The Boston Globe 
August 1, 2000    
 
Harvard-affiliated gene studies in China face federal inquiry  
By Alice Dembner, Globe Staff, 8/1/2000  front page
 
 For researchers hunting the genetic causes of disease, the 1.2 billion 
residents of China offer choice targets. Not only are they numerous, but 
many have lived in isolated villages for generations, making genetic defects 
easier to spot. 
 
However, human research in China is also a minefield. It is extremely 
difficult to get true consent from some rural villagers, who bow to authority 
and cannot read. And the communist government's eugenics policies could 
put individuals with genetically linked diseases at risk of sterilization. 

Now, three Harvard-affiliated institutions are caught in this bind. The 
federal government is investigating research initiatives at the Harvard 
School of Public Health, Brigham and Women's Hospital, and Massachusetts 
Mental Health Research Corp. following a complaint from a former colleague 
about their research practices and whether they put citizens at risk of 
genetic discrimination. 
 
The Harvard-affiliated institutions - which are researching potential 
genetic links to conditions ranging from obesity to schizophrenia - say 
they have adhered to the same rules they use in the United States to protect 
study participants. But ethicists caution that human research in China 
requires special vigilance. 
  
''We're all tied up in knots about the ethics of conducting cross-national 
research, particularly between rich and poor countries and those with 
poor human rights records,'' said Ruth Faden, executive director of the 
bioethics institute at Johns Hopkins University. ''Our current set of 
regulations governing research on human subjects is inadequate.'' 
 
A national commission is developing comprehensive rules for international 
human genetics research. The effort grows out of fears about exploitation 
arising as scientists scour nations from Iceland to India to collect genetic 
samples and medical records. Doctors and ethicists have raised questions 
about forced participation, privacy violations, and profiteering. 
  
Despite the concerns, genetic research in China is booming. China has 
been developing its own industry, with numerous labs, gene sequencing 
centers, and a gene bank of about 50 ethnic groups. It has built
sometimes-strained 
collaborations with foreign scientists and biotech companies. 
 
In 1998, Chinese officials temporarily shut down a collaborative project 
on longevity with Duke University and a German research center after a 
Chinese worker questioned the consent process and others accused researchers 
of robbing the country's genetic legacy. The sampling of 4,100 elderly 
Chinese, partly supported by the US National Institute on Aging, was resumed 
when researchers and the government stipulated that no samples would leave 
the country and evidence was offered that the samples were given voluntarily. 
 
No Chinese have joined in the recent complaint against Harvard, but there 
was an outcry in 1996 following a bad translation of an article about 
a new collaboration between six Chinese medical centers and the Harvard 
Program for Population Genetics in an area where about 200 million Chinese 
live. 
 
Several members of the Chinese Academy of Sciences decried the foreigners' 
efforts, saying they were exploiting China's genetic resources, and one 
Harvard scientist was temporarily blocked from exporting genetic samples. 
China subsequently imposed rules requiring all foreigners to get approval 
before exporting genetic material and to share scientific or financial 
proceeds with the Chinese.  
 
Two Chinese scientists at the academy, who declined to be identified, 
said last week that they remained concerned about foreign violation of 
their intellectual property rights. They said they were unaware of any 
problems with the current Harvard studies or any complaints about forced 
participation. 
 
But Gwendolyn Zahner, a psychiatric epidemiologist, formerly an assistant 
professor at Harvard's school of public health, said that Harvard researchers 
did not comply with US rules and that they took advantage of the social 
and political situation in China. 
 
 ''Cheaper, larger, and faster genetics studies are possible in China only 
because the country has not yet established the legal, environmental, 
workplace, and medical protections afforded to American citizens,'' wrote 
Zahner, who filed a complaint against Harvard with the federal Office 
for Protection from Research Risks, which was recently reconfigured into 
the Office for Human Research Protection.  
 
