GOOD GENES The Danforth Center attracts a diverse group of scientists including biochemists and chemists, such as research associate Zhihong Zhang, who inspects transgenic A. thaliana plants for interesting phenotypes. MIKE BIZELLI/DANFORTH CENTER PHOTO

Research at the not-for-profit Danforth Center focuses on providing food for the world's rapidly expanding population in an environmentally friendly and sustainable way. Its mission extends beyond the food, nutritional, and health needs of the developed world: The center has dedicated 10% of its resources and facilities to research specifically related to the needs of agriculture in developing countries. This mission has drawn a diverse group of biochemists, chemists, geneticists, and plant pathologists to the center.

Although they share a common mission, these investigators work on projects that range from studying the basic biology of plant roots to understanding plant defense mechanisms to leveraging biotechnology to improve the yield, disease resistance, and hardiness of crops.

When asked why they came to the Danforth Center, investigators cite the rich, collaborative environment and the strong focus on plant sciences. But its commitment to the developing world is what makes the center unique, they stress. And they credit the man driving that commitment, Danforth Center President and plant biologist Roger N. Beachy, with drawing them there.

"Roger's scientific reputation is outstanding," says Charles J. Arntzen, chairman of the department of plant biology and director of the Arizona Biomedical Institute at Arizona State University and former president of the Boyce Thompson Institute for Plant Research in Ithaca, N.Y. "And he has all the right motivations. The Danforth Center is lucky to have him."

Beachy--whose research at Washington University, St. Louis, during the 1980s led to the creation of the first transgenic crop, a virus-resistant tomato--spent seven years at Scripps Research Institute before returning to the Midwest in 1999 to head the Danforth Center. "At the time, private institutions were not making plant biology a priority," he says. "I welcomed the challenge of starting something new in an area of science that will deeply impact human health and welfare."

The center's mission, Beachy emphasizes, is built on a commitment to basic, interdisciplinary, and collaborative plant science. "By studying how plant roots respond to stresses in the soil, we hope to make crops more resistant to drought or salinity," he says. "By studying how plants produce vitamins and phytochemicals, we hope to enrich the nutritional quality of crops. And by studying how certain plants defend themselves against pests and pathogens, we hope to allow farmers to reduce the use of agrochemicals," he adds.

The Danforth Center was founded in 1998 in partnership with the Missouri Botanical Garden; Monsanto; Purdue University; the University of Illinois, Urbana-Champaign; the University of Missouri, Columbia; and Washington University. The center was created with funding from Monsanto's philanthropic arm, the Monsanto Fund, and the Danforth Foundation, a St. Louis-based philanthropic organization. In addition, the state of Missouri provided generous tax credits and Monsanto provided the land on which the building was built. Research grants, contracts, and endowment income will fund future research, Beachy says.

Many states and regions have looked to high-tech and biotechnology research to invigorate their local economies. But in the late 1990s, a group of St. Louis business, academic, and government leaders noted that the region's real strengths lay not just in high-tech or biotech but in plant and agricultural sciences.

These strengths are deeply rooted. More than half of the nation's food is grown within 500 miles of St. Louis. Washington University and the Missouri Botanical Garden boast top-notch research in plant science and biodiversity, respectively. St. Louis is also home to a number of companies with agricultural roots--including Monsanto, Nestle Purina, and Anheuser Busch--as well as the American Soybean Association and the National Corn Growers Association. In addition, the University of Missouri, Columbia; the University of Illinois, Urbana-Champaign; and Purdue University each have strong agriculture schools.

"The Danforth Center is intended to be a catalyst to encourage research collaboration in an area where the Midwest has traditionally been strong--plant and agricultural science," Beachy says. "Our regional partnership is an important component of the mission of the Midwest: food production, safety, and nutrition."

The links with partner institutions provide an opportunity to forge multi-institution collaborations. Many of the center's investigators serve as adjunct faculty at partner institutions, fostering collaborations beyond the center's walls.

"The Danforth Center presents a phenomenal opportunity to collaborate with people from a variety of different disciplines," says Karel R. Schubert, who is both an investigator in the Danforth Center and its vice president for technology management and science administration. "We synergize each other's research."

In addition, the Danforth Center aims to be a resource for scientists and students in developing countries. The center hopes to help its more than 40 foreign postdocs and trainees--who represent more than 20 different countries in Eastern and Western Europe, Africa, India, the Asia-Pacific region, and Latin America--develop the intellectual and technical skills relevant to the needs of agriculture in their home countries.

