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Dr. Thomas C. Sparks’ Swarm of Ideas

Mon, 12/21/2009 - 9:12am
Paul Livingstone

Dr. Thomas C. SparksBy keeping an open mind and irrepressible optimism, the 2009 R&D Magazine Scientist of the Year helped Dow AgroSciences pioneer a new, green insect control technology.

By some estimates, there are more than a million insect species in this world. Only a small percentage of this number is detrimental to the quality of our lives, but these are the species that drive research by scientists like Dr. Thomas C. Sparks, R&D Magazine’s 44th Scientist of the Year. An entomologist’s job is to know these insects, even down to the molecular level, to discover ways to keep them from destroying a very precious commodity: our food.

Most of us take for granted the quantity and quality of the food we eat. It wasn’t always this way. Before the advent of industrial fertilization and pest control, adequate crop production was under constant threat from weather changes and pests. Now, with more than 6 billion people to feed worldwide, careful management of agricultural resources is a requirement.

Sparks didn’t always have to view insects as a pest. In fact, his early research in entomology focused on beneficial insects, not the pests he would later have to contend with. He grew up in the lush Central Valley region of California, where fresh, quality food was always in healthy supply and there were plenty of insects around. What he learned about food and nature led him to chemistry coursework in college in the 1970s, but he soon switched to biology. Sparks earned his bachelor’s degree in biology at California State Univ., Fresno, and his doctorate in entomology, toxicology and physiology at the Univ. of California, Riverside, in the well-known laboratory of Dr. Bruce Hammock, where he completed key research on hormones that would guide him into the unexplored regions of entomological science.

As Hammock recalled to Kathy Keatley Garvey of Univ. of California, Davis recently, Sparks enrolled at UC Riverside to study biological control. “This interest soon took a more physiological and biochemical turn,” he says. “Tom had broad interests even then, ranging from synthesis of juvenile hormone analogs as green pesticides to resistance management, to his thesis work on the fundamental biochemistry of how butterflies and moths undergo metamorphosis.” “Interacting with Tom Sparks was a delight,” says Hammock, an entomologist who served as Sparks’ major professor at UC Riverside before joining the UC Davis faculty in 1980. “Tom trained me as much or more than I trained him.”

From his work in California, Sparks immediately moved into a teaching position in the Dept. of Entomology at Louisiana State Univ. He reportedly advanced from assistant to full professor in record time and was well-respected for his teaching ability. His toxicology course, in particular, was considered top-notch. In academia, he continued pioneering research on juvenile hormone esterase, an enzyme critical to the regulation insect development and a target for agrochemicals. Others studied this hormone before him, but his work was among the most important, helping spawn nearly 500 scientific papers on this topic.

An extended professorship, however, was not Sparks’ fate. Interested in new ideas in insect research, and eager to satisfy his instinct to invent, he joined Dow AgroSciences, Indianapolis, Indiana. With Dow, he was able to take advantage of the strong collaboration between chemists and biologists and begin his groundbreaking work in insecticide development. The focus of his efforts was to develop the recently discovered class of large molecules called spinosyns. This fermentation-based chemistry has rapidly transformed the insect control industry thanks to a ability to control agricultural and medical pests without the environmental and human impact normally associated with such products.

“At the time I joined they had discovered spinosyn chemistry. To me it was one of coolest, most exciting molecules I’d over seen. It really is one of the neatest chemistries extant,” says Sparks, who has spent the last 20 years examining these types of large molecules. “I saw that and said to myself that this is going to be a product.”

From the beginning, the efforts by Sparks and many others at Dow hinged on the assumption that they could do better than nature, that they could create new molecules with broader spectrums of reaction. Sparks’ knowledge of quantitative structure activity relationships was perfectly suited to the development of spinosyns, and computer-assisted discovery methods were successfully used to pioneer new chemistries. He formed the Macrolide Research Group that coordinated spinosad-related R&D at Eli Lilly and Dow for several years, and the effort has produced numerous successful products. Even after this group finished its work, Sparks continued his experimentation with these chemistries.

“I have the very good fortune of working with some really world-class scientists. If you don’t have a solid ground of knowledge and people with vision then science is much harder,” says Sparks. “I really think science is fun.”

