Japanese Scientist Makes Frog Eyes

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Story Filed: Sunday, March 24, 2002 12:05 PM EST

TOKYO (AP) -- Professor Makoto Asashima is surrounded in his tiny laboratory by shelves cluttered with bottles of chemicals. Test tubes whirl in centrifuges while technicians pore over data at their desks.

The scene is a typical one, but what goes on here isn't. Immersed in water at the bottom of a petri dish are about a dozen frog embryos the size of a pinhead that Asashima uses to create the animal's eyes, ears and other organs.

Technology that Asashima is developing could eventually help doctors use stem cells from humans to regenerate or replace damaged or destroyed human organs, like the way a lizard reproduces a severed tail. It would eliminate the need for donor transplants.

``If we keep going in this direction, it'll be possible for people who have lost their sight to see again,'' said Asashima, professor of developmental biology at Tokyo University.

About two decades after starting research on organ regeneration, Asashima in 1989 discovered that a protein called activin induces genes in a frog's embryonic stem cells -- which produce the tissues and organs of the body -- to form kidneys, livers and other organs.

In 1998, he became one of the first scientists to create a sensory organ -- a frog eye -- in vitro from a stem cell. Last year, he successfully transplanted an eye formed in a test tube, restoring the sight of a blinded tadpole.

So far, Asashima and his team have given new eyes to some 60 tadpoles, about 70 percent of which are able to see.

``It's a good example of his type of pioneering work. He's really on the forefront,'' said Carl Pfeiffer, emeritus professor of biomedical sciences at Virginia Polytechnic and State University.

Asashima generates organs by slicing off the part of the embryo responsible for tissue development and immersing it in a solution containing activin. The activin-soaked embryo piece is sandwiched between two untreated embryo slices and set aside until the untreated parts are induced to yield an organ.

The process takes about five days. Varying the concentration of activin and combining it with other agents such as retinoic acid brings forth different genetic instructions in the cells.

For example, a lower concentration produces blood cells and muscle tissue. Higher doses yield hearts, livers and pancreas. But Asashima concedes it's a big step from regenerating frog organs to doing the same for humans.

For one thing, frogs produce many more embryos than humans, meaning the number of stem cells available for research on humans would be more limited.

Then there are also political concerns about research with human stem cells.

Anti-abortion activists and the Vatican say that human stem cell research constitutes the taking of life because embryos are destroyed to extract the cells. And President Bush decided last year to withhold federal money for research that involves the destruction of embryos not already in the research pipeline.

In Europe, four countries -- Austria, Germany, France and Ireland -- ban all embryo research, while others allow it to varying degrees.

Japan falls somewhere in between, approving guidelines last year stipulating that embryonic cells used in experiments could be taken only from those earmarked for fertility treatment that would otherwise be discarded.

Politics aside, some experts anticipate that Asashima's research will eventually help scientists to cure debilitating diseases such as Alzheimer's, which is caused by the degeneration of brain cells.

``The principles he develops in lower animals will be applicable to humans,'' Pfeiffer said.

Despite the obvious differences, Pfeiffer said humans and frogs have much in common, including similar heart and skeletal muscles.

Others, however, are somewhat less sanguine.

``They (human stem cells) will form various tissues, but not intact organs, and even if they could be formed, the organs would have to be grown for months to become big enough for transplantation,'' said professor Jonathan Slack, who is in charge of the department of biology and biochemistry at the University of Bath in the United Kingdom.

``This is interesting science but it would be a very long haul before it leads to a new source of transplantable organs,'' he said.

Asashima's work is funded by Tokyo University and a government-linked science promotion group. His research has appeared in major international publications in his field, including The International Journal of Developmental Biology.

Asashima plans to expand his research to mice, whose characteristics are more similar to humans, as soon as he perfects his work with frogs.

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