The Divergence research program is focused on parasites, especially nematodes or roundworms, a major cause of economic losses in agriculture, as well as morbidity and mortality in humans and domestic animals.

Plant parasitic nematodes
Animal parasitic nematodes
Human parasitic nematodes

Plant parasitic nematodes
Nematodes are one of the world's major agricultural pests, causing an estimated $80 billion in worldwide crop damage annually. Furthermore, current nematicides are environmentally dangerous, expensive, and difficult to apply. Nematode infested crops with major economic losses include soybeans, potatoes, bananas, cotton, citrus, strawberries, tomatoes, coffee, carrots, peppers, turf, and greenhouse ornamentals. An exhaustive list of nematode damage includes nearly every cultivated plant.

Current nematode control depends on highly toxic pesticides, all of which have been classified for restricted use or slated for elimination by the Environmental Protection Agency (EPA). Methyl Bromide, the primary means of nematode, fungus, and bacterial control for California fruit and vegetable producers, is a neurotoxin, the use of which will be terminated in 2005. Other major nematicides include aldicarb, a human neurotoxin responsible for ground water contamination, and 1,3-dichloropropene, a human carcinogen. Both are restricted use chemicals currently under EPA review.

It is estimated that the current market for nematicides is less than $1 billion each year worldwide; however, an analysis of the economic impact of nematodes and growers' decision-making suggests that, given safe control methods, the market could become a multi-billion dollar market annually. This market is comparable to the current markets for insecticides and fungicides that have reached $9.1 billion and $5.5 billion, respectively.

Specific markets where Divergence’s innovations could be applied include novel mode-of-action nematicides delivered by soil, foliar, or seed treatment methods and resistance traits expressed in transgenic crops.

Impact of Nematodes on Crop Losses
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Animal parasites
Parasites (both endo-parasites such as nematodes and ecto-parasites such fleas, ticks, and flies) pose many problems for livestock and companion animals. Diseases caused by nematodes include heartworm in dogs, a fatal disease if untreated; intestinal roundworm infections of cattle, sheep, and goats, which result in severe economic losses in the livestock industry; and Trichinella infection, a disease of pigs which can infect humans who eat undercooked pork. Drugs used to control nematode parasites of animals include: the ivermectin class of compounds; with sales of over $500 million annually; milbemycin, with sales of over $100 million; and the off-patent albendazole class.

Resistance to both ivermectin and albendazole drugs is widespread in sheep and goat intestinal roundworms in South America, South Africa, Australia, and now North America. has also appeared in nematode parasites of cattle and horses. This inability to control nematode infections has caused severe economic dislocation and will continue to cause losses unless alternative compounds are brought to market.
Specific markets where Divergence’s innovations could be applied include novel mode-of-action anthelmintics effective against parasites resistant to other drug classes, molecules with dual-action efficacy such as endo- and ecto-parasite control (endecticide), and novel vaccine targets for Strongylid control such as gene products essential to nematode digestion.

Impact of Nematodes on Animal Health
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Human parasitic nematodes
Nematodes are major parasites of humans, infecting nearly three billion people worldwide, mainly in developing countries. Diseases caused by nematodes include hookworm infection, a major cause of anemia and stunted growth in children in tropical countries; Ascariasis, a gut roundworm infection, which affects over one billion people and results in decreased quality of life; and elephantiasis or filariasis, an infection of the lymphatic system resulting in grossly swollen and scarred extremities.

Vaccines are likely to be crucial in decreasing the incidence of the major geohelminths (hookworm, Ascaris, and whipworm). There are currently no effective vaccines for human parasitic nematodes. A major need in anthelmintic pharmaceuticals for humans is the development of a compound effective for the adult stage of filarial infections including lymphatic filariasis (elephantiasis) and riverblindness. Major campaigns underway to control or eliminate these diseases could be greatly accelerated by the availability of such a compound.

Specific markets where Divergence's innovations could be applied include novel mode-of-action macrofilaricides and novel vaccine targets such as gene products essential to nematode digestion. Application of Divergence technology to global health will likely require partnerships with the non-profit and government sector, interactions that could be synergistic with for-profit development of products for agricultural and veterinary applications.

Briefing Paper: The Importance of New Drug Discovery to Control
Impact of Nematodes on Human Health
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Top panel: Root knot nematode damage to cotton. Untreated (left) vs. fumigation with 1,3-dichloropropene (right). Photograph by Jonathan D. Eisenback, Ph.D. from the Nemapix Volume I collection.

Middle panel: Root knot nematode damage to carrot roots includes forking (left) and stunting (right). Photograph by Jonathan D. Eisenback, Ph.D. from the Nemapix Volume I collection.

Bottom panel: The dog hookworm, Ancylostoma caninum, attaches to capillaries in the wall of the intestine, where it sucks blood. Photograph by Jonathan D. Eisenback, Ph.D. from the Nemapix Volume I collection.