Applying artificial neural networks
In what may soon become Sparks’ most important achievement so far, he has advanced this field by resolving a previously intractable molecular problem through the computational discipline of artificial neural networks. The problem was this: computer-aided modeling and design tools which had guided prior spinosyn development had run up against a wall. The molecules had become simply too complex to design using linear methods. He hit upon a solution during a discussion with a friend who was designing a robotic vacuum cleaner that was able to “learn” from its surroundings by using programming constructs that mimic the properties of biological neurons. Inexpensive artificial neural network programs were available, but they had never been used to help develop synthetic molecules.

Sparks, who was at UC Riverside during the silicon revolution, and knew the potential of advanced computing tools, put one such program, Braincel, to work on an advanced spinosyn problem, asking small questions about minute changes in molecular structure.

“It basically took the problem, shrunk it down, and simplified it. A, is there pattern? B, if we set the problem up correctly we get an answer,” says Sparks. Eventually, the answers become a panel of experts that gauge the likelihood that a chemistry will work. The effort required a litany of researchers; one of Sparks colleagues needed two months to deconstruct the molecule he designed, and still more time to reassemble and synthesis the pieces to form spinetoram, which represents one of the most advanced insecticides to reach the market. Derived through the fermentation of a natural soil organism followed by chemical modification, it impacts the environment in the same way a biological product does, yet operates with the efficacy of a synthetic technology.

Registered with the EPA’s Reduced Risk Pesticide Initiative, spinetoram can be used in a variety of crops, at low rates, and with minimal impact on mammals or beneficial insects. Some estimates claim that spinetoram will eliminate 1.8 million pounds of organophosphate pesticides used in tree nut and fruit crops in just the first five years of use. Without the efforts of Sparks and his team, this chemistry would have been far more elusive. And few people appreciate the risks of not finding such molecules—overuse and improper use inevitably cause a decline in existing molecule design.

“Not only are the spinosads now major green insecticides, but Tom introduced a new method of doing structure optimization in exceptionally complex molecules,” Hammock says. “This basic innovation extends far beyond agricultural chemistry to macrolide chemistry for the development of antibiotics and other natural products chemistry.”

Piecing the puzzles together
A 30-year member of the Entomological Society of America and the American Chemical Society, Sparks has been recognized with numerous accolades, including a Merck Research Development Award, several Dow Chemical awards, an Entomological Society of America Outstanding Graduate Student Award, a National Institutes of Health postdoctoral fellowship, an Arthur E. Schwarting Award for Best Paper in 2006, and the 2008 EPA Green Chemistry Award. He has also been successful on the intellectual property front, with several patents or patents pending. His reputation as a teacher is reflected in his nearly 100 invited lectures worldwide and a great many chemists who are now conducting research with the tools and methods Sparks has pioneered. After more than 130 published articles and breakthroughs in cheminformatics, insect endocrinology, insect biogenic amines, and high throughput screening, Sparks continues his mission of discovery. He was recently promoted to Advisor at Dow AgroSciences, a position reserved for only a few scientists who have distinguished themselves by making significant contributions to both science and The Dow Chemical Company.

Keith Wing, a former Hammock graduate student who is now a senior research associate for DuPont Central Research and Development, Wilmington, Del., praised Sparks’ selection as Scientist of the Year. “Tom has been a great friend and a very accomplished scientist and social contributor, especially with his work on the spinosad chemistry,” he said. “I have always admired his diligence, candor, keen insights, and creativity.”

While Sparks, an enthusiastic reader of history and a writer, is gratified to know that his work at Dow will provide growers with better options and address pest problems worldwide, but he sees his breakthrough as just a piece in a larger puzzle. Feeding the world is a task that will require a steady stream of discovery, and one that has to build on the lessons of the past. “We will need further breakthroughs in agronomy, weed science, pest management, a whole litany of areas,” he says. “It really is a high-tech enterprise all the way around.”

However, Hammock says that Sparks’ work has had a great impact.

“As scientists, we all expand human knowledge, but few of us really have a direct impact on the planet,” said Hammock. “Tom is one of the lucky few who not only contributed to basic science, but can point to his work on spinosads and say ‘I made the world a better place.’”

Published in R & D magazine: Vol. 51, No. 7, December, 2009, pp.6-7.

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