. Trends in the development of non-chemically synthesized acaricides

Two non-chemically synthesized acaricides have been developed since 2010. Formulated oil (safflower oil and cottonseed oil 97%, RM1963K, Suffoil® emulsion) was registered in 2015 in Japan, jointly developed by OAT Agrio and RIKEN. It can be used at a relatively high dilution ratio of 300 to 500 times (compared to machine oil, etc.). The mode of action against spider mites is suffocation by spiracle blockage of adults and larva, but at the same time, it inhibits larval escape behavior in eggs during hatching, thus exhibiting an egg-killing effect.5,79)

Polyglycerin fatty acid ester 82% (Fumon®, Nippon Kayaku) is a food additive and was registered in 2016 in Japan, having insecticidal, fungicidal, and acaricidal activities. Its only mode of action is spiracle blockage, and it can be sprayed at a high dilution (×1,000), so the risk of phytotoxicity is relatively low.76)

6. Nematicide development

6.1. General trends

The methods of controlling plant-parasitic nematodes are largely divided into fumigant (gas) treatments and non-fumigant (contact agent) treatments. Most nematicides exhibits control effect by entering the nematode body through the surface phospholipid membrane. Methyl bromide, a typical fumigant, had a wide range of effects and was widely used around the world because of its low cost. However, the use of methyl bromide had been abolished in developed countries by 2005 due to fears of ozone depletion and groundwater pollution at the Montreal Protocol meeting in 1995.80) In recent years, pesticide manufacturers have been actively developing safer non-fumigants.

6.2. Trends in development

The nematicides launched or under development after 2010 are shown in Fig. 12 with their chemical structures.80) Fluopyram (Bayer and Nihon Nohyaku) was developed and marketed as an SDHI fungicide by Bayer, but it has been reported by Nihon Nohyaku that it also acts as a nematicide. Bayer marketed it as Velum™ granules and Verango®,81) Nihon Nohyaku as Nemaclean® granules (August 2017 in Japan).82) These are the first nematicides acting via complex II inhibition, thus selectively inhibiting the nematode's generation of cellular energy. The nematicide exhibits a high control effect on the root-knot nematode, root-lesion nematode, cyst nematode, and potato rot nematode. Residual activity is also very high.

Tioxazafen (NemaStrike™, Monsant (currently Bayer)) is a seed-treatment nematicide developed by Monsanto to provide consistent broad-spectrum control of nematodes in corn, soy, and cotton.83) Its structure has a disubstituted oxadiazole skeleton, representing a new class of nematicides. Tioxazafen obtained EPA registration in May 2017. Its use started in 2018 in 45 states in the USA. It has a broad spectrum against parasitic nematodes of corn, soybeans, and cotton. It stays in the roots of the crop for up to 75 days during crop growth.80)

Fluazaindolizine (Reklemel™ active, Salibro®, Corteva Agriscience) is a new, highly effective, and selective product for the control of plant parasitic nematodes, and it is expected to be registered in 2020.80,84) It has an excellent effect on the root-knot nematode and root-lesion nematode. Specificity for nematodes coupled with the absence of activity against the target sites of commercial nematicides suggests that fluazaindolizine has a novel mode of action.

Cyclobutrifluram (Syngenta), the ISO common name being given in 2020,21) is presumed to be an inhibitor of the mitochondrial electron transport chain complex II based on its similarity in chemical structure to fluopyram.

Nemguard (NEMguard®, Ecospray) is a non-chemically synthesized nematicide. Nemguard is a registered soil-applied nematicide based on garlic extract. It contains biologically active ingredients such as allicin and polysulfides derived from garlic concentrate. In addition to nematicidal and insecticidal properties, the active ingredient also has fungicidal properties.86) In Italy, NEMguard WF has been registered for use on a range of crops, including carrots, potatoes, and tomatoes.

7. Herbicides

7.1. General trends

Since the 1940s, a large number of herbicides with different modes of action have been developed and provided for commerce use. Figure 13 shows the history of the discovery of herbicides with different modes of action, which can be roughly divided into pre-1980, the 1980s, the 1990s, and after 2018. The history of herbicide development by age group is described below based on the review by Tamai et al. 87) and the latest information thereafter.

7.2. Research on the mode of action of old-fashioned herbicides

7.2.1. Before 1980⁸⁷⁾

The discovery of the auxin action of 2,4-D (2,4-dichlorophenoxyacetic acid), whose basic chemical structure is phenoxyacetic acid, in 1942 led to the discovery of a selective herbicidal effect on broadleaf weeds in 1944. From 1956 to 1975, the mode of action of urea, triazine, and triazinone photosynthesis inhibitors was elucidated. In the 1970s, the mode of action of auxin transport inhibitors (naptalam), cell wall synthesis inhibitors (dichlobenil), microtubule polymerization inhibitors (trifluralin), and dihydropteroate (an intermediate in folate biosynthesis) synthesis inhibitors (asulam) was revealed.

