Rules outrun by stem cell research
The growing importance of stem-cell research is increasing the need for ethical and other guidelines, reports Science writer Leigh Dayton
REMEMBER Woo Suk Hwang, Korea’s disgraced ‘‘ king of cloning’’? Between February 2004 and November 2005 the scientist’s star rose and blazed in international glory. It ended in tears, of course, after multiple investigations revealed that the King and his colleagues had faked most of the data they published in two breathtaking papers published in the journal Science .
No, the group had not cloned the first human embryo. No, they had not crafted customised embryonic stem (ES) cells from 11 people. The only result from that scientific annus horribilis left standing — and on four legs — was Snuppy the Afghan puppy, the world’s first cloned dog.
The revelations rocked stem cell researchers from Seoul to Sydney, and London to Los Angeles. Why did Hwang do it? How did he get away with it? What can be done to prevent future fraud? And are there other ethical clouds looming on the stem cell horizon?
Such questions are of growing importance as the funding pool for ES cell research deepens. For instance, this week the NSW Government committed $13 million over four years to spinal cord research in its budget statement. Laboratories conducting ES cell work in the area will soon be able to apply.
The questions are of particular significance to Korean-American philosopher and bioethicist Insoo Hyun of Case Western Reserve University in Cleveland, Ohio. Hyun had spent the summer of 2005 in Hwang’s laboratory — at the pinnacle of the group’s fame— studying the ethical, legal and cultural dimensions of human therapeutic cloning, also known as somatic cell nuclear transfer, or SCNT. Hyun claims he didn’t see it coming.
‘‘ The news was devastating for me personally when I found out the research was fabricated,’’ says Hyun, in Australia for this week’s annual meeting of the International Society for Stem Cell Research (ISSCR) in Cairns, and to meet Australian scientists and ethicists at the behest of the Australian Stem Cell Centre (ASCC) in Melbourne and the Menzies Foundation. ‘‘ I was extremely shocked, to say the least.’’ To this day, Hyun’s not certain why Hwang did it. He’s not even sure Hwang acted alone. While he condemns Hwang’s deceit as ‘‘ unforgivable’’, Hyun says the roots of the fraud lie in the complexity of the new field of ES cell research. ‘‘ Society sets up the crime and the criminal commits it,’’ he says.
For starters, as stem cell scientist Megan Munsie notes, no research group can tackle big ES cell projects alone. ‘‘ The skill sets required to do nuclear transfer, ES cell derivation and cloning are (specialised),’’ says Munsie, ASCC director of scientific affairs and policy.
Little wonder, then, that biomedical researchers such as Sung-il Roh of Seoul’s MizMedi Hospital encouraged Hwang to join them. As a veterinary researcher Hwang had successfully cloned farm animals. If cows and pigs, why not people? A large collaboration was established and the Hospital and Seoul National University groups got to work.
‘‘ There were over 40 people involved in the Hwang team. I don’t know how many at the MizMedi team,’’ says Hyun. ‘‘ There was very bad co-ordination and lack of oversight over the entire research team.’’
He adds that government regulations were made on the run to keep up with the results apparently pouring out of Hwang’s lab.
For Hyun, good regulation, oversight and ethical rules — governance — might have prevented the scandal. It’s also the best way to reduce future fraud. Further, he believes proper governance will enhance scientific collaboration, producing better and faster results, and give researchers and the public confidence that fraudsters will be caught.
That’s crucial in prominent fields like ES cell research, claims Australian-born molecular and cell biologist Elizabeth Blackburn, now with the University of California at San Francisco. ‘‘ Having the settings [right] will be the key to making some of these problems less likely to happen,’’ says Blackburn, who sat on the US President’s Bioethics Council until she blew the whistle on government misrepresentation of science.
