WSU vies for Gates grant

A clarion call was issued last year to researchers nationwide: help solve today’s most threatening global health problems. Now, Washington State University researchers are among those applying to take on the challenge.

The process began when Bill Gates announced a $200 million grant to the National Institutes of Health, which will help establish and administer grants for the Grand Challenges in Global Health Initiative. The project began with over 1,000 ideas submitted by scientists in 75 countries. Those ideas were then distilled down to what’s described as today’s 14 most daunting global health challenges.

Last fall, researchers were invited to submit proposals by Jan. 9, but the selection process will continue throughout the year with the final awards to be presented around October 2004. Among those letters of intent was one from WSU’s College of Agricultural, Human and Natural Resource Sciences but intricately woven with the work of many other departments and researchers associated with WSU.

“We’re trying to get the most creative minds in the world to focus on making these dramatic breakthroughs,” said Dr. Richard Klausner, director of the global health program for the Bill & Melinda Gates Foundation, in an article in the Seattle Post-Intelligencer newspaper. “It’s high time that the world’s scientific community, which has contributed so much to the medical progress achieved in the last century, turns its creative attention to solving the enormous health problems of the developing world.”

Banking on ag expertise

Proposing a project specifically tailored for Grand Challenge No. 9 is Jim Cook, interim dean of the College of Agricultural, Human and Natural Resource Sciences. The challenge — to create a single, staple plant crop with a full range of bioavailable nutrients — fits well within the structure and expertise already in place at WSU.

Recent establishment and funding of a Biotechnology Initiative further opens the door for WSU to tackle goal No. 9, which emphasizes the use of transgenesis, biochemistry, selective breeding of plants and other technologies. The goal is to provide life-sustaining combinations of micronutrients, vitamins and amino acids in local crops such as rice, wheat, sorghum, potatoes, maize, bananas, etc.

WSU Vice Provost for Research Jim Petersen said, “Much of what happens at a land-grant institution — our work on the biochemistry of plants, ranging from food production to the production of medicinal products and vaccines, to the minimization of insect impacts on foods to the use of animal models to understand all these interactions — can apply to many of the Grand Challenges, but the one we have the most expertise in is No. 9.”

Indeed, across campus, pockets of researchers are uncovering the secrets of genetic coding and successful transgenesis — taking genes from one species (bacteria, plant or animal) and inserting them into another to produce a specific result.

Until recently, selective breeding was the only way to attain desired characteristics in animals and plants. But due to great progress in genomic research over the last decade, it has now become possible to introduce foreign genes into crops to improve resistance or tolerance to drought, pests and herbicides as well as increase productivity and other factors. Some plants have even been designed to produce synthetic polymers, such as plastics, and animal proteins, such as insulin.

Biopharming: Making plants that make medicines

Advances in genomics also led to the birth of biopharming, an emerging field in the biotechnology industry, where the insertion of foreign genes allows plants to produce pharmaceutical proteins and chemicals. By inserting human or animal genes into certain plants, many scarce and expensive substances may someday be produced in low-cost abundance.

Some examples of successful biopharming attempts include hormones, a contraceptive, a blood clotting agent, blood thinners, industrial enzymes and vaccines. Corn, whose genome has been thoroughly explored, is the most popular choice for biopharming, followed by soybeans, tobacco, canola and rice. According to the 2003 Pew Initiative on Food and Biotechnology, many cutting-edge treatments for arthritis, herpes, cancer and infectious diseases have the potential to be inexpensively manufactured using biopharming.

There are many WSU researchers involved in unraveling the DNA to these kinds of challenges, including several National Academy of Science members: Diter VonWettstein, Department of Crop and Soil Sciences, School of Molecular Biology; Rod Croteau, Institute of Biological Chemistry, and Bud Ryan, Institute of Biological Chemistry. Other active researchers are Maurice Ku, School of Biological Sciences; Vincent Franceschi, director of the School of Biological Sciences, and Mechthild Tegeder, assistant professor, School of Biological Sciences; Kulvinder Gill, Department of Crop and Soil Sciences, and Cornelius Ivory, Department of Chemical Engineering.

Petersen believes the inherent expertise and experience of the WSU research faculty could potentially contribute to other Grand Challenges, especially No. 3 — developing a needle-free delivery system for vaccines. Though this may sound appealing to people in any country, it is especially important to developing countries where the risk of needle contamination and infection is paramount. Along this line, Ku and VonWettstein are already making strides in the field of biopharming — hoping to produce, among other things, edible vaccines.

Edible vaccines may be next Grand Challenge

WSU School of Biological Sciences researcher Maurice Ku and his partners, who have successfully supercharged the photosynthesis and productivity of rice by adding a corn gene, are now collaborating with the University of Tokyo in the development of an edible rice-based vaccine.

This work, said Vice Provost for Research Jim Petersen, could potentially help WSU address Grand Challenge No. 3, one of 14 issued by the Bill & Melinda Gates Foundation to help solve the world’s most daunting health challenges. (Read more about these Grand Challenges and WSU’s work to address Grand Challenge No. 9 on this site and in the Jan. 23, 2004 newspaper issue of WSU Today)

Recently returned from an inaugural meeting with his colleagues in Japan, Ku said, “It was a very positive meeting between the WSU delegation and the University of Tokyo. We are just now getting to know each other’s expertise and capabilities … and the program may be augmented in the future.”