7.2.2. From the 1980s to the 2000s⁸⁷⁾

In 1980, it was revealed that the action point of pyridazine herbicides on the carotenoid biosynthesis pathway was phytoene desaturase (PDS). From 1982 to 1986, the site of action of phosphinothricin, the active form of glufosinate and bialaphos, was determined to be glutamine synthase (GS). From 1986 to 1989, it was clarified that the action point of diphenyl ether and phthalimide herbicides on the porphyrin biosynthetic pathway was protoporphyrinogen IX oxidase (PPO). In 1984, it was found that the action point of sulfonylurea herbicides and imidazolinone herbicides on the branched-chain amino acid synthesis pathway is acetolactate synthase (ALS), and the action point of glyphosate on the aromatic amino acid biosynthesis pathway is 5-enolpyruvylshikimate phosphate synthase (EPSPS). From 1992 to 1993, it was clarified that the action point of triketone herbicide, represented by sulcotrione, was 4-hydroxyphenylpyruvate dioxygenase (HPPD). A long-term study from 1993 to 2000 clarified that the action point of chloroacetamide herbicide, which had not been elucidated for many years, is the very-long-chain fatty acid elongase (VLCFAE). Since 2000, VLCFAE-inhibiting herbicides have been developed in addition to ACCase-, ALS-, HPPD-, and PPO-inhibiting herbicides.

7.2.3. After 2018

There were no reports on herbicides with a novel mode of action for approximately 30 years after the launch of clomazone (DXP inhibitor in the MEP pathway) in the late 1980s until 2017.87) However, three herbicides possessing new modes of action have recently appeared. First, it was clarified that the site of action of the herbicide cinmethylin, whose registration has expired (in Japan), is fatty acid thioesterase (FAT).88) The second herbicide is cyclopyrimorate. It has been reported that the site of action of this new herbicide, discovered by Mitsui Chemicals Agro and registered in Japan in September 2019, is the homogentisate solanesyltransferase (HST).89) The third one is a new herbicide, tetflupyrolimet, discovered by FMC. It was recently reported that tetflupyrolimet interferes with de novo pyrimidine biosynthesis via the inhibition of dihydroorotate dehydrogenase (DHODH).90)

7.3. Herbicides developed after 2008

The herbicides launched or under development after 2008 will be described based on the review by Tamai et al. 87) summarizing the herbicide discovery studies up to 2017 and on the latest information as of January 2020. Since ACCase-, PDS-, and photosynthesis inhibitors have not been developed during this period, the description of these herbicides has been omitted.

7.3.1. ALS inhibitors

ALS-inhibiting herbicides include sulfonylureas, triazolinones, triazolopyrimidines, pyrimidinylsalicylic acids, imidazolinones, and sulfonanilides. The number of ALS inhibitors being developed has been decreasing due to the problem of weed resistance to ALS inhibitors, and little discovery research has been conducted recently.87)

Table 7 shows the chemical structures, common names, company name, group names, registered year, target crops, and dosages of ALS inhibitors. Recently developed sulfonylurea ALS inhibitors include propyrisulfuron (Zeta-One®) from Sumitomo Chemical91) and metazosulfuron (Altair®) from Nissan Chemical.92) Both herbicides have been developed for paddy rice and are characterized by their effectiveness against broadleaf weeds and Cyperaceous weeds, as well as against barnyard grass, which is difficult to control with conventional sulfonylurea herbicides.

The other two are pyrimisulfan (Best Partner®) and triafamone, which are sulfonanilides. Pyrimisulfan, developed by Kumiai Chemical, has provided outstanding efficacy against major weeds of Japanese paddy fields, such as Echinochloa spp., Schoenoplectus juncoides, Monochoria vaginalis, and Lindernia spp. Pyrimisulfan is the first one-shot herbicide for rice containing only one active ingredient, with an original formulation technology.93) In addition, it can control other troublesome weeds, including Sagittaria trifolia, Scirpus nipponicus, Bolboschoenus maritimus, Eleocharis kuroguwai, and sulfonylurea-resistant weeds, which have presented serious problems in recent years.

Triafamone (Council™ Complete (triafamone+tefuryltrione), etc.), developed by Bayer, is an herbicide for paddy rice and is highly effective against grass weeds, such as barnyard grass, as well as Cyperaceous weeds.94)

7.3.2. HPPD inhibitors

HPPD-inhibiting herbicides represent the most actively researched field, and many are being developed. They include triketones, pyrazoles, isoxazoles, and other bicyclo ring-type compounds. In addition, Bayer published a patent in 2011 for an HPPD inhibitor characterized by an amide structure. Syngenta published a patent in 2013 for an HPPD inhibitor characterized by a pyridazinone ring.87)

Table 8 shows information on various HPPD inhibitors. The triketone herbicides include tefuryltrione (Mighty-One®), fenquinotrione (Effeeda®), and lancotrione-sodium (Promise®1 kg GR), launched in 2010, 2018, and 2019, respectively. Tefuryltrione, developed by Bayer, is effective against sulfonylurea-tolerant weeds as well as annual and perennial weeds belonging to the Cyperus microiria Steud family.95) Fenquinotrione, developed by Kumiai Chemical, shows excellent control against pre/post-emergence ALS-resistant broadleaf weeds under flooded conditions.96,97) It shows high safety to high-yield rice varieties for feed equal to or better than rice varieties for food. Lancotrione-sodium, registered in Japan in 2019 by Ishihara Sangyo Kaisha, is for paddy rice.7)

