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Cloning without embryos

IT’S the acceptable face of human cloning: creating new cells and tissues to
replace those lost to disease. But even the prospect of this “therapeutic
cloning” has a troubling side. Every time a patient is treated, a cloned human
embryo would be destroyed—a tiny ball of cells admittedly, but a potential
human life nonetheless.

Now a company linked to the team that created Dolly the sheep plans to
overcome this ethical obstacle by removing the embryo step. It claims already to
have promising results. And the technique wouldn’t need to use human egg cells,
which are scarce and in demand for IVF patients.

Therapeutic cloning could revolutionise the treatment of conditions such as
Parkinson’s disease. Doctors would take a healthy cell from the patient and fuse
it with a human egg stripped of its own chromosomes to create a cloned embryo. A
few days later, when the embryo has grown in a culture dish into a ball of cells
called a blastocyst, they would remove the embryonic stem cells, which can
develop into any of the body’s tissues. Once biologists have discovered the
triggers that will persuade stem cells to turn into the brain cells a
Parkinson’s patient needs, it should be possible to grow cells that are a
perfect match for each patient.

But Geron BioMed, a company launched by the team that cloned Dolly at the
Roslin Institute near Edinburgh, is now working on cloning techniques that
dispense with human eggs. In conventional cloning, the gutted egg reprograms the
genes of the donor cell, winding back their developmental clock. But Simon Best,
Geron BioMed’s managing director, thinks it will be possible to achieve this
trick using embryonic stem cells, rather than eggs.

In this case, the reprogrammed cells wouldn’t form an embryo, but instead
develop directly into the cells or tissues the patient needs. Ardent pro-life
groups may still object to scientists using embryonic stem cells because they
are derived from a human embryo. But it would greatly reduce the number of
embryos sacrificed, because limitless supplies of embryonic stem cells can be
grown in culture.

Significantly, British patents on cloning awarded to the Roslin team last
week are worded to include the new technique. Rather than specifying eggs, the
patents describe the fusion of a donor cell with “a suitable recipient
”.

The research that inspired Geron BioMed’s new approach was published with
little fanfare around the time that Dolly arrived on the scene. In 1997,
researchers led by Azim Surani of the Wellcome/ CRC Institute of Cancer Research
and Developmental Biology in Cambridge revealed in The EMBO Journal
(vol 16, p 6510) that they had merged mouse thymocytes, a type of white blood
cell, with mouse embryonic germ cells—stem cells that ultimately develop
into sperm or eggs. After each merger, the white blood cell’s genetic slate was
unexpectedly wiped clean. What’s more, the resulting hybrid cells could develop
into a wide variety of different tissues, just like embryonic stem cells.

Surani has agreed to collaborate with Geron BioMed, but warns of difficulties
using the Dolly technique on stem cells instead of eggs. To obtain cells and
tissues that match a patient, you would need to fuse one of the patient’s cells
with a gutted embryonic stem cell. Surani fears that, unlike eggs, gutted stem
cells won’t make all the substances needed for reprogramming.

But Best remains optimistic. “We’re trying it with mouse cells and sheep
cells. We have some completely novel ideas which we can’t disclose now. Once we
confirm the hypothesis in sheep, we might be able to try it in people three
years later.”

If so, Geron BioMed would be in pole position to exploit therapeutic cloning.
Its parent company, Geron of Menlo Park, California, has an exclusive licence to
commercialise human embryonic stem cell technology.

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