The 15-page complaint, obtained by the Globe, concerns nearly a dozen 
studies recently concluded or still underway in China that are overseen 
by Dr. Ming T. Tsuang of the Massachusetts Mental Health Research Corp. 
and Harvard Medical School or Dr. Xiping Xu of Brigham and Women's Hospital 
and the Program for Population Genetics at the Harvard School of Public 
Health. One study with no genetic component included in the complaint 
was conducted by Dr. David Christiani of the public health school. 
 
The studies, which involved thousands of Chinese participants, were seeking 
genetic and other causes for ailments including asthma, obesity, miscarriage, 
and schizophrenia, and in all but four cases included collection of blood 
samples for DNA analysis. None of the studies involved potential treatment. 
In each case, the Harvard researchers worked with Chinese collaborators, 
who carried out much of the work. Two studies were funded by Millennium 
Pharmaceuticals of Cambridge, and the remainder by the National Institutes 
of Health. 
 
Zahner questions whether participants, some of whom were illiterate,
willingly 
and knowingly consented or whether they were coerced by the involvement 
of local health officials or small payments offered as reimbursement for 
missed work. She asks whether DNA samples might have slipped into the 
hands of local officials, which could put participants at risk of
discrimination 
or forced sterilization. She asks whether participants might have been 
harmed by the use of unsterilized needles to draw blood and whether the 
review boards at the Massachusetts institutions provided proper oversight. 

As evidence to support the allegations, she cites published studies,
knowledge 
gained while helping review studies at Harvard, and trips to China after 
she left Harvard in 1998 when her contract was not renewed. 
 
The researchers and institutes rebutted the complaint item by item and 
vociferously defended their research practices. 
 
''Any time that any research is done anywhere in the world sanctioned 
by the Harvard School of Public Health, it must meet the standards that 
apply to research in the United States,'' said James Ware, dean for academic 
affairs, in comments echoed by representatives of the other institutions. 
''No research was done without obtaining informed consent, and no people 
were put in harm's way.'' 
 
However, the government is still reviewing the institutions' responses, 
months after they were submitted. And ethicists say the conditions in 
China may result in even the most protective measures being applied unevenly. 

Brigham officials acknowledge that the hospital's oversight committee 
could have benefited from more knowledge of China and delegated too much 
authority early on to a parallel committee in China, which allowed work 
to begin before US approval. Faden, while not familiar with the Harvard 
case, said that in the United States ''most local institutional review 
boards are not well equipped'' to oversee international research. 
 
Although there is growing knowledge and acceptance of Western notions 
of consent among prominent researchers in China, the concept is still 
foreign to average citizens in a nation where collective decision-making 
is the norm and coercive policies are common. ''It's a particular problem 
when you're dealing with illiterate populations and particularly complicated 
science, like genetics,'' said Sophia Gruskin, an assistant professor 
of health and human rights at Harvard. 
 
Potential discrimination based on genetic testing is Zahner's and ethicists' 
greatest concern. Some provinces in China have policies requiring
sterilization 
of individuals with certain genetic conditions, and a national law widely 
seen in the West as a eugenics policy is on the books, although reportedly 
it is not being enforced. 
 
The Harvard researchers say they have been careful to use numerical codes, 
rather than names, to link genetic information with medical records and 
to limit access to the key codes. They say no one in the Chinese government 
has asked for access to those codes, although local public health officials 
and public universities are involved in some of the research. 
 
Boston University medical ethicist George Annas said there is always a 
potential risk unless the code linking names to samples has been destroyed. 
''It's hard to believe there's a firewall between public universities 
and the government,'' he said. ''If there's a code that someone can break, 
it's a problem. China does not have the best human rights record.'' 
 
 However, in May, President Jiang Zemin of China told Science magazine 
that ''the prevention of gene-based discrimination'' and ''the protection 
of privacy'' were ''issues of concern.'' He also said collaborations with 
Harvard were proceeding smoothly. 
 
 This story ran on page A01 of the Boston Globe on 8/1/2000.  
© Copyright 2000 Globe Newspaper Company