Bicyclopyrone, a bicyclo ring-type HPPD inhibitor, is an upland herbicide developed by Syngenta. It shows a broad herbicidal spectrum against grass weeds and broadleaf weeds before and after emergence.87)

Tolpyralate (Brucia® flowable), a pyrazole-type HPPD inhibitor, is a foliar spray herbicide for corn developed by Ishihara Sangyo Kaisha. It shows a high level of activity against a wide range of unwanted weeds, not only broadleaf weeds but also grasses.98)

7.3.3. PPO inhibitors

The PPO-inhibiting herbicides inhibit protoporphyrinogen-IX oxidase (PPO), which catalyzes the oxidation of protoporphyrinogen to protoporphyrin in the process of synthesizing the porphyrin ring. Inhibition of this enzyme ultimately results in pigment degradation and leaf necrosis, causing the plant to die. In recent years, the number of patent applications related to PPO-inhibiting herbicides has been declining.

Table 9 shows information on three PPO-inhibiting herbicides, tiafenacil (Dongbu Hannong Chemical), trifludimoxazin (BASF), and cyclopyranil (Kyoyu Agri), that have been in development since 2008.87) Trifludimoxazin (Tirexor™), currently under development by BASF, is a low-use-rate herbicide, from 12 to 50 g a.i./ha, that provides control of difficult-to-control weeds such as palmer amaranth and Kochia.99) It was designed to be active against existing PPO-resistant weeds, resulting in the broad-spectrum pre- and post-emergence herbicide.100)

7.3.4. VLCFAE inhibitors

The VLCFAE-inhibiting herbicides had been primarily chloroacetamides and oxyacetamides, but various skeletons have been identified since then. Very few patents for VLCFAE inhibitors have been published since 2008, and their skeletons are based on pyroxasulfone.

Table 10 shows information on four VLCFAE-inhibiting herbicides. Pyroxasulfone (Kumiai Chemical), ipfencarbazone (Hokko Chemical), and fenoxasulfone (Kumiai Chemical) have been in development since 2008. The fourth compound, dimesulfazet, just obtained an ISO common name in early 2020.21)

Pyroxasulfone (Axeev®, Zidua®) is an herbicide for upland crops such as wheat, soybeans, and corn. It shows high efficacy against hardly controllable gramineous weeds such as Johnson grass and Urochloa platyphylla and is also highly effective against weeds that have acquired resistance to glyphosate, ALS inhibitors, ACCase inhibitors, and dinitroaniline herbicides.87,101)

Ipfencarbazone (Winner®, Fighter®) is a triazolinone-based herbicide developed for paddy rice and exhibits high herbicidal activity against Echinochloa spp. from pre-emergence to the three-leaf stage while being safe for transplanted rice at a dosage of 250 g a.i./ha.102,103) It has excellent effect persistence and has a residual effect for about 70 days against barnyard grass.

Fenoxasulfone displays excellent herbicidal activity against Echinochloa spp. and other annual weeds at 150-200 g a.i./ha with long residual activity.104) Fenoxasulfone was registered in Japan in 2014, and various products containing fenoxasulfone have been launched.

Dimesulfazet (Nissan Chemical), which belongs to trifluoromethansulfonanilides, is presumed to be a VLCFAE inhibitor, since trifluoromethansulfonanilides such as mefluidide and perfluidone have been reported to inhibit a very-long-chain fatty acid synthesis.105)

7.3.5. Auxin-like herbicides and herbicide safener

Auxin-like herbicides include phenoxy carboxylic acids, benzoic acids, pyridine/pyrimidine carboxylic acids, and quinoline carboxylic acids. In recent years, mainly pyridine/pyrimidine compounds have been subjected to development.87)

Table 11 shows information on two auxin-like herbicides, halauxifen-methyl and florpyrauxifen-benzyl. Halauxifen-methyl (Arylex™), developed by Dow (Corteva Agriscience), is a pyridine-type auxin-like herbicide and is highly effective on major broadleaf weeds such as pigweed, henbit, corn poppy, flixweed, and chickweed at an extremely low dosage of 5-10 g/ha, with utility in multiple crops, the primary one being winter wheat.106) It is effective in managing weed biotypes resistant to other modes of actin such as ALS-inhibitor herbicides, glyphosate, and triazine herbicides. It has been shown that the activity (sensitivity to horseweed) of halauxifen-methyl is different from that of 2,4-D and dicamba,107) which are typical auxin-like herbicides.

