We are all used to reading about tension and controversy between China and the United States. It seems a product made in China is recalled almost every day. Then there are disputes over intellectual property rights, and trouble over human rights, Taiwan and Tibet. The list goes on and on. Success stories tend to get less attention, even if they bring results that help alleviate human misery. This is one such story. Medical researchers from China and the U.S. have made quiet but notable progress in eliminating a range of particularly debilitating birth defects: spina bifida and other related congenital problems, which are known as neural tube defects.
This is a story that has unfolded over a quarter century, and it holds lessons for anyone from the outside who wants to deal successfully with China.
“WhenWhen you want something to happen, you cannot give up. You need patience. So many foreigners come to China and think they can have a success because they have made contact once or twice. Nothing happens based on one meeting.”— Dr. Li Zhu
The China-U.S. Collaborative Project for Neural Tube Defect Prevention, under the auspices of the Beijing Medical University (BMU) and the U.S. Centers for Disease Control and Prevention (CDC), has achieved both scientific and operational success. First, the rate of neural tube defects in the Project sites in the high-risk northern provinces dropped 85 percent among the women who were at least 80 percent compliant in taking supplements containing a vitamin called folic acid. Even among women in the low-risk southern provinces, supplementation cut the rate by 40 percent. Second, the research team collected complete and clean data on 247,831 women and their pregnancies over the three years of the community intervention program. Forms were completed for 70 percent of the infants within one week of delivery and for all but a few percent within three months. With these numbers, the project became perhaps the largest community intervention study ever conducted, studying more than a quarter of a million women and their babies and relying on more than 16,000 health workers across 30 local counties and cities in five provinces. The rate of women lost-to-follow-up (5 percent) fell far below levels generally expected for studies of any kind. The collaborative project generated several notable articles, with the landmark study published in The New England Journal of Medicine.
The groundwork for the Project was forged in 1983, when a BMU professor of obstetrics and gynecology, Dr. Yan Renying, feared that too many babies were dying in Shunyi County, a suburb of Beijing. She requested technical assistance from the World Health Organization to guide her and her colleagues in conducting surveillance on infant deaths. WHO sent an epidemiologist who was on loan from the CDC: Dr. Brian McCarthy. He conducted several workshops so the clinicians and professors could learn the fundamentals of field and perinatal epidemiology.
One third of the deaths were due to neural tube defects, including conditions such as spina bifida. The incidence of the defects was 7.3 per 1,000 births. Dr. McCarthy wrote at the time, “To the writer’s knowledge, this is the highest in the world and does not even represent the highest in the Beijing area.” In one of Shunyi’s townships, the rate of newborns born with any form of neural tube defect was astounding and tragic: Nearly 17 of every thousand infants had one of the defects—the highest in the world.
Standing in the dirt near their pig pen, the solemn-faced Chinese grandparents explain that the parents of a four-month old baby girl with spina bifida have gone away. Her mother has run away, overcome with grief after having a child with a birth defect. Her father is out searching for his wife. The grandparents have not heard from them, and the baby still has no name. The moment is captured in a photograph that quickly and deeply tells the story of spina bifida and related birth defects in China.
—McKimmie M. China’s acid test. The West Australian, June 25, 1994:1-2.
Neural tube defects pose a grave public health problem everywhere in the world, but they are particularly prevalent in many parts of China. Affluent nations such as the United States can provide surgical, medical, and physical therapy to help afflicted infants survive and eventually lead productive lives. Unfortunately, poorer nations such as China lack these therapeutic services. That lack of services, along with the strain on the families’ finances, dooms these infants to early death, and frequently death while in utero. Their mothers and fathers suffer not only the loss of a pregnancy or child, but the ones who have a baby with the defect also bear a social stigma.