The center, housed in a three-story building with a large, central atrium, features state-of-the-art plant growth facilities that allow researchers to see how disease or genetic changes affect plant phenotypes. These include a 15,000-sq-ft greenhouse and environmentally controlled growth rooms and chambers. There are also X-ray crystallography, mass spectrometry, and integrated microscopy facilities.

The building houses 160 people, including 14 principal investigators. Faculty members' research projects span the gamut from basic plant biology to crop improvement.

Beachy's own research focuses on how plant viruses infect cells, replicate, and spread. His lab has shown that transgenic tobacco plants carrying the gene for the coat protein of tobacco mosaic virus containing a single amino acid substitution are extremely resistant to the virus. Beachy and his coworkers have found that expression of the mutant coat protein stymies production of a viral protein necessary for cell-to-cell spread of infection. His team is using the Danforth Center's live-cell imaging resources to track the movement of the latter protein during the course of viral infection and is working to solve its three-dimensional structure. Beachy hopes that an understanding of how these viruses infect and spread will eventually lead to new methods of preventing viral infection in transgenic plants.

Within Beachy's lab, Schubert is using genetic engineering to enhance the content and bioavailability of folate in the model plant Arabidopsis thaliana. Folate is found naturally in green leafy vegetables and legumes, and a deficiency during pregnancy can lead to neural tube defects. Neural tube defects cause damage to a fetus' brain and spinal cord, but are relatively rare in the U.S. and other industrial countries where dietary supplementation and fortification of packaged foods with folic acid is common. Beachy and Schubert hope to create folate-fortified rice for growth in developing countries, where folate supplements or folate-fortified foods are not available and the rate of neural tube defects is more than 10 times that in the U.S.

"The Danforth Center presents a phenomenal opportunity to collaborate with people from a variety of different disciplines."

RESEARCHERS at the Danforth Center are also studying how plant roots supply important nutrients and respond to stress. Geneticist Daniel P. Schachtman's lab is examining how plant roots take up minerals from the soil and is determining how plants adapt these mechanisms to problem soils.

In many areas of the world, salty irrigation water and salt-damaged soils severely limit crop production. Plants growing in saline soils take up excess sodium and potassium, which stunts their growth. Reducing uptake of sodium allows some plants to grow faster and produce more. Since plants are likely to rely on potassium transport proteins for sodium uptake, Schachtman's lab is working to delineate function and ionic selectivity for the potassium uptake protein class of potassium transporters in Arabidopsis.

Members of his lab have also been searching for plant proteins that take up zinc from the soil by using yeast cells deficient in zinc uptake and for plant genes that restore the yeast cells' ability to take up zinc. They have found two such putative zinc transporters in rice using this method. In addition, Schachtman's lab is looking for changes in zinc uptake and seed zinc content in transgenic barley overexpressing an Arabidopsis zinc transporter. By some estimates, nearly half of the world's people fail to obtain adequate amounts of zinc from their diet. This work may lead to modification of plant food staples so that they are better at taking up zinc from soils and to increased zinc bioavailability in foods.

Biochemist Thomas J. Smith uses the tools of X-ray crystallography to understand how pathogens infect and harm plants--and in doing so, he hopes to provide new ways of controlling such pathogens. His lab is studying a rare example of symbiosis between a virus and its fungal host. The UMV4 virus permanently resides inside its host of choice--Ustilago maydis, or corn smut--and relies on the fungus for its replication and survival. In return, the virus produces a 105-amino acid toxin called KP4 that kills competing strains of fungus. Structural studies and biochemical assays show that the toxin kills by blocking calcium channels in foreign fungi. The group hopes to use the information to make plants resistant to other fungi, Smith says. "We hope these studies will reveal the Achilles heel of these fungi."

Unusual seed oils that might have useful industrial applications are the focus of the laboratory of biochemist Jan G. Jaworski. He hopes to use information gleaned from the study of seed oil metabolism to modulate their composition.

His lab is investigating structure-function relationships in 3-ketoacyl synthases, a class of plant enzymes that participate in fatty acid and oil biosynthesis and elongation. The researchers have cloned, purified, and characterized 3-ketoacyl-ACP synthase III from spinach, a soluble protein that catalyzes the first condensation reaction. In addition, they are working to characterize a membrane-bound condensation enzyme from Arabidopsis, the 3-ketoacyl-CoA synthase FAE1 KCS.

In a separate project, funded by Dow, Jaworski is using such metabolic information to guide insertion of genes from exotic plants into Arabidopsis that enable production of seed oils of unique and industrially interesting compositions. "Such plants could represent a renewable, domestic source of chemical feedstocks and polymer precursors," Jaworski says. Plants could also provide novel chemical feedstocks not available from petroleum-based sources, he adds.