Florpyrauxifen-benzyl (Rinskor™), developed by Corteva Agriscience, is also a pyridine-type auxin-like herbicide. It was unconditionally registered in the USA in 2017 and obtained approval in the EU in 2019. It is highly effective at postemergence control of grasses, sedges, and broadleaf weeds in rice crops. It is also being evaluated for use in other crops, including corn. In a greenhouse experiment, florpyrauxifen-benzyl at 30 g a.i./ha provided ≧75% control of many weed species, such as broadleaf signalgrass, barnyardgrass, Amazon sprangletop, and large crabgrass.108)

As an herbicide safener, only one compound, metcamifen, can be mentioned. Metcamifen prevented an herbicide, clodinafop-propargyl, from damaging rice seedlings, and this was associated with the enhanced detoxication of the herbicide.109)

7.3.6. Herbicide with a novel mode of action

As already mentioned, since 2018, and for the first time in 30 years, three herbicides possessing new modes of action have appeared. Table 12 shows information on three herbicides possessing a novel mode of action. Cyclopyrimorate (Cyra®), developed by Mitsui Chemicals Agro and launched in 2019 in Japan, is a rice herbicide.89,110) It shows a broad herbicidal spectrum against Cyperaceae weeds and broadleaf weeds. It is also highly effective against weeds that have acquired resistance to ALS inhibitors. Further, it can be applied simultaneously to rice planting and direct sowing cultivation in paddy fields. The site of action of cyclopyrimorate is HTS (homogentisate solanesyltransferase), a downstream enzyme of HPPD. In in vitro assays, HTS was inhibited strongly by DMC (a metabolite of cyclopyrimorate, des-morpholinocarbonyl cyclopyrimorate) and weakly by cyclopyrimorate. Although it has already been reported that HST inhibitors have herbicidal activity, cyclopyrimorate is the first commercial herbicide having this mode of action.

Tetflupyrolimet is a novel herbicide class of aryl pyrrolidinone anilides under development by FMC, the ISO common name being given in January 2019. It interferes with de novo pyrimidine biosynthesis via the inhibition of dihydroorotate dehydrogenase (DHODH).90) It has demonstrated a high level of activity against grasses.

Cinmethylin is an herbicide whose registration has expired, at least in Japan. It has recently been revealed by BASF scientists that cinmethylin binds to fatty acid thioesterase (FTA), a new herbicidal site of action, and inhibits plant fatty acid biosynthesis.88) BASF has recently developed cinmethylin (Luximax, trade name: Luximo TM)) as an herbicide to control key grasses in cereals. It demonstrates excellent efficacy against blackgrass and ryegrass, including resistant biotypes, while maintaining crop selectivity.111) Australia granted the world's first approval to Luximo™ in 2019.112)

8. Concluding remarks

During the past decade, a wide variety of useful chemical pesticides that are safe to humans and environmentally friendly have been subjected to development. In the field of insecticides, acaricides, nematicides, and fungicides, new chemicals that have or are likely to have a novel mode of action and unique chemical structure have been continuously developed. This is extremely important in avoiding the development of pesticide resistance and enabling sustainable agricultural production. It is of interest that in the herbicide field, for the first time in 30 years, herbicides possessing a novel mode of action have appeared. This is significant for dealing with herbicide-tolerant weeds that have recently become a problem.

Though several new chemical pesticides originating from China (universities and companies) during the past decade are described in the present manuscript, this may not cover all new compounds from China. China's dissemination of information (outside the country) on new pesticides seems insufficient, and some new compounds have been developed mainly for domestic use.

Chemical pesticides developed over the past decade have played an important role in crop protection and are expected to play an important role in the future. However, it is true that in recent years, the trend of global pesticide development has been gradually shifting from chemical pesticides to biological pesticides, GM crops, seeds, RNAi pesticides, and abiotic stress control agents. Of those, biopesticides are gaining popularity as lower-environmental-impact alternatives to conventional synthetic pesticides. The research and advisory firm Lux Research in Boston, MA, USA, has made an interesting and bold prediction concerning the relationship between chemical pesticides and biopesticides. As shown in Fig. 14 , they predict that biopesticides will equal synthetic (chemical) pesticides in terms of market size by the late 2040s or early 2050s.113) It will be necessary to closely monitor the future trends of chemical pesticides.

Notes

To whom correspondence should be addressed. E-mail: noriumetsu-agrisci@oneself.jp

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Articles from Journal of Pesticide Science are provided here courtesy of Pesticide Science Society of Japan

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Development of novel pesticides in the 21st century

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General trends and strategies for novel pesticides are summarized. Global pesticide sales and pesticide discovery research are also briefly reviewed. At least 105 chemical pesticides have been launched during the past decade or are under development: ...

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DDT - A Brief History and Status | US EPA

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DDT was the first of the modern synthetic insecticides, developed in the 1940s. It helped control diseases such as typhus and malaria. Enviromental concerns led to its cancellation in the 1970s. It still has limited indoor use in Africa to prevent malaria.

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Pesticides - DDT - Rachel Carson - Silent Spring

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Modern pest management and control is an increasingly diverse science with thousands of different management strategies. Synthetic chemical pesticides, which were first deployed during the World War II era, are a relatively new development in an epic battle against pests and parasites. Prior to the development of synthetic pesticides, there was a slow, perpetual battle of simple tools and natural chemicals against the incessant onslaught of pests. More recently, pest control efforts have evolved into management strategies.

Chemical pest control methods encompass a large range of strategies from companion planting to chemical sterilization agents. The most common forms of chemical pest controls are pesticides, which are chemical or biological agents designed to deter, discourage, incapacitate, or kill a pest. Early pesticides included the use of botanicals and simple elements or compounds. Early Romans, for example, discovered that crushed olive pits could produce an oil called Amurea that was capable of killing pests. Subsequent scientific and cultural development led to the discovery and utilization of additional pesticide agents.