In 1983, Dr. Yan reported the findings to the public health world in the first annual Europe-China conference on perinatal health. At Dr. McCarthy’s urging, Dr. Godfrey Oakley, CDC’s director of the Birth Defects Branch, attended the conference. After hearing Dr. Yan’s presentation and looking over hospital logbooks that recorded infant deaths, Dr. Oakley pronounced, “China may have an epidemic of neural tube defects.” Dr. Oakley had long been interested in finding ways to prevent spina bifida. At the time, the average cost for medical and surgical care for the surviving children born with spina bifida approached $100 million [US]. If the other costs of caring for these children are added, the total grew to $800 million. The heartache could not be put into monetary terms.
A substantial part of the difficulty in preventing spina bifida and similar defects was that the nervous system develops within a month after conception, before many women know they are pregnant. The other part of the difficulty was that medical researchers did not know what caused the defect. Was there something unusual about the women who lost pregnancies or delivered dead or deformed infants? Had any unusual event taken place that could have exposed the mothers and their fetuses to toxins? Did affected families pass on inherited problems? During the 1960s and 1970s, epidemiologists were just beginning to gather a body of evidence about the causes of birth defects. They suspected that some might be due to genetic abnormalities, but it would be three decades before the human genome project would produce enough information to give people hope of finding genetic keys to birth defects.
Dr. Oakley and his CDC colleagues were intrigued by the suggestion from earlier observations that vitamin deficiency might be involved, and had for several years been trying to find funding for a definitive clinical trial to look at the issue. Although CDC had great interest in finding effective ways to reduce the number of babies born with the condition, there were obvious barriers to launching a definitive clinical trial in the United States. Very small numbers of potential study cases meant it would take a decade or longer to find statistical significance; the costs of running a rigorous scientific study were high and growing higher; and it would be difficult to find comparison (control) cases among a population of women, who, upon hearing media reports of the study, could easily buy multivitamins on their own.
China, on the other hand, could provide a venue where a trial could be conducted at far lower cost and over a far shorter period of time, given the exceedingly high rate of neural tube defects. About one quarter of all such defects in the world were in China. China needed to manage its epidemic of neural tube defects, but it also sought to step boldly and rapidly into the modern age of science and technology. Together, Dr. Oakley and Dr. Yan agreed to work on a proposal that their two institutions join the search for ways to prevent these most common birth defects. It would take eight years of persuading superiors, finding funding, and calming the political suspicions, but eventually the collaborative project turned from proposal to reality.
At first, the project had all the ingredients for failure. The U.S. researchers were uncertain about the ability of the Chinese to conduct the rigorous trials that were coming to inform evidence-based medicine. In the early 1980s, the Chinese scientific community was just emerging from the effect of the national policies that closed them off from the rest of the world, causing their methodologies to lag behind their Western counterparts. Countless health professionals had been sent to rural outskirts during the Cultural Revolution, and the foundation of expertise remained thin even in the later 1980s when a fledgling project office housed at Beijing Medical University needed to find young epidemiologists, who had to learn many of their skills on the job.
In Atlanta, a CDC team faced the problem of how to coordinate massive fieldwork thousands of miles away. Tanks rolled into Tiananmen Square; for months, the Project appeared to be in jeopardy of termination. Some years later, U.S. jets mistakenly dropped bombs on the Chinese embassy in Belgrade, making the Chinese fear for the safety of U.S. researchers assigned to live in Beijing. The principal investigators in the BMU office faced pressures from mayors in the project counties, who pressed to get more of the tight research money as they pondered how they could produce the expected work with a shortfall of resources. The list of obstacles went on. China lacked telephones and electronic systems. Roads were bad. Education levels were low among the families who were to participate in the study. Delays took months, and sometimes years.
Managing the details in the field were two young epidemiologists: BMU’s Dr. Li Zhu and CDC’s Dr. Robert J. Berry. They shared a belief in what they felt were the critical underpinnings that allowed the Project’s success: the right person in the right place; perseverance despite the obstacles; relationships developed over “walking a thousand miles” together; and sheer human capital.