Ku, who will be working on the production side of the project, said that the first edible vaccines would be produced for animals. “This could be extended to people — i.e. for HIV/AIDS — as a future goal,” he said.

Since heat destroys the proteins necessary for effective vaccination, transgenic rice would have to be ground into a powder and added as a dietary supplement for immunization. For developing nations, bananas are targeted as the ideal edible vaccine. Not only would they greatly reduce in-country cost of production and distribution, but they also can be pureed or freeze-dried and are appealing to children. Bananas also would require less intensive refrigeration than conventional vaccines.

Making human collagen in barley

On the other end of campus, Diter VonWettstein, Department of Crop and Soil Sciences, School of Molecular Biology, is quietly revolutionizing the production of barley, that staple of Washington State agriculture and economics. Under a grant from the USDA, he is exploring the use of transgenic barley as a source of safer, higher quality forms of human collagen than can be made from animal byproducts.

There are 26 varieties of collagen in the human body,” said VonWettstein, “and some people, with connective tissue diseases, can’t make them all. When replacement collagen is extracted from animals, you often end up with a mixture of types, which is a problem.”

His goal is to produce a single pure type for medical use. To do this, a specific human gene is added to the barley seed, triggering it to accumulate procollagen (precursor to collagen) as it grows in the field. This is then transformed into collagen during the malting process, a type of controlled germination.

“Safety can be a significant benefit of transgenic manufacturing,” said VonWettstein. “Collagen derived from animal carcasses is used to make commercial gelatin, which is used in everything from cosmetic surgery and plasma replacements to pill capsules, chewing gum and ice cream. This carries the potential for contamination from pathogens such as bovine spongiform encephalopathy (“mad cow disease”) or scrapie, which are very difficult agents to detect and remove from animal tissues.”

Prior to this work in biopharming, VonWettstein, together with research associate Gamini Kannangara, Department of Crop and Soil Sciences, succeeded in engineering barley with a new enzyme that allowed it to be more easily digested by chickens. Barley is not typically fed to chickens as it results in slow growth and sticky droppings. To be used at all for chickens, barley diets require supplementation with cultured enzymes. This new development could be a boon for both Washington chicken and barley growers.

“Washington State produces 40 million broiler chickens annually with imported grain, mostly transgenic corn,” said VonWettstein. “Using barley for raising this number of chickens would require 280,000 tons of normal barley — or one-third of the barley harvest of the state — but only 56 tons of transgenic barley containing the essential enzyme. This transgenic grain could be easily produced on 25 acres of farmland.

Barley also offers the advantage of being able to be grown almost anywhere in Washington State; plus its genome has been very well described, it does not cross-pollinate with other plants and the seed can be stored up to 10 years.”

A meeting of ag and medicine

With the vision inspired by the Grand Challenges together with the collective work progressing throughout Washington State University, Jim Cook is excited about the future.

“We’ll call this the next generation of pharmaceuticals,” said the interim dean of the College of Agricultural, Human and Natural Resource Sciences. “This is about the integration of agriculture and medicine — and at WSU we have a great history in agriculture and knowledge of cropping systems plus the expertise in the College of Veterinary Medicine and the College of Sciences. Downstream we may be able to collaborate with the University of Washington Medical School or Fred Hutchinson Cancer Research Center for clinical trials and evaluation.”

“Yet, this is just the beginning,” Cook said. “We need to lay the groundwork first. We need to communicate across the state — with our legislators, our commodity producers, the farmers and ranchers. We also need the environmentalists to think about it. And we need to provide expertise at the agronomy or herdsman level.

“We want to assure the public that WSU does have the expertise to help in the field as well as the lab…while also assuring safety to the environment and the people. This is long-term research development — we’re looking at 20 or 30 years into the future. But imagine … WSU could be leading it.”

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List below not found in printed edition of WSU Today

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14 Leading Challenges to Global Health

The Grand Challenges, associated with seven broad goals, include:

Improve Childhood Vaccines:

1. Create effective single-dose vaccines that can be used soon after birth.

2. Prepare vaccines that do not require refrigeration.

3. Develop needle-free delivery systems for vaccines.

Create New Vaccines:

4. Devise reliable tests in model systems to evaluate live attenuated vaccines.

5. Solve how to design antigens for effective, protective immunity.

6. Learn which immunological responses provide protective immunity.

Control Insects that Transmit Agents of Disease:

7. Develop a genetic strategy to deplete or incapacitate a disease-transmitting insect population.

8. Develop a chemical strategy to deplete or incapacitate a disease-transmitting insect population.

Improve Nutrition to Promote Health:

9. Create a full range of optimal, bioavailable nutrients in a single staple plant species.

Improve Drug Treatment of Infectious Diseases:

10. Discover drugs and delivery systems that minimize the likelihood of drug resistant microorganisms.

Cure Latent and Chronic Infections:

11. Create therapies that can cure latent infections.

12. Create immunological methods that can cure chronic infections.

Measure Disease and Health Status Accurately and Economically in Developing Countries:

13. Develop technologies that permit quantitative assessment of population health status.

14. Develop technologies that allow assessment of individuals for multiple conditions or pathogens at point-of-care.

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