Two new cloning studies have scientists scratching their heads
11 February 2002
The world's labs are home to a steadily growing number of cloned animals. "From a practical viewpoint, cloning is more or less solved," says Davor Solter of the Max Planck institute for Immunobiology, Freiburg, Germany. "But the really important questions are so hard we don't know how to approach them."
One of the biggest of those questions is what happens when researchers try to reprogram adult cells to develop into new embryos. Two studies now provide vital clues. But an answer is still a long way off.
Japanese researchers have found that cloned mice sicken and die earlier than their normal counterparts (1). A US team has gone a long way towards proving that adult cells that are fully committed to doing a particular job can become new embryos (2).
Atsuo Ogura, of the National Institute of Infectious Diseases in Tokyo, and his colleagues compared 12 cloned mice with 7 normal mice and 6 that were created by injecting sperm DNA into an egg, to replicate the manipulation used in cloning.
Of the 12 cloned mice, 10 died of pneumonia and liver disease before they were 800 days old (the normal mouse lifespan). One normal mouse and two that were produced by sperm injection died during this time.
Most clones die either before birth or soon after. Ogura's results suggest that the odds are still stacked against animals' throughout their lifespan. "It is very probable that, at least for some clones, unpredictable defects will appear in the long run," says Ogura.
The cloning process probably always fails to achieve the accuracy of natural reproduction, says Solter. "Whether the clones dies next day or next year depends on how badly it misses," he suggests.
But Tony Perry, of biotechnology company Advanced Cell Technology, based in Worcester, Massachusetts, believes that the study "gives us great cause for hope". He feels that the results hint that clones' problems might be caused by the techniques used to create them, rather than by fundamental biological inadequacies.
Technical refinements, says Perry, might give rise to healthier clones. "What's needed is standardization," to move the technology from being an art to a science, he says.
Secret of cells' success
Biologists have long tried to work out what makes some cells yield successful clones.
One possibility is that the animals that make the grade were cloned from one of the rare stem cells found in adult bodies. These have more potential to develop into different tissue types than the majority of cells, which are fully committed to a particular job.
To rule out this possibility, one needs to create clones from a cell that carries a badge of rank. Cells in the immune system called lymphocytes have genetic rearrangements that distinguish them from the body's other cells - making them ideal for this purpose.
Konrad Hochedlinger and Rudolf Jaenisch, of the Whitehead Institute in Cambridge, Massachusetts, took DNA from a lymphocyte and put it into an egg. They did not let this egg develop into a mouse, but instead extracted embryonic stem cells from the early-stage embryo, and then created clones from these. Embryonic stem cells have a higher cloning success rate than cells from adult bodies.
One thousand attempts yielded two stem-cell cultures, which gave rise to 21 live-born mice from 260 attempts.
"We've proved that you can reprogramme mature cells, but that it's very, very inefficient," says Jaenisch. Jaenisch and Hochedlinger's two stem cell lines from 1,000 attempts compares unfavourably with Dolly the sheep, for example, who was the single success from 277 attempts. Jaenisch argues that this strengthens the idea that previous clones were indeed made from cells that weren't fully set on a particular course.
Solter is not so sure. "I don't think this proves you can clone from a differentiated cell, and, on the other hand, I don't think it proves that all successful clones were from adult stem cells," he contends.
"It's a step forward, but it's really
a warm-up act for the main event, which would be cloning directly from
a lymphocyte," says Perry.