The heavy metal compounds were probably first employed as pesticides because of their high toxicity. Arsenic compounds (particularly Arsenic (III) oxides) were found to be highly toxic to insects, bacteria and fungi. Arsenic (III) oxides, which combine rapidly with thiols found in biologically important molecules such as cysteine and coenzyme A, interrupt enzymatic activities that include ATP production. Arsenic compounds are still used today in wood treatment and preservative processes as well as some arsenate pesticides. Mercury compounds (primarily organic mercury compounds) also have a high affinity for thiols, similar to arsenic compounds, and can disrupt biological and enzymatic processes. Meanwhile, lead compounds act as a calcium analog and cause incomplete heme synthesis, which leads to anemia.

The benefit of these inorganic pesticides, at the time, was that they lasted a long time and were not easily degraded. Unfortunately, they often leached into the ecosystem, wreaking havoc on local wildlife and posing a health threat to its human inhabitants.

Pest Control from the Middle Ages to the Victorian Era

In the span from the Middle Ages to the Victorian era, science moved from the realm of religion and magic to practical study. The disciplines of chemistry and biology were embraced, opening up studies into chemical compounds, reactions, and chemical synthesis. Pest control methods definitely benefited from this pursuit of knowledge. Older methods of pest control were still in use (removal, barriers, botanicals, and elemental salts) but the mechanisms behind their efficacy were still being discovered.

The 19th century marked the dawn of manufactured chemical pesticides, when chemicals began to be extracted from their botanical sources and were purified in laboratories. It was at this time that nicotine compounds were purified from tobacco, pyrethrums were extracted from flowers, and rotenone isolated from roots. In addition, cyanides were recognized as toxic compounds in the pits of some fruits.

During this era, chemical compounds were blended and produced for the purpose of pest control. In 1814, an inorganic compound of copper (II) acetoarsenite called "Paris Green" was introduced as a pigment. By 1867, Paris Green was widely sold as an insecticide and rodenticide. In fact, Paris Green paints even continued to be produced up until the 1960s.

Similarly, the Bordeaux Mixture was developed in the late 19th century to fight the Great French Wine Blight. Its mixture of copper (II) sulfate and calcium hydroxide was designed to combat fungal and mildew infections in vineyards.

It was during the Victorian era that traditional methods of pest control were formally investigated and put to the scientific method. As a result, all of the chemical compounds that were historically available in their botanical forms (e.g., rotenone in roots and pyrethrums in chrysanthemums) were purified for commercial and home use, and elemental compounds were blended to create more efficient pesticides. The humble beginnings of simple, natural repellents and physical pest controls grew into chemical and agricultural industries seeking out new and improved methods.

The Advance of Pesticides Through the 20th Century

The primitive tools now had scientific reasoning to explain their efficacy and identify their chemical formulations, moving them from the realm of natural extracts to synthesized pesticides, and signaling the rise of the chemical pesticide revolution. Pest control, which had begun with simple tools and methods, was refined over centuries and completely reborn during World War II. The late 19th and early 20th century world of the first synthetic organic chemicals gave rise to the first modern synthetic pesticides in the form of organochloride compounds.

Many organochloride compounds, such as BHC and DDT, were first synthesized in the 1800s, but their properties as insecticides were not fully discovered and exploited until the late 1930s. BHC (Benzene hexachloride) was first produced by the English scientist Michael Faraday in 1825, but its properties as an insecticide were not identified until 1944. DDT (dichlorodiphenyltrichloroethane) was first prepared by Othmar Ziedler, an Austrian chemist, in 1825, but the Swiss chemist Paul Hermann Müller did not discover DDT's insecticidal properties until 1939 - a discovery that led to Müller's award of the Nobel Prize in 1948.

By 1945, DDT was made available for agricultural applications. But the first signs of insect resistance to DDT began to appear in the 1950s. In 1962 Rachel Carson, a marine biologist and conservationist, published Silent Spring, a book that highlighted the detrimental effects of pesticides on the environment. The widespread popularity of Carson's book led to the establishment of influential grassroots organizations that called for greater environmental protections and stricter controls on pesticide use. Part of that call to change was the reduction or elimination of DDT and many other pesticides developed from the 1940s through the 1960s from the pest-fighting arsenal.

DDT remained in widespread use around the world until the 1980s, but its decline hastened once the U.S. Environmental Protection Agency (EPA) canceled most uses of DDT by 1972. Many other countries followed suit shortly thereafter by removing DDT from lists of approved agricultural applications. In 2004, the Stockholm Convention outlawed many persistent organic pollutants (POPs) and restricted the use of DDT to vector control (primarily for malaria). Despite increasing worldwide restrictions and bans on DDT, as of 2008, India and North Korea were still using DDT in agricultural applications. Today, India is the only country in the world still producing DDT.

Since the start of the production boom in the 1940s to present day, a huge catalog of thousands of insecticides, herbicides, and general pesticides was developed, including organochlorides (DDT, BHC), organophosphates (Parathion, Malathion, Azinophos Methyl), phenoxyacetic acids (2,4-D, MCPA, 2,4,5-T), Captan, Carbamates (Aldicarb, Carbofuran, Oxamyl, Methomyl), neonicotinoids (Imidacloprid, Acetamiprid, Clothianidin, Nitenpyram), and Glysophates.

