Thai Biologist Strikes Blow Against Malaria

Malaria - the World Health Organisation's top priority tropical disease, killing two to three million per year - has met a new match: an unassuming, soft-spoken Thai biologist.

Yongyuth Yuthavong is chief of the protein study group of the National Centre for Genetic Engineering and Biotechnology (Biotec). After devoting more than 30 years to molecular research, he finally made a breakthrough in his fight against the malaria parasite.

The 59-year-old Oxford-educated scientist and his team have recently succeeded in discovering the structure of the malaria parasite's enzyme, called DHFR, which causes the parasite to resist drugs. The discovery will lead to new directions in designing effective anti-malarial drugs directly targeted at the enzyme.

While the discovery received accolades from a world famous journal of biology, Nature Structural Biology, which devoted nine pages of its May issue to the breakthrough, the reception of the news in Thailand has generally been muted.

Malaria is caused by a parasite carried by the anopheles mosquito, and human beings have been fighting against it for a long time. The malaria parasite has been a perennial winner. Whatever weapons humans developed to combat it, the parasite always fought back successfully.

The pesticide DDT was developed and used worldwide, but the tiny insect developed a tolerance. Anti-malarial drugs, even the most effective like antifolate, were developed to directly attack the parasite, but it mutated to resist them.

Worldwide, 500 million people are afflicted by the disease, which causes millions of deaths each year. Scientists believe that if the parasite lost its capacity to mutate, the death ratio would be drastically reduced.

According to Yongyuth, the most important obstacle in the fight against malaria was that no one knew the structure of the parasite before mutation. Thus effective drugs to limit the ability of the parasite to mutate could not be designed.

The key factor that launched Yongyuth and his team on their breakthrough was when they were able to crystallise the pre-mutated enzyme DHFR then study the way in which the crystal interacted with X-rays. The three crystal structures of the enzyme are also presented in the Nature Structural Biology article.

Yongyuth's discovery of the structure of the pre-mutated version of the DHFR enzyme of the parasite sparked hope in scientists worldwide to develop a new set of weapons to combat malaria.

The National Centre for Genetic Engineering and Biotechnology (Biotec) is now in the process of negotiating with leading international pharmaceutical companies to collaborate in developing a new generation of anti-malarial drugs by using the discovery of Yongyuth and his team.

Yongyuth admits that the process of crystallising the enzyme might not have succeeded without close collaboration from his colleagues. Besides structural chemists and molecular biologists from Biotec and leading universities including Chulalongkorn and Mahidol, he also received collaboration from his old pals at the University of Edinburgh led by Malcolm Walkinshaw.

"The discovery is the biggest thing in my life as a scientist," he said proudly.

Born in 1944, Yongyuth chose not to join the military as had his father and two older brothers. After high school, he intended to be a doctor. However, after two years in Mahidol pre-medical school (now university), he became aware that medical science was not his preference. His interest switched to chemistry. He received a scholarship from the Thai government to study at the University of London, where he obtained a bachelor's degree in chemistry.

He then gained a doctoral degree in organic chemistry from Oxford University in 1969 and was appointed professor of Biochemistry in 1983 by Mahidol University, where he made his teaching career.

Yongyuth, married with two children, has committed himself to fight the malaria parasite ever since he conducted post-doctorate research at the University of California, Los Angeles, in 1973-1975 - a time when the emergence of resistance to most anti-malarial drugs was first reported. The ultimate goal of developing a new generation of anti-malarial drugs has been on his mind since then. He started his career as a full-time researcher to work on the development of anti-malarial drugs at Biotec in 1998.

"Malaria is a tropical disease. There is no incentive for big pharmaceutical companies to invest in developing drugs to combat the disease since the epidemic is only reported in poor countries in the tropical zone. In terms of economical returns, it is not worth investing in," he says bitterly.

However, through three decades of research into the malaria parasite, Yongyuth has received financial support from several Western aid organisations including the Medicines for Malaria Venture, which financed the last three-year project during which Yongyuth made his breakthrough. Other financial sponsors are the European Union, the Wellcome Trust and the Thailand Tropical Disease Research Programme.

Deep engagement in malaria-parasite research has brought Yongyuth to the forefront among regional scientists. He was awarded "Outstanding Scientist of Thailand" by the Foundation for the Promotion of Science and Technology in 1984 and was also recognised by the Asean Committee on Science and Technology with the award for "Asean Science and Technology Meritorious Service" in 1998.