Governance is also linked to debates about the potential of stem cell research to deliver new treatments for conditions such as Parkinson’s disease and spinal cord injury, claims Blackburn. That’s so since ‘‘ oversimplified’’ allegations from opponents can push equally oversimplified claims from proponents. ‘‘ The terrible problems of the [ Hwang] fraud were fuelled in part by enormous [public] expectations which grew out of the polarisation of debate,’’ she says. ‘‘ This is not a good way to get good science done.’’
Leading experts couldn’t agree more. Yet setting regional, national and international rules that fit together is enormously difficult. Just getting off the starting blocks can be tough. While scientists in countries such as China and Singapore have no restrictions on SCNT, and those in Britain have tight regulations allowing it, their counterparts in Australia and the US weather ongoing storms over any use of embryos, cloned or not.
The intensity of Australia’s storms was felt in 2002. That’s when federal Parliament debated and passed the nation’s first legislation permitting and regulating stem cell and embryo research, while banning reproductive or therapeutic cloning. The Lockhart Review reassessed the laws and in 2005 recommended changes to tighten and clarify governance. Controversially, one of the 54 recommendations called for legalisation of SCNT.
After heated debate involving ‘‘ oversimplified’’ claims that SCNT was the slippery slope to animal-human hybrids, the technique was allowed and this month the revised national laws came into force. Already Victoria has passed legislation enabling the national laws, NSW has begun the process, and WA and Queensland are expected to do so soon.
In contrast, Marianne Horn — a nurse, lawyer and head of the US state of Connecticut’s research and development office — says US scientists work in legislative limbo. There’s no national framework regulating ES cell science, so 11 states, including Connecticut and California, have legalised it. To help simplify matters, Horn has spearheaded efforts to find common legislative ground. ‘‘ We want an understanding so different standards don’t get in the way of sharing research [nationally and internationally].’’
To get the governance ball rolling, the USbased ISSCR has released the first guidelines on human ES cell research. According to Hyun, who chairs the ISCCR ethics committee which produced the guidelines, they’re not legally binding. But they do carry the weight of scientific opinion and provide a starting point for establishing regulations that will encourage international co-operation yet respect regional scientific and cultural traditions.
‘‘ It’s not going to be sorted out overnight,’’ says Hyun. ‘‘ But I’m hoping ISCCR will be the central clearing house for policy.’’
A plank of any policy, Hyun suggests, involves the informed consent of people donating eggs or cells for research. In Australia human eggs — for now, an essential ingredient of SCNT— can only be donated by IVF couples who do not need them. There is no question, like elsewhere, that non-IVF women should be paid to donate them.
While Hyun says it’s important to nut out regional details of egg donation, he says no jurisdiction has dealt with the ‘‘ coming cloud’’. It is, he warns, the seemingly innocuous practice of donating ‘‘ somatic’’ cells, ordinary cells like skin or muscle cells. These cells will always be the main SCNT ingredient because scientists want to clone ES cells from them to study the molecular underpinnings of diseases such as Alzheimer’s or multiple sclerosis.
Because experts also hope ultimately to tailor treatments for such conditions for individual people from their personal cells, Hyun fears teams will be flooded with potential donors, eager to be first in line for possible therapies for themselves or their disease group. He fears people will give their consent without fully understanding implications, such as the fact they’ll be monitored for life or that personal details and cells may be shared between groups.
After all, back when it looked like Hwang had the goods, 3500 people filled in online donation forms in one hour. ‘‘ There was a frenzy,’’ Hyun says. ‘‘ It was amazing to me.’’
Thankfully, Hwang’s fraud was detected, in part by revelations that eggs were being donated unethically, and in part by the inherent scepticism of scientists trawling over his extraordinary claims. The upside to the ruckus is that scientists and regulators are getting their acts together.
‘‘ Things have moved on,’’ says Blackburn. So too has Hwang. Fired from the university, last year he opened a privately funded lab focusing on cross-species organ transplants. And you can bet Korean regulators are keeping a close watch, a very close watch.
Hyun: Had no inkling he was watching a fraud of international proportions