The neonicotinoids are neuro-active insecticides, similar to nicotine compounds that were developed in the 1980s and 1990s. Of all the neonicotinoids, Imidacloprid has become one of the most abundantly used insecticides in the world. Patented in 1988 and registered with the EPA in 1994 by Bayer Crop Science, Imidacloprid works by disrupting the transmission of nerve impulses in insects by binding to an insect's nicotinic acetylcholine receptors, resulting in paralysis and death. Imidacloprid is highly toxic to insects and other arthropods, including marine invertebrates. It is considered to be moderately toxic to mammals if ingested at high dosages.

The acute toxicity and environmental fate of Imidacloprid and other neonicotinoid pesticides have been greatly debated since their adoption in the 1990s. Many studies have examined the persistence of neonicotinoids in water supplies and their ecological impacts on other environmentally and economically important arthropods. Studies published within the last two decades have linked bee colony collapse disorders with Imidacloprid and other similar pesticides. The most toxic pesticide in the world today for honey bees (genus Apis) is also the most commonly used insecticide in the world: Imidacloprid.

If Imidacloprid is the most widely used insecticide in the world, Glyphosate is the most widely used herbicide on Earth. Glysophate was developed by a Monsanto chemist, John E. Franz, in 1970. Roundup, as it was trademarked, quickly became one of the most popular herbicides in the world among both agricultural enterprises and home users. The mode of action for Glyphosate is to inhibit a plant enzyme that is integral to the synthesis of aromatic amino acids. The inhibition of the amino acid production affects primarily the growing regions of the plants, killing plants in their growth cycle but not in their seed stage.

In 1994, the Roundup Ready Soybean was commercially approved in the United States. This genetically engineered soybean was created to be resistant to glyphosate. These types of crops allowed for the use of glyphosate to control other pest plants without endangering the crop. The list of glyphosate-resistant crops has grown since the introduction of the Roundup Ready Soybean to include corn, canola, alfalfa, cotton, and wheat.

GMOs: The Future of Pest Control?

Genetically modified organisms (GMOs) have become widely used in the United States since their initial introduction in the 1990s. Genetically modified crops are grown by millions of farmers in dozens of countries. The predominant modified crops are soybeans, corn or maize, cotton, and canola.

GMO labeling is required in many countries but not in the United States. Scientists and economists argue that the potential benefits of GMO crops include reductions in the use of pesticides and other hazardous pollutants and an increase in the nutritional value and production of agricultural products. Opponents of GMOs claim that all the latent risks have not been adequately identified, especially the potential long-term impact of GMOs on human health and the environment.

The issue is not a question of whether genetically modified organisms should be used as a pest strategy. The truth is that genetic modification is already well established as the newest tool in the arsenal of pest management. It will be up to future generations to decide if the history of this nascent pest-management strategy will go the way of heavy metal pesticides and DDT, or if GMOs will become the ultimate solution for pest control.
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Modern pest management and control is an increasingly diverse science with thousands of different management strategies. Synthetic chemical pesticides, which were first deployed during the World War II era, are a relatively new development in an epic battle against pests and parasites.

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Although they will probably always be less celebrated than wars, marches, riots, or stormy political campaigns, books have at times been the most powerful influencer of social change in American life. Thomas Paine's Common Sense galvanized radical sentiment in the early days of the Revolution; Uncle Tom's Cabin by Harriet Beecher Stowe roused the North's antipathy to slavery in the decade leading up to the Civil War; and Rachel Carson's Silent Spring, which in 1962 exposed the hazards of the pesticide DDT, eloquently questioned humanity's faith in technological progress and helped set the stage for the environmental movement.

Carson, a renowned nature author and a former marine biologist with the U.S. Fish and Wildlife Service, or FWS, was uniquely equipped to create so startling and inflammatory a book. A native of rural Pennsylvania, she had grown up with an enthusiasm for nature matched only by her love of writing and poetry. The educational brochures she wrote for FWS, as well as her published books and magazine articles, were characterized by meticulous research and a poetic evocation of her subject.

"Things go out of kilter"

Carson was happiest writing about the strength and resilience of natural systems. Her books Under the Sea Wind, The Sea Around Us (which stayed on the New York Times best-seller list for 86 weeks), and The Edge of the Sea were hymns to the interconnectedness of nature and all living things. Although she rarely used the term, Carson held an ecological view of nature, describing in precise yet poetic language the complex web of life that linked mollusks to seabirds to the fish swimming in the ocean's deepest and most inaccessible reaches.

DDT, the most powerful pesticide the world had ever known, exposed nature's vulnerability. Unlike most pesticides, whose effectiveness is limited to destroying one or two types of insects, DDT was capable of killing hundreds of different kinds at once. Developed in 1939, it first distinguished itself during World War II, clearing South Pacific islands of malaria-causing insects for U.S. troops while being used as an effective delousing powder in Europe. Its inventor was awarded the Nobel Prize.

