
It seems that every week, newspapers report on new advances in the science of cloning. Everybody knows about Dolly the cloned sheep, but few people know all the details about cloning, including the fact that scientists have been working on it for over 100 years.
Cloning in Nature
Cloning has been going on
in the natural world for thousands of years. A clone is simply one
living thing made from another, leading to two organisms with the same
set of genes. In that sense, identical twins are clones, because
they have identical DNA. Sometimes, plants are self-pollinated, producing
seeds and eventually more plants with the same genetic code. Some
forests are made entirely of trees originating from one single plant; the
original tree spread its roots, which later sprouted new trees. When
earthworms are cut in half, they regenerate the missing parts of their
bodies, leading to two worms with the same set of genes. However,
the ability to intentionally create a clone in the animal kingdom by working
on the cellular level is a very recent development.
Early Progress
The first cloned animals
were created by Hans Dreisch in the late 1800's.
Dreich's original goal was not to create identical animals, but to prove
that genetic material is not lost during cell division. Dreich's
experiments involved sea urchins, which he picked because they have large
embryo
cells, and grow independently of their mothers. Dreich took a 2 celled
embryo of a sea urchin and shook it in a beaker full of sea water until
the two cells separated. Each grew independently, and formed a separate,
whole sea urchin.
In
1902, another scientist, embryologist Hans Spemman, used a hair from his
infant son as a knife to separate a 2-celled embryo of a salamander, which
also grow externally. He later separated a single cell from a 16-celled
embryo. In these experiments, both the large and the small embryos
developed into identical adult salamanders. Spemman went on to propose
what he called a "fantastical experiment" -- to remove the genetic material
from an adult cell, and use it to grow another adult. In this way,
he theorized, he would be able to prove that no genetic material was lost
as cells grew and divided.
New Advances
There
were no major advances in cloning until November of 1951, when a team of
scientists in Philadelphia working
at the lab of Robert Briggs cloned a frog embryo. This team did not
simply break off a cell from an embryo, however. They took the nucleus
out of a frog embryo cell and used it to replace the nucleus of an unfertilized
frog egg
cell, completing the "fantastical experiment"
of nearly 50 years before. Once the egg cell detected that it had
a full set of chromosomes, it began to divide and grow. This was
the first time that this process, called nuclear transplant,
was ever used, and it continues to be used today, although the method has
changed slightly.
False Hopes
In
1977, a German scientist shocked the world, claiming to have cloned three
mice from embryos. Although embryos had been cloned before, no one
had been able to do the experiment with mice because the cells were so
small and the tools so large that the cells were traumatized and would
eventually die after a few divisions. He instantly became famous,
telling the world how he cloned his mice. However, he refused to
actually demonstrate any of his techniques, and when other scientists couldn't
replicate his work, he came under suspicion. He was challenged --
repeat his work or be discredited. He accepted.
He
claimed to work nights and mornings when no one was around, but the equipment
was never disturbed. He showed off his mouse embryos' growth daily,
even though a malfunction in the water purification system left other scientists
at his lab unable to grow other embryos. Later, in his cabinet, test
tubes were found with mouse embryos in them, each at a different stage
of development. Most scientists do not believe that this scientist
was ever able to clone adult mice.
In
1978, a science fiction writer published a book claiming that a millionaire
(known to the readers only as Max) had come to him because of his connections
as a writer, and asked the him to arrange for Max to be cloned. The
author eventually agreed, as the story goes, and Max was cloned.
The book was ranked in the Top 10 list of popular books. Scientists
who read his book, however, noticed discrepancies between the book and
scientific data. One man who was quoted in the book was angry enough
to sue. The publisher admitted that the book was a hoax, but the
author maintains his claim to this day.
Within
these two years, two front-page advances in cloning were discovered to
be, most likely, frauds. As a direct result, many scientists began
to claim that cloning of mammals was impossible. Funding and interest
dropped, and cloning returned to the realm of science fiction for several
years.
