The promise of stem cells

Ruth Beran finds that few people want to stick their necks out when it comes to touting the benefits of stem cell research.

Can stem cells deliver on their promise? That was the question put to five leading stem cell scientists and ethicists at a symposium held this month by the Victorian Infertility Treatment Authority.

The overwhelming message from the speakers was that while stem cells are likely to deliver results some time in the future, there needs to be caution when making promises.

"There's promise and there are promises," said Australian Stem Cell Centre CEO Dr Hugh Niall. "There is obviously a wide difference between the two. Promises are close to, or bordering on, guarantees. We have to be very careful about what we promise, and that will determine whether in fact we can deliver on the promises."

Dr Elizabeth Finkel, author of the book Stem Cells: controversy at the frontiers of science, told delegates that: "Stem cells are going to deliver for sure. But if you ask me what the winners are going to be, I wouldn't dare tell you right now."

While Finkel was reluctant to predict the raft of advances that may result from the stem cells technology platform, she listed some examples of what she saw as the "low hanging fruit". These include the production of blood cells, insulin producing cells, bone marrow cells for heart disease repair, and brain cells for Parkinson's disease.

First things first

But Dr David Edgar, scientific director of Melbourne IVF and Reproductive Services at the Royal Women's Hospital, said the real question being asked at the symposium was not whether stem cells can deliver, but what contribution human embryonic stem cells can make in the form of propagating cell lines in the laboratory. "That's a very different thing," he said.

"Most of us in the practice of IVF know that embryonic stem cells can deliver on their promise -- they do it every day. The embryonic stem cells present in the embryo can go on to form something as complex as an adult human being."

Edgar said the most important promise of human embryonic stem cells is the ability to improve our understanding of the process involved in normal and abnormal human development. "Nothing can flow until that is mastered," he said.

Without an understanding of the key regulatory pathways that turn a primary embryonic stem cell into other types of cells, scientists will be "stabbing in the dark" if they move onto stem-cell-based therapies, said Edgar.

"To jump to the later promises before we've actually fulfilled the earlier ones runs the risk of making very grave mistakes in this area," he said.

And having seen how careful systematic knowledge has led to the rational design of new culture medium which in turn has increased the probability of IVF embryos surviving, Edgar is convinced that this type of process does not happen "magically".

Once this basic understanding of developmental processes has been reached, stem cell research could then be used to provide model systems for developing novel pharmaceuticals, he said.

Hurdles and obstacles

Edgar then referred to two controversial areas of cell-based therapies, the transplantation of embryonic stem cells derived from excess human embryos and the generation of embryonic stem cells for specific individuals.

Both areas are fraught with potential obstacles, issues that were also referred to by the other speakers. "There is an inherent tendency of a cell culture maintained over time to drift in the direction of cancer," said Niall.

While a lot of progress is being made to reduce the level of genetic instability in stem cells, Niall said that "nevertheless it is a major issue".

Researchers are also having troubles training human embryonic stem cells to make specific cells such as dopamine neurons, said Finkel, although they have had success with mouse embryonic stem cells.

"Bear in mind we've had mouse embryonic stem cells now for 24 years," she said. "We've had human embryonic stem cells for seven."

There are also legislative and regulatory obstacles to be overcome. "The biggest legislative challenge," said Edgar, "is whether the current federal legislation can shift in such a way to allow what's effectively viewed under the current legislation as the creation of human embryos for research."

In particular, federal legislation currently prohibits research on embryos generated by somatic cell nuclear transfer. Somatic cell nuclear transfer (SCNT) is the process whereby an embryo is created by removing the nucleus of an egg and replacing it with the nucleus of a donor somatic cell.

SCNT can be used to create patient specific stem cell lines or disease specific stem cell lines, said Niall.

A committee, chaired by retired Federal Court judge John Lockhart, has recently wrapped up its review of Australia's federal stem cell legislation, the Research Involving Human Embryos Act 2002 and the Prohibition of Human Cloning Act 2002, and "the outcome of this review will be very important in setting the scene for embryonic stem cell research going forward," said Niall.

Availability is another hurdle to the promise of stem cells, said Edgar. "There's no shortage of patients who have excess human IVF embryos who are willing to donate those embryos to research, if they can identify with particular areas. Stem cells research is certainly one of those areas," he said.

"The question is, what number do we need to be able to achieve the ends and how efficiently can we actually generate those lines?"

Other issues that need to be considered are safety and risk, said Edgar, and producing stem cells as therapies will involve authorities such as the US FDA or Australian TGA. "Those of us involved in IVF know some of the hoops we've had to jump through in the last decade just to be able to use culture medium that we've used to culture IVF embryos permanently in our practice," he said.

