Originally created 07/23/98

Mice cloned with improved technology



In what could be a big boost for all sorts of biomedical research, scientists in Hawaii have turned out more than 50 carbon-copy mice using what is believed to be a more reliable cloning technique than the one used to create Dolly the sheep.

The scientific potential could be broad because mice are the best-understood and most commonly used animals in biomedical experiments. Having genetically identical copies of the same animal could speed research in fundamental biology and virtually every branch of medicine and drug development.

The University of Hawaii scientists, reporting in Thursday's issue of the journal Nature, describe their work as "the first reproducible cloning of a mammal from adult cells" extending at least three generations.

They said it is a marked improvement over the method used to make Dolly, which other laboratories so far have failed to duplicate.

Biologists in the United States and Europe hailed the mice-cloning effort as having much greater potential than the cloning of more complex creatures such as Dolly or a pair of calves that were born earlier this month in Japan.

"The importance of this report cannot be overemphasized," said Davor Solter, a biologist at the Max Plank Institute in Germany.

Researchers said that with the Hawaii cloning method, cattle and pigs could be reprogrammed with human genes to mass-produce proteins essential to treat illnesses such as diabetes and Parkinson's disease. Animals could custom-grow organs for transplantation.

And because mice give birth three times a year, experiments employing identical rodents could progress more rapidly than those relying on slower-reproducing barnyard animals.

"Genetics will become much more accessible to us," said Virginia Papaioannou of Columbia University.

The Hawaii scientists would not discuss whether their technique might make human cloning more feasible.

Researchers introduced four of the cloned mice -- all females -- Wednesday in New York. The original clone was named Cumulina after the type of cell used in its creation; she remained in Hawaii.

Working in a windowless lab for 16 hours a day, the Hawaii group used an injection method dubbed the "Honolulu technique" to transfer genetic material from adult mice to an empty egg. In each of four experiments beginning in 1997, the team transferred up to 800 eggs containing adult genes into surrogate mice mothers.

Three survivors from the original group, including Cumulina, grew to adulthood. Those clones eventually yielded cells that by this week had generated more than 50 offspring.

DNA testing by an independent laboratory confirmed that none of the rodents are carrying stray DNA from other mice.

"We succeeded in using both a new method and a new type of cell to clone mice from adult cells, and in repeating it to produce clones of clones of clones," said Teruhiko Wakayama, lead author of the Hawaii study.

The Hawaii group's emphasis on repeating the clones is an indirect rebuke of geneticist Ian Wilmut and his colleagues in Scotland who created Dolly in one out of 277 attempts in the lab.

Repeating an experiment to verify a discovery is central to scientific research. But at least three other laboratories have failed to duplicate the sheep experiment using Wilmut's method over the past 18 months, prompting scientists to question whether Dolly is truly a clone.

In Thursday's issue of Nature, Wilmut and 17 other researchers in Britain reported that an exhaustive examination of Dolly's genes show that it is "extraordinarily unlikely" that the sheep is anything but a clone.

Dolly was created by a technique known as electrofusion, in which the membrane of an egg was breached, the chromosomes were removed and the nucleus of an adult sheep cell with different genetic material was merged inside.

In the Honolulu technique, the nucleus of a cell from one mouse was injected through a tiny needle into an egg donated by a second mouse. The egg's original genetic package was removed. The donor nucleus came from cumulus cells, which surround the developing eggs in the ovaries of female mice.

Up to 3 percent of the manipulated eggs developed into surviving clones, a much higher success rate than the electrofusion method had.