First Cloned Mammals
A
breakthrough came in 1986. Two teams, working independently but using
nearly the same method, each on opposites side of the Atlantic, announced
that they had cloned a mammal. One team was led by Steen Willadsen
in England, which cloned a sheep's embryo. The other team was led
by Neal First in America, which cloned a cow's embryo. Many
advances were made during the course of these experiments, including progress
in keeping tissue alive in lab conditions. However, neither team
believed that it was possible to clone from an adult's differentiated
cells. With no progress in sight, the prospect
of cloning fell by the wayside, and little research was done on the matter.
Dolly
Ian
Wilmut at the Roslin Institute in Scotland was assigned to a project in
1986. His goal was to create a sheep that produced a certain chemical
in its milk. He chose to alter adult cells, which held up well in
laboratory conditions, and then clone them, producing animals with the
altered gene all throughout their bodies. He began the paperwork
in 1987, and began research in 1990.
One
of Wilmut's colleagues, who had experience with cloning from early embryo
cells, suggested that the reason so many cloning attempts failed
was that the cells were in incompatible stages of life. In one stage,
the cells are adding to the DNA, in another, they are proofreading it,
and in another, splitting it. The cells, he theorized, could not
always start over. Wilmut's team learned that by starving the cells,
they could be forced into what is called the G0 phase, similar to cellular
hibernation. This advance increased the survival rate of the cloned
cells; Megan and Morag, two lambs, were cloned from sheep embryos.
Wilmut's team now realized
that differentiation did not matter in cloning. More work was done,
and on July 5, 1996, a lamb was born, cloned from a frozen mammary cell
from another adult sheep. Wilmut, who names his animals very creatively,
named her Dolly after Dolly Parton.
Although Dolly was just
a step in a long experiment, the press descended upon the first animal
cloned from an adult. The Roslin Institute was overrun with journalists
and reporters. However, other scientists were critical -- Dolly took
277 tries to create, and other labs were unable to reproduce the results.
In addition, it took over a year for the institute to test Dolly's DNA
to make sure that it was indeed the same as that of the frozen mammary
cells. Science, although temporarily impressed, demanded a better
way.
Herd of Mice
Oct
3, 1997, the Honolulu Technique created Cumulina the cloned mouse.
She was cloned from cumulus cells (cells which surround developing egg
cells) using traditional nuclear transfer. The nucleus was taken
from the cumulus cell and implanted in an egg cell from another mouse.
The new cell was then treated with a chemical to make it grow and divide.
The scientists repeated the process for three generations, yielding over
fifty mice that are virtually identical by the end of July, 1998.
The Honolulu Technique's success rate of 50:1 is almost six times better
than that of the Roslin Institute's success rate, 277:1. As cloning
technology improves, more and more applications will be seen in everyday
life.
Mainstream Cloning
How
much do you love your dog? Is your dog so perfect that you would
pay over $2.3 million dollars to have another just like it? One couple
thinks their 11-year-old dog is just such an animal. Wishing to remain
anonymous to avoid run-ins with the press, this couple has contracted Texas
A&M University to clone their dog, Missy. Scientists are hailing
this for its scientific achievement; no dogs have been cloned before because
their reproductive system is rather complicated. If the cloning of
dogs can be achieved, perhaps exceptional animals like rescue animals can
be reproduced.
In
addition to the pure scientific appeal of cloning a dog, the attempt to
clone Missy has another interesting addition to make to the history of
cloning. A private couple wants their dog cloned. They are,
of course, spending millions to have her cloned, but consider the possibilities.
Could cloning the family pet one day become a normal alternative to buying
a new one?
Applications
Reliable
cloning can be used to make farming more productive by replicating the
best animals. It can make medical testing more accurate by providing
test subjects that all react the same way to the same drug. It can
allow mass production of genetically altered animals, plants, and bacteria.
It may settle once and for all what part of personality is dependent on
genetics and what part on environment. In short, it can be beneficial
to almost every area of biological science.