When DDT became available for civilian use in 1945, there were only a few people who expressed second thoughts about this new miracle compound. One was nature writer Edwin Way Teale, who warned, "A spray as indiscriminate as DDT can upset the economy of nature as much as a revolution upsets social economy. Ninety percent of all insects are good, and if they are killed, things go out of kilter right away." Another was Carson, who wrote to Reader's Digest to propose an article about a series of tests on DDT being conducted not far from where she lived in Maryland. The magazine rejected the idea.

Silent Spring

Thirteen years later, in 1958, Carson's interest in writing about the dangers of DDT was rekindled when she received a letter from a friend in Massachusetts bemoaning the large bird kills that had occurred on Cape Cod as the result of DDT sprayings. The use of the pesticide had proliferated greatly since 1945, and Carson again tried, unsuccessfully, to interest a magazine in assigning her the story of its less desirable effects. By 1958, Carson was a best-selling author, and the fact that she could not obtain an assignment to write about DDT is indicative of how heretical and controversial her views on the subject must have seemed. Having already amassed a large quantity of research on the subject, however, Carson decided to go ahead and tackle the issue in a book.

Silent Spring took Carson four years to complete. It meticulously described how DDT entered the food chain and accumulated in the fatty tissues of animals, including human beings, and caused cancer and genetic damage. A single application on a crop, she wrote, killed insects for weeks and months-not only the targeted insects but countless more-and remained toxic in the environment even after it was diluted by rainwater. Carson concluded that DDT and other pesticides had irrevocably harmed animals and had contaminated the world's food supply. The book's most haunting and famous chapter, "A Fable for Tomorrow," depicted a nameless American town where all life-from fish to birds to apple blossoms to human children-had been "silenced" by the insidious effects of DDT.

First serialized in The New Yorker in June 1962, the book alarmed readers across America and, not surprisingly, brought a howl of indignation from the chemical industry. "If man were to faithfully follow the teachings of Miss Carson," complained an executive of the American Cyanamid Company, "we would return to the Dark Ages, and the insects and diseases and vermin would once again inherit the earth." Monsanto published and distributed 5,000 copies of a brochure parodying Silent Spring entitled "The Desolate Year," relating the devastation and inconvenience of a world where famine, disease, and insects ran amok because chemical pesticides had been banned. Some of the attacks were more personal, questioning Carson's integrity and even her sanity.

Vindication

Her careful preparation, however, had paid off. Anticipating the reaction of the chemical industry, she had compiled Silent Spring as one would a lawyer's brief, with no fewer than 55 pages of notes and a list of experts who had read and approved the manuscript. Many eminent scientists rose to her defense, and when President John F. Kennedy ordered the President's Science Advisory Committee to examine the issues the book raised, its report thoroughly vindicated both Silent Spring and its author. As a result, DDT came under much closer government supervision and was eventually banned. The public debate moved quickly from whether pesticides were dangerous to which ones were dangerous, and the burden of proof shifted from the opponents of unrestrained pesticide use to the manufacturers.

The most important legacy of Silent Spring, though, was a new public awareness that nature was vulnerable to human intervention. Carson had made a radical proposal: that, at times, technological progress is so fundamentally at odds with natural processes that it must be curtailed. Conservation had never raised much broad public interest, for few people really worried about the disappearance of wilderness. But the threats Carson had outlined-the contamination of the food chain, cancer, genetic damage, the deaths of entire species-were too frightening to ignore. For the first time, the need to regulate industry in order to protect the environment became widely accepted, and environmentalism was born.

Carson was well aware of the larger implications of her work. Appearing on a CBS documentary about Silent Spring shortly before her death from breast cancer in 1964, she remarked, "Man's attitude toward nature is today critically important simply because we have now acquired a fateful power to alter and destroy nature. But man is a part of nature, and his war against nature is inevitably a war against himself? [We are] challenged as mankind has never been challenged before to prove our maturity and our mastery, not of nature, but of ourselves."

One of the landmark books of the 20th century, Silent Spring' s message resonates loudly today, even several decades after its publication. And equally inspiring is the example of Rachel Carson herself. Against overwhelming difficulties and adversity, but motivated by her unabashed love of nature, she rose like a gladiator in its defense.

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How a courageous woman took on the chemical industry and raised important questions about humankind's impact on nature.

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Search America's historic newspaper pages from 1770-1963 or use the U.S. Newspaper Directory to find information about American newspapers published between 1690-present. Chronicling America is sponsored jointly by the National Endowment for the Humanities external link and the Library of Congress. Learn more