Niall also raised this issue when he talked about genetic mutations and instability, particularly when manufacturing large numbers of cells. The cells produced will need to be sufficiently well defined for the FDA or TGA to approve before they can be injected back into a patient. "How guaranteed is it that 100 per cent of those cells will go down that pathway and remain on that pathway?" asked Edgar.

Tailored to fit?

Edgar said that it has always "intrigued" him that the rationale behind therapeutic cloning (or SCNT) is that tailored stem cells are produced to treat an individual. "Can we really exclude the possibility that all we're doing is giving them back the same genome which has resulted in their disease?" he asked.

While Niall acknowledged that there are hurdles to overcome in relation to stem cells, he said, "these are not absolute hurdles."

"It may well be that for life threatening conditions, it's possible that this sort of technology will develop and be used sooner rather than later," he said. "Sooner is probably quite a few years, but there are some trials going on at the moment with stem cells to treat diseases. Heart failure is one."

Finkel also referred to these trials, particularly work being conducted by Prof Silviu Itescu, the chief scientist of Melbourne-based company Mesoblast.

"His message is good placebo controlled trials is what we need to get this into the realm of evidence based medicine," said Finkel.

'False debate'

Niall said the polarised debate about embryonic stem cell research versus adult stem cell research was "a false debate".

"There has been hype and a lack of clarity in explaining the science in both of these areas," he said. "Both are needed. It is not 'either/or' from a scientific point of view. We have so far to go in this field, we need all the insight we can get from studying embryonic stem cells and adult stem cells."

Finkel voiced a similar opinion. "Anybody who has done research knows that there are swings and roundabouts. Glib statements that say you can pick and choose don't deserve to be dignified with a response."

Replicant armies

Senior research fellow Dr Neil Levy from the University of Melbourne's Centre for Applied Philosophy and Public Ethics said there needs to be caution in making promises about stem cells, and used the example of a recent Time CNN survey which found that 98 per cent of Americans polled opposed reproductive cloning.

"That's not an interesting result, because you get that every time," he said.

However, 22 per cent gave their primary reason for opposing reproductive cloning as "it could be used to create an army of mindless replicant soldiers", said Levy.

This lack of biological knowledge concerned Levy because "If you ask people to make a decision and they've got no idea what you're talking about, then you might as well roll a dice."

Levy is an advocate of democratic control of science which in turn requires an informed public. A "big worry", according to Levy, is "science by press release" because it undermines the ability of people to make informed decisions.

"When scientists and those with vested interests (even scientists whose work they promote) claim they are able to produce results tomorrow and the day after -- or the results normally produced by adult stem cells can all be produced by embryonic stem cells -- they're just making claims that there isn't evidence for," said Levy.

"This is a technological platform and we can be sure that it's going to produce results but we can't really be sure what the results are and we can't be sure how long it's going to take," he said. "That's what we can say with a great deal of confidence."

Levy blamed the public's unrealistic image of science on a vicious circle, where bad education encourages people to vote for governments who don't prioritise science education. This leads to bad media reporting, which encourages scientists to engage in 'science by press release'. This in turn leads to people voting for bad governments that don't encourage science.

However, Levy is said the vicious circle could be turned into a virtuous cycle. "If we have an educated public -- educated about science -- they will demand better science reporting," said Levy. "Journalists will be better educated themselves. Scientists will have incentives to report their results more cautiously, more soberly, and more realistically. The educated public will demand that their governments fund scientists better and fund science education better."

Ethical barrier

Dr Robert Sparrow, a philosopher at Monash University's Centre for Human Bioethics concluded the symposium by arguing that there is an unrecognised ethical barrier to realising the promise of stem cell therapies based on therapeutic cloning. His argument rested on the concept of 'reproductive liberty'.

"The corner of the notion of reproductive liberty is that the decisions about reproduction should be left to the people that are reproducing," he said.

In relation to stem cells, Sparrow said it could be argued that the people reproducing are the genetic parents of the embryo. In relation to therapeutic cloning, Sparrow said, "my clone is my identical twin and the genetic offspring of my parents. It is their child -- so if we accept the reproductive liberty is important, and we accept this genetic relationship is important, it would be a violation of my parents' reproductive liberty to destroy my embryo.

"I think there is some case to be made that my parents should have a veto ballot over that procedure," he said.

While Sparrow said there are various ways to avoid this argument, "if we are to realise the promise of stem cell therapies, we need to work out how we are going to do that."