The first principle of success was finding the ‘right’ people who knew how to build relationships, had drive, and shared a common work ethic. Every project needs a pivot point, someone who connects all the pieces. Dr. Li Zhu filled that role, linking Ministers of Health, university administrators, CDC researchers and chiefs, provincial and city and county leaders, medical directors, and staff. The American team, too, had some of the ‘right people’ who invested substantial time and effort. McCarthy, Oakley, and other CDC epidemiologists made dozens of visits to China. Dr. Berry and later Dr. Jacquelyn Gindler pulled up their households and lived in Beijing for several years, supervising the details of the Project’s logistics and learning Chinese so that they could communicate directly with their colleagues.
Perseverance was the second reason for success. “When you want something to happen, you cannot give up. You need patience,” Li Zhu explained.
“Think about it. We were successful because a lot of people went to the United States, and a lot of Americans came here. We had meeting after meeting. We worked together a long time, sometimes not knowing what would come of it. It has nothing to do with theories. You cannot find this kind of ‘theory’ in a book. If you want to do anything, you need to keep trying. Be patient, but insist that decisions be made. Chinese and Americans both talk about ‘gritting your teeth.’ You have to want to do what it is necessary for what you want, no matter how hard, no matter the difficulties and obstacles.”
The third underpinning of success was found in “friendships,” both personal and professional, forged over years of detailed work. In building personal relationships, each team earned trust and learned to be trusting; respected each other’s wisdom; and shared ownership not only of achievements, but also of frustrations. Everyone worked on working together. Berry reflected, “I think all the other relationships between bureaucracies and cultures are probably much less important than personal relationships. I didn’t really understand that well when I went there.”
The Project was a model for successful teamwork not only between professionals, but also between scientists and government officials. The research was supported by the government and conducted by the scientists. “During the long-term collaboration,” said Dr. Li Zhu, “we faced a lot of problems and difficulties and obstacles. We always got together to discuss these challenges and think about solutions. I then talked with the Ministry of Health to find a solution from the China side and explained what I thought was the situation in the United States. My CDC colleagues worked on the U.S. side, and they could explain the Chinese situation.”
Dr. Berry agreed. “From the beginning, we had the ability to sit down and decide what to do and, based on science, decide what should be done. The Chinese would get together and, because they were experienced within their own system, they did what needed to be done on their side. We did the same on our side.”
Human capital came from the thousands of health workers throughout all levels of the health care system: hospital workers, clinic staff, registration officials, doctors, nurses, technicians, data-entry clerks, secretaries, drivers, and community service workers. A common opinion in the West is that developing countries, with workers who may have less training and little monetary reward for the added burden, cannot attain the accuracy and follow-up rates achieved in developed nations. However, no one had informed the young investigators, Drs. Li Zhu and Berry, that these were accepted limitations; instead, they sought the highest level of precise, accurate, and useful data.
“One of the things that really made this Project work,” said Dr. Berry, “was that the counties were so engaged. In the beginning, little of what we were doing made sense to them, but we sent reports back to the counties to help them fix problems and it got people engaged in collecting data and making the data good.” Local health officials traveled to their village clinics and township hospitals to track down information missing from the original data-collection booklets and forms. They kneeled over giant cross-tabulation tables laid across the floors of their offices to begin the detective work of finding the right matches, sometimes working most of the night. They worked on the floor, because that was the only space large enough to spread out one million surveillance cards.
As the Project achieved its stated goal to prevent spina bifida, it additionally achieved others. BMU developed institutional strength by fostering young, bright, hardworking scientists. The local Project sites grew capacity through the training and experience, expanding the expertise beyond the study’s needs and into the realm of medical-care delivery and other types of medical research. The Project developed one of the largest databases in the world, which grows as the researchers continue to follow more than 200,000 families each year. The data collected are clean and complete; they are cited throughout the world. The surveillance system can track the potential long-term benefits from exposure to folic acid, of course, but in these records of mothers and children lie any number of answers for questions no one has yet thought to ask.