From - Thu Mar 13 12:19:11 1997
From: Archimedes.Plutonium@dartmouth.edu (Archimedes Plutonium)
Newsgroups: sci.bio.misc,sci.med,sci.bio.technology,sci.physics.electromag,sci.physics
Subject: Re: 1997 Nobel prize in Physiology and Medicine to Dr. Wilmut and team
Date: 7 Mar 1997 19:55:19 GMT
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--- quoting from 3Mar97 NYT ppA20-A22 ---
1938  
Cloning is envisioned
Hans Spemann proposed what he called a "fantastical experiment." He
suggested taking the nucleus from a cell of a late-stage embryo,
juvenile or adult and transplanting it into an egg. In other words,
cloning.

1952
 First cloning experiment with frogs
Robert Briggs and T.J.King used a pipette to suck the nucleus from the
cell of an advanced frog embryo and added it to a frog egg. It did not
develop.

1970
Another experiment on frogs yields better results
John Gurdon tried the same procedure. The eggs developed into tadpoles
but died after they were ready to begin feeding. He later showed that
transplanted nuclei reverted to an embryonic state.

Even though the frogs never reached adulthood, the technique used was a
milestone.  He replaced the nucleus of a frog egg, one large cell, with
that of another cell from another frog.
Although scientists could transfer nuclei from adult cells to egg
cells, the frogs only developed to tadpoles, and they always died.

Nucleus taken from a multicell frog embryo.
Nucleus implanted into egg. Cell division. Tadpole.  Frog.

1981
Cloning of mice is claimed
Karl Illmensee and Peter Hoppe reported that they produced normal mice
from mouse embryo cells.
After a lengthy inquiry, it was discovered that Dr. Illmensee had faked
his results.


1982
Research stalls
James McGrath and Davor Solter reported that they could not repeat the
mouse-cloning experiment and conclude that once mouse embryos have
reached the two-cell stage they cannot be used for cloning. Others
confirm their results.

1984
First embryo cloning with sheep is reported
Steen Willadsen reported that he cloned a live lamb from immature sheep
embryo cells. Others later replicate his experiment using a variety of
animals, including cattle, pigs, goats, rabbits and rhesus monkeys.

Nucleus taken from a multicell sheep embryo.  Nucleus implanted into
egg.  Cell division.  Fetus.  Lamb.

1994
First cloning of more advanced embryo cells.
Neal First cloned calves from embryos that have grown to at least 120
cells.

Nucleus taken from a multicell cow embryo.  Nucleus implanted into egg.
 Cell division.  Fetus.  Calf.

1996
Groundwork laid for cloning of adult sheep
Ian Wilmut repeated Dr. First's experiment with sheep, but put embryo
cells into a resting state before transferring their nuclei to sheep
eggs. The eggs developed into normal embryos and then into lambs.

Because no one knew whether cloning was even possible, it was hard to
speculate about what the hurdles might be. But Dr. Campbell had what
turned out to be the crucial insight. It could be, he realized, that an
egg will not take up and use the genetic material from an adult cell
because the cell cycles of the egg and the adult cell might be out of
synchrony. All cells go through cycles in which they grow and divide,
making a whole new set of chromosomes each time. In cloning, Dr.
Campbell speculated, the problem might be that the egg was in one stage
of its cycle while the adult cell was in another.
   Dr. Campbell decided that rather than try to catch a cell at just
the right moment, perhaps he could just slow down cellular activity,
nearly stopping it. Then the cell might rest in just the state he
wanted so it could join with the egg.
...
  What he decided to do was to force the donor cells into a sort of
hibernating state, by starving them of some nutrients.

... In Wisconsin, Dr. First had actually beaten the Scottish group to
cloning a mammal from cells from an early embryo; that occurred when a
staff member in the laboratory forgot to provide the nourishing serum,
inadvertently starving the cells. The result, in 1994, was four calves.



1997
Adult sheep are cloned
Dr. Wilmut reported that he had cloned a 6-year-old adult sheep from an
udder cell.

Nucleus from an adult sheep.  Nucleus implanted into egg.  Cell
division.  Fetus.  Lamb.

"You greatly reduce serum concentration for five days," Dr. Wilmut
said. "That's what we submitted a patent for." And that is why the team
was silent about the lamb's birth for months. Until the patent was
applied for, nobody wanted the news to spread.

... Dolly was the only lamb to survive from 277 eggs that had been
fused with adult cells.
   The cell fusion that produced Dolly was done in the last week of
January 1996.


PPL Therapeutics P.L.C. ... run by Ron James, a
biochemist-turned-entrepreneur.

  Dr. Neal First and Dr. Miassam M. Matalipova in their laboratory at
the University of Wisconsin.... using a pipette to remove genetic
material from a cow egg, as shown above. A skin cell from a calf fetus
was then inserted under the egg's outer coating and fused with it,
using an electric shock.

... For eggs, researchers have discovered, a jolt of electricity does
the trick. If they give an egg an electric shock, it will briefly open
its pores and undergo the same biochemical reactions -- the surge of
calcium, the burst of enzyme activity -- that starts the cell on the
path to dividing after a sperm penetrates an egg.
   So Dr. Matalipova put two electrodes onto the glass slide and ran a
tiny current through them. She gave the egg a brief jolt of current,
lasting thousandths of a second.
  Under the microscope, it looked as though nothing had happened. The
fetal cell was still in place under the outer skin of the egg. But over
the next four hours, its contents would ooze into the egg.

Many in the reproductive-medicine community believe that he could probably achieve this goal if he set out to do so, citing his track record in assembling top-flight teams of researchers and technologists.

Dr. Seed's goal in this case is to allow childless couples to raise children. He says he has volunteers who wish to raise a child who would be the clone of one of the parents.

There is, however, a huge and ongoing ethical debate concerning the ramifications of cloning human beings. The National Bioethics Advisory Commission has recommended that the cloning of human beings be made illegal in the United States. Dr. Seed has stated that if cloning is banned in the US, he will simply move his operation abroad.

19 January 1998 - The US Food and Drug Administration (FDA) announced that it is the Federal body which has power to regulate the cloning of human beings within the United States. It's rationale and claim to venue is that human somatic cell nuclear transfer (cloning) is a form of cellular or genetic therapy, which is already regulated by the FDA.

Interestingly, in the face of increasing threats by various legislators to introduce legislation which would result in an outright ban on the cloning of human beings, this assertion of authority by the FDA may provide a recourse to scientists pursuing lines of research which may required cloning of human beings. Research on cloned embryos, for example might well lead to breakthroughs in the fields of genetics, or cancer research, or longevity.

22 July 1998 - Scientists working at the University of Hawaii cloned five generations of mice from adult mice. Clones of clones were produced with reproducible technology, all appear to be healthy. The particular technology has been licensed to ProBio America, Inc.

14 February 2003 - "Dolly the Sheep" was euthanized after a prolonged lung illness.

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