The great cell breakout

Scientists' latest extraordinary cloning research is bringing hope to victims of strokes, cancer, Alzheimer's and infertility

ONE DAY in September last year, Alma Cerasini experienced a sensation that would change her life. A tiny blood vessel ruptured in her head and quickly starved some of her brain cells of vital oxygen. The stroke left her paralysed in the right leg and almost speechless. She was 62 and lucky to survive.

Mrs Cerasini, a nurse, was also lucky to live near the University of Pittsburgh, where American scientists were searching for volunteers for a radical form of stroke therapy. And in June this year she made history by becoming the first person to receive injections of laboratory-grown nerve cells.

Surgeons at the Pittsburgh Medical Centre, led by Douglas Kondziolka, drilled a hole into their patient's skull and injected about 2 million cells which they had grown from a batch of cells extracted 25 years previously from a man suffering from a rare type of cancer.

These cells exhibited an unusual trait. Under certain conditions in the laboratory they could be stimulated to grow into fully mature nerve cells and, once they had finished developing, they stopped becoming cancerous. The hope is that they will do the same in the brains of Mrs Cerasini and the 10 other stroke victims taking part in the first clinical trial of a brain-cell transplant of laboratory-cultured nerves.

There are obvious risks attached to the transplant experiment. One is whether the doctors can be sure that the cells really will stop being cancerous. Another is whether the patient's immune defences will accept the foreign tissue - rejection is the continuing nightmare of any transplant surgeon. A third is whether the injection will do any good anyway. Who is to say whether the apparently normal-looking nerve cells from a man's bizarre cancer can carry out the functions of Mrs Cerasini's lost brain cells?

A better alternative, however, will soon be possible. Scientists at the University of Wisconsin-Madison demonstrated last week that they have found the mother of all cells in the body. This is the "embryonic stem cell" that appears early in the development of an embryo, within about a week after fertilisation, and which matures into any one of the many different types of tissues, such as bone, blood, muscle, skin or nerves.

To give Mrs Cerasini the best of all possible chances of recovery, it would be better to use her own embryonic stem cells, but at 62 years old this is 62 years too late. Or is it? What if scientists could clone one of her skin cells, say, and let it develop into a week-old embryo which could then be used to extract the vital stem cells?

This scenario is not as fantastic as it might seem. The scientists at the Roslin Institute in Edinburgh, who cloned Dolly the sheep, and some of the leading researchers in human embryonic stem cells, are now finalising plans to begin work on achieving the marriage of two biological disciplines. This, they believe, will lead to a revolution in the treatment of what are now incurable diseases, such as strokes, Alzheimer's, cancer, heart disease or even infertility.

HUMAN embryology raises huge ethical concerns in its own right (chiefly among anti-abortionists), but when it also involves cloning, the anxiety is even greater. The fears have been well exercised in works of fiction, from Aldous Huxley's vision of a cloned race of sub-intelligent workers to the nightmare scenario of the 1970s film Boys from Brazil, where clones of Hitler are raised secretly in the South American jungle.

Austin Smith, director of the Centre for Genome Research at Edinburgh University, said people should not worry that his and the University of Wisconsin's collaboration with the Roslin might produce adult human clones.

In his submission to the consultation on cloning by the Human Fertilisation and Embryology Authority (HFEA), Dr Smith said it was crucial to distinguish between "reproductive cloning", used to produce a child, and "therapeutic cloning"- which is potentially of enormous clinical benefit - where cells are derived from an early cloned embryo for medical use. Harry Griffin, assistant director of science at the Roslin Institute, is equally adamant that the use of Dolly technology to produce a human embryonic clone will not increase the chances of someone actually cloning children. "Embryonic stem cells are not the cellular equivalent of an embryo," he said.

"They are derived from what is called the inner cell mass of an early embryo. Other cells are needed for implantation and embryogenesis."

Nevertheless, in order to extract embryonic stem cells an embryo has to be created by effectively cloning a human being. In the case of Mrs Cerasini it would involve extracting the nucleus from one of her skin cells and injecting it into an unfertilised human egg cell which has had its own nucleus removed.

If this could be made to divide in the same way that Dolly's original cell divided, then the resulting embryo would effectively be a clone of Mrs Cerasini and have the potential to develop into a full-grown adult. What the Roslin and Dr Smith are proposing is that the embryo should never be allowed to develop beyond 14 days, the current legal time limit allowed for human embryos to develop after in vitro fertilisation.

Dr Griffin proposed additional safeguards. "Reconstructed embryos would need to be cultured for probably no more than seven days," he said. "Moreover, in the future, when we know more about the mechanism involved in nuclear transfer, it may be possible to avoid creating a potential embryo by 'reprogramming' the specialised cells in the test tube rather than in the egg."

ONE future scenario painted by Dr Smith is the prospect of all new-born babies routinely having clones developed of themselves in order to extract their embryonic stem cells for freezing in a tissue bank. A precedent exists already in the national tissue bank for embryonic blood cells derived from the umbilical cord of newborns, which can be used to extract important blood-forming cells for the treatment of leukaemia and similar illnesses.

"The significance of producing embryonic stem cells is that they can be amplified indefinitely in culture, can be subjected to precise genetic modification, and can be induced to differentiate into a broad range of cell types," Dr Smith says in his submission to the HFEA. "In order to incorporate nuclear cloning, however, the scope of currently permitted human embryo research would have to be broadened to encompass therapeutic applications. Such an extension to the legitimate subjects of research is justified, indeed demanded, by the prospective benefits of developing patient-specific stem cells."

The HFEA has made it clear that, as things stand, it would refuse to issue a licence to anyone proposing to clone human cells using the nuclear transfer method of the Roslin Institute. It accepts, however, that there may be sound medical reasons why it might be allowed in the future. It now appears that at least two groups of scientists are about to test the regulatory water on human cloning for the benefit of the thousands of people like Mrs Cerasini.