No More Mosquitoes ...
BY ELIZABETH PRITCHARD
Back in America, miraculous
DDT may do a home-front
job equal to its battle record
Spring and housecleaning time are coming.
The housewife is stirring. She's getting
out the rug beater, readying the scrub pail
and thinking how to shove the piano over
where the sofa is now. But in 300,000 South
ern homes this year something new will be
added. It's DDT. the miraculous insect poi
son which has been doing such a good battle
front job. Many homes in 11 Southern
states will be sprayed - a trial run
against malaria that may become annual
after the war.
Any morning, now, if a Georgia housewife
hears a knock on the door and sees men and
spraying equipment in the yard she probably
won't be surprised. In fact, she'll say, "Good
morning. You're the ones I'm expecting?"
"That's right, ma'am. We're here to spray
DDT. It'll take only half an hour."
Malaria Sarioua Problem
' 'Come right in, then - but don't you spot
my furniture!" She needn't worry.
In some 100 counties of the South, malaria
is a particularly serious problem. Authorities
are combatting any possibility that this
insect-borne disease will sweep that area.
The Public Health Service, Army, WPB and
other agencies have scraped up enough DDT,
although it's not generally available to civil
Insect pests will get no quarter when this crew sprays homes
ians, tb protect every home. Spraying will be
done between March and June.
The initials DDT stand for a mouthful
of chemical terms: dichloro-diphenyl-trichlo
roethane. When used properly it kills many
of our enemy insects, household pests - es
pecially the mosquitoes and fleas which spread
malaria and typhus fever.
Here's how the anti-mosquito campaign in
the South is organized. Already the necessary
100 tons of DDT powder have been gathered.
One thousand men have been trained as
spraying crews. They'll soon be invading
that malarial zone in 400 mobile units -
including converted jeeps and gun carriers.
Crews will cover household goods with tar
paulins, stow away dishes and raw foods.
Walls and ceilings, kitchens and pantries
then can safely be sprayed with DDT. It
wipes off windows easily. It leaves no mark
on curtains, mattresses and other tex
tile furnishings. In fact, mattresses can
be left on the beds and sprayed to kill
any bothersome insects.
Sprayed under pressure 18 inches from the
wall surfaces, DDT penetrates the finest
crevices. There it dries and leaves, tiny crys
tals. When insects come in contact with these
crystals their nervous systems are destroyed
and they soon die.
An amazingly small amount of DDT goes
a long way. Furthermore, its toxic effects
last a long time. A good spraying in these
Southern homes now will last all summer and
far into next winter.
Already DDT has successfully waged bat
tle for our armed services against those two
wartime diseases: typhus fever and malaria.
It stopped a disastrous epidemic of typhus in
Italy, and now there is enough DDT louse
powder to prevent an epidemic among the
liberated peoples of Europe.
* In jungle areas, DDT is sprayed on tent
walls and used in an oil mixture to kill mos
quito larvae in water.
Many agricultural uses have been found for
DDT. It is effective against codling moths,
cabbage worms, Jap beetles, flies and ants.
Its chemical potentialities have only been
scratched. Much research must be done, how
ever, before DDT can be used extensively in
agriculture. Although it kills harmful insects,
it may also kill some beneficial ones, and upset
a natural balance.
Experts have found that, under proper
conditions, it is no more harmful to human
beings than other common insecticides. When
used as a louse-powder it can safely touch the
skin; when diluted properly as a spray it can
be inhaled without harmful effects.
Public health officials believe DDT will
become one of the foremost health aids to
human beings after the war. Housewives
probably will get DDT sprays for their own
use. DDT even may be mixed with wall
paints some day to provide a perpetual death
trap for insect house pests.
The TH^^Cladiron
irons shirts so amazingly because
~~ the patented roller was huilt for sleeves
Just slip the shirt sleeve right
over the Gladiron roll-and four min
utes later you've finished the shirt -
faster and easier than you ever
dreamed ironing could he.
Iron children's clothes or slacks
just as simply-and iron flatwork as
fast as you can guide it through. You
can steam velvets-press trousers-
freshen ties-and iron delicate laces
and doilies-all without strain or effort.
The Thor Gladiron is the won
derful iron that stands while you sit
down. It takes the backache out of
ironing day. No hours of standing
when you have a Gladiron, no press
ing down, no heat in your face.
*Ask your Thor Dealer to let you
sign his Priority Register for one of
the first Gladirons available. If you
don't know his name,
write us.
HURLEY MACHINE DIVISION
Electric Household Utilities Corp.
54th Avenue and Cermak Koad, Chicago 50. III.
c om.
c. m. u. co"*.

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Evening star. [volume] (Washington, D.C.) 1854-1972, February 25, 1945, Page 9, Image 62

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Evening star. [volume] (Washington, D.C.) 1854-1972, February 25, 1945, Page 9, Image 62, brought to you by Library of Congress, Washington, DC, and the National Digital Newspaper Program.

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The Kennewick courier-reporter. [volume] (Kennewick, Wash.) 1939-1949, May 30, 1946, Page 4, Image 4

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The Kennewick courier-reporter. [volume] (Kennewick, Wash.) 1939-1949, May 30, 1946, Page 4, Image 4, brought to you by Washington State Library; Olympia, WA, and the National Digital Newspaper Program.

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DDT BANNED IN U.S. ALMOST TOTALLY, EFFECTIVE DEC. 31 (Published 1972)

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Environmental Protection Admr Ruckelshaus on June 14 bans all uses of DDT, contending in 40‐page rept that ‘the evidence of record showing storage of DDT in man and magnification in the food chain...is a warning to the prudent that man may be exposing himself to a substance that may ultimately have a serious effect on his health’; says DDT could persist in soil for yrs and even decades, and also in aquatic ecosystems; adds that it could become attached to eroding soil particles and contaminate water supplies; says chem impairs reproductive processes of birds and fish and that experiments on laboratory animals have shown that DDT causes tumors, fact which raises possibility that it may cause cancer in human beings; history of chem as well controversy over its effects revd; diagram of organic structure of DDT