The Danforth Center is also home to the International Laboratory for Tropical Agricultural Biotechnology. Since its founding in 1991 by Beachy and Director Claude M. Fauquet, ILTAB has sought to improve tropical crops, to develop the research capacity of developing countries by training scientists and transferring technology, and to coordinate global biotechnology research on tropical crops.

ILTAB's current focus is the tuber cassava, also known as manioc, a dietary staple worldwide but most important to African farmers, who produce 90 million metric tons of cassava annually. In Africa alone, an estimated 35–50 million metric tons of cassava--representing 40–55% of annual crop production--are lost per year to viral diseases, Fauquet tells C&EN. In the absence of a winter season, these viruses flourish year-round. Cassava is propagated from cuttings taken from older plants, allowing viruses to spread rapidly. These unique conditions lessen the effects of conventional means of control, Fauquet says.

Although cassava represents food security for many people, it has limited nutritional benefit. It provides negligible amounts of protein, a scarce commodity in many regions of Africa. And because cassava flour has a different biochemical composition and lacks the proteins required for bread production, Africa must import tons of wheat flour each year to meet its bread needs.

Fauquet and ILTAB are working to create transgenic cassava varieties that are resistant to viral disease, have improved starch content, and contain more protein. To do so, the Danforth Center negotiated royalty-free rights to the enabling genetic engineering technologies from Monsanto. The agricultural biotechnology firm granted the rights with no strings attached, Fauquet notes.

"I don't know of any other research center that I have ever visited that has a greater potential contribution to the well-being of the world."

BIOTECH FIRMS like Monsanto have little commercial interest in developing world crops like cassava, so they lose nothing by this kind of generosity, Beachy notes. But many Danforth Center researchers are working to create technology of interest to farmers in both developing and developed countries. It's crucial that the center share the benefits of technology developed there with scientists and farmers in both rich and poor nations, Beachy adds.

So Beachy has instituted an intellectual property policy that takes inspiration from its underlying focus on creating technologies and tools to benefit the developing world. The Danforth Center's Office of Technology Management is charged with making sure that future licensing arrangements for technology developed at the center are crafted in an equitable way.

The Danforth Center works with a range of different companies, Schubert points out. But the center retains the rights to any technology developed to address needs in developing countries. A number of universities and research institutions are warming up to the idea of retaining intellectual property rights for humanitarian uses, notes Gary H. Toenniessen, director of food security at the Rockefeller Foundation. The Danforth Center is leading the charge.

Arizona State's Arntzen agrees. "Roger [Beachy] is pioneering innovative intellectual property management geared to helping both the developed and the developing worlds benefit from agricultural research," he says. "He is creating a good model for how it can and should be done."

Beachy sees the Danforth Center as a model for more than just intellectual property management. He hopes the center will assume a place at the forefront of plant science research, a field that he and founders of the Danforth Center--as well as many other plant scientists--think is just as vital to the future of the world as medical research.

FUNDING
An Independent Research Center

The Donald Danforth Plant Science Center was conceived in 1997 by William H. Danforth, chancellor emeritus of Washington University, St. Louis. Danforth envisioned an independent plant sciences center that would be the centerpiece of the "BioBelt"--a hotbed of plant and life sciences research, investment, and business opportunity in the Midwest.

Monsanto and the Missouri Botanical Garden quickly signed on as partners, followed by Purdue University; the University of Illinois, Urbana-Champaign; and the University of Missouri, Columbia. The Danforth Foundation anted up $60 million for the center's construction; the Monsanto Fund, the firm's philanthropic arm, contributed $50 million; and Monsanto donated the land on which the center was built.

Although Monsanto and the Monsanto Fund provided major financial support for the creation of the Danforth Center, the center's president, Roger N. Beachy, is quick to defend the center's independence. "The challenge is to maintain corporate relationships while retaining the openness of academia," he says. "We hope we're a model for institutions seeking this balance."

In addition to representatives from each of its six founding institutions, the center's 16-member board of trustees includes 10 outside members such as biochemist Bruce Alberts, president of the National Academy of Sciences. An external scientific advisory board has also been set up.

Perhaps the most telling evidence of the Danforth Center's independence is the diverse sources of funding its researchers have landed. Danforth Center investigators have entered research agreements with a number of companies--including Monsanto's competitors. In addition, its researchers receive support from a variety of federal agencies, including the National Science Foundation, the National Institutes of Health, the National Aeronautics & Space Administration, and the Department of Energy.

Outsiders confirm Beachy's claim of independence. "The basic governance of the center gives them the independence that they need," says Gary H. Toenniessen, director of food security at the Rockefeller Foundation. "The Danforth Center is just as independent as any other public-sector research institution."

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