http://www.chinadaily.com.cn/cndy/2012-12/12/content_16008316.htm

One man's commitment points the way to a brighter future for some patients who may otherwise lose hope, and it's all thanks to the animals he has so carefully nurtured in a little village in China. Liu Zhihua and Feng Zhiwei describe the breakthrough.

These pigs are very famous, and very precious. Their fur is sleek and silky and they nuzzle their feed while listening to music playing in the background. They are China's first donor pigs bred for inter-species transplantation research, and their fame has spread beyond China, throughout the international medical community.

They live in a village two hours' drive from Changsha in Hunan province. It's the first breeding center for donor pigs in Asia and only the second in the world.

"Having a center to raise donor pigs at a large scale is important for research, as now we have a steady donor pig source," says Wang Wei, who is the prime initiator of the breeding center officially commissioned in August.

Wang, 52, is the director of the radiology department of the No 3 Xiangya Hospital of Central South University in Hunan.

The setting up of the breeding center is the achievement for his team and the world in more than 10 years of research in inter-species transplantation - using animal organs or tissues in humans.

Wang started research in 1995, after he read a paper on the subject. He was enthralled.

"Inter-species transplantation has huge potential for improving fatal and chronic diseases, such as diabetes, because of the shortage of human organs for clinical implants," Wang says.

He says he wanted something beyond radiology - something more innovative and groundbreaking.

"I was young and brave. If I were to choose again, I probably would not have the courage to make the same choice."

Scientists in the United States had already established that pigs were better donors for human transplants than any other animal.

Wang's first goal was the implantation of pigs' hormone-producing islet cells, a procedure that will help cure Type 1 diabetics.

This procedure would make use of his expertise in radiology and interventional treatment. But the human body's immune response or a rejection of pig organs or cells meant he had to find ways to reduce the rejection while keeping the recipient patient's ability to defend his body against other infections.

Also, not every pig can be a donor.

Donor pigs must be free from viruses and bacteria that are known to infect humans. The solution is to selectively breed, or genetically modify, the animals.

Wang chose to breed the pigs instead of meddling with their genes. He had no prior knowledge of, or equipment for, inter-species transplantation research, so he taught himself through reading all he could find.

He had to figure out what equipment to use and what kind of experiments to conduct, Wang says.

His first batch of anti-immunity medication was donated by a drug company. In 1996, the hospital gave his laboratory 100,000 yuan ($16,000), which he used to buy basic equipment, such as microscopes and purification devices.

"I was kind of single-minded," Wang says. "I would try all ways to overcome the difficulties, but I never thought of giving up."

In 1998, he experimented with a new way to implant pig islet cells into monkeys through the hepatic artery and got support from the National Fund for Nature.

The trials on the monkeys proved that his new approach was safer and more efficient than the previous traditional method of implanting through the hepatic portal vein, which was widely used all over the world.

Wang announced his research results at the 7th Annual Meeting of International Pancreas and Islet Transplant Association in 1999 in Sydney, Australia. That success became his ticket to international fame and more opportunities to attend international academic meetings.

The same year, he applied to the Ministry of Health for approval for testing the procedure on humans, and got permission.

From 2000-04, he led the tests on human subjects, involving 22 Type 1 diabetic volunteers in the first such experiment in the world. His team transplanted processed pig islet cells into 20 patients once, and two patients twice, through the hepatic artery.

Wang's team recorded the physiological data. They monitored for contraindications, as the islet cells stayed effective in different patients for different lengths of time, with the help of anti-immunity drugs. There were no serious or uncontrollable side effects. The team noted a slight difference in rejection among Chinese and Caucasian subjects.

In 2005, Wang again published his research at the 9th annual meeting of IPITA in Switzerland. This time, his work was so distinguished that he was able to invite celebrated researchers in the field to his breeding center in Changsha.

Among them was Carl-Gustav Groth, a former judge for the Nobel Prize in Physiology or Medicine. Groth described Wang's work as "pioneering".

In the meantime, Wang was searching for pedigreed animals to breed. The purer its pedigree, the easier it is to keep the pig's most desirable features, Wang explains.

He wanted pigs that did not harbor human disease agents in, or on, their bodies.

More importantly, each pig had to have a strong pancreas for the islet cells.

After 14 attempts, he finally succeeded in breeding the right pigs for the human experiments. In 2007, Wang obtained the plans of the world's first donor pig breeding center in the US state of Minnesota.

He improved the design for his own use and built the breeding center in a suburb of Changsha.

In August this year, the breeding center was officially commissioned.

The breeding center cost more than 60 million yuan ($9.64 million). It has climate-controlled and sterile facilities, a waste-disposal system and even a sound system that plays music for the pigs.

"The center is a solid base for clinical research," says Yi Shounan, an immunity and transplantation specialist with the University of Sydney. "What Wang has achieved is very encouraging for inter-species transplantation researchers."

Yi is in China to explore cooperation opportunities with Wang's university, the Central South University in Changsha.

But Wang has no idea when he will start the clinical research.

In 2005, the World Health Organization established a list of strict preconditions before human clinical research can be conducted. The list includes requirements for a donor pigs cultivation center, trials on primates and research specifications made by medical authorities and associations.

"The human tests we did before 2005 were approved by the ministry, and legal at that time," Wang says. "But under the current WHO requirements, we will not be able to do it again in the immediate future."

There are also other considerations about inter-species transplantation apart from the strict regulations on clinical tests.

In China, and other parts of the world, certain ethnic or religious taboos will not allow patients to use cells or organs from pigs. For example, the Hui ethnic group, who are Muslims, do not eat or even touch pork, so using islet cells from pigs is out of the question.

Worldwide, animal rights groups also oppose the research and practice. And some medical experts are afraid that, in the long term, these transplants may affect human genetics - or the organs may harbor dangerous disease agents that may not have been identified.

Contact the writers at liuzhihua@chinadaily.com.cn and fengzhiwei@chinadaily.com.cn.

(China Daily 12/12/2012 page19)