Recall that previous animal clones were made by dividing an existing embryo -- the result of normal fertilization -- into several daughter cells. (Plant cells are routinely cloned in a process called tissue culture, which grows adult plants from cells taken from rapidly growing parts of the plant.) Instead, Ian Wilmut fused two cells. One contained the DNA he wanted in the adult. The other contained the cellular machinery to support the new DNA.
Although it sounds otherworldly, the technique was fairly simple biotechnology. Let's use the familiar photocopier as a metaphor for the process, and imagine a sheep named Belinda as the original page we want to copy.
|1.||Wilmut's team isolated a mammary cell from Belinda's udder and put its genes to "sleep." Most living cells pass through a "cell cycle" in which their chromosomes (defined) are either preparing to divide, dividing, or recovering from division. Brigid Hogan, a Vanderbilt University cell biologist, observes that when DNA is reproducing before the cell divides, some of it is in fragments, with part of its protein coat disassembled. Moving such a bundle of trouble would be about as easy as moving a chicken egg without the shell. But Wilmut solved his transportation problems by putting the chromosomes in a "quiescent," or dormant, state. Rather than using sleeping pills, Wilmut withdrew the serum containing the growth factors (defined) that normally stimulate genes to reproduce. Jump ahead to our nuts-and-bolts on DNA mechanics.|
|2.||The researchers grabbed some unfertilized egg cells from Fluffy and sucked out their nuclei (defined), which contain the genetic material. Think of Fluffy's egg cell as the copier cartridge -- the core of the technology that makes the copies.|
They put Belinda's mammary cell in a dish with Fluffy's egg cell, and added a protein that caused the cells to fuse. After the cell walls joined, all that was left was an egg containing Belinda's DNA.
Why bother moving the chromosomes into the host cell? Because the protein coat on chromosomes in an adult cell directs the chromosomes to make only proteins that cell needs -- even though the cell has the genes to make any protein in the body. (Thus mammary cells make only milk, not muscle, nerve or bone.) But once the nucleus is moved to the egg cell, the "adult" protein coat is replaced by an "egg" protein coat, which directs the chromosomes to act like the chromosomes of an egg cell, and develop as a normal embryo.
The researchers gave the cell a tiny jolt of electricity to jump-start the cell cycle they'd previously stalled.
Then the researchers implanted the egg into another sheep -- call her Lassie -- which brought it to term. Think of Lassie as the copy machine -- the source of the power and chemical environment for the copying operation.
The cell then developed normally into Dolly, Nature's cover girl, and passed genetic tests to make sure she was who the researchers thought she was -- the offspring of a mammary cell in a ewe (adult female sheep) unmixed with any other DNA.
Dolly was born last July. But some elements of the cloning technology were anticipated years ago. Let's look at a simple time line
1938: Long before the structure of DNA is known, Hans Spemann suggested taking a nucleus from one cell and transferring it into another cell. Spemann, a pioneering embryologist from Germany, never gives it a try.
1953:James Watson and Francis Crick correctly deduce that DNA is made of two strands of material arranged in helical fashion. Their famous "double helix" proposal sets the stage for the biotechnology revolution.
1970: Scientists learned to clone frog embryos, but they (the tadpoles, not the scientists) did not mature properly.
1981: Two scientists fraudulently claimed they'd cloned mice. The inability to replicate (defined) their bogus work drenched the gathering fire of scientific and entrepreneurial interest in cloning.
1984: A live lamb was produced from a division of an early-stage embryo.
1994: Neal First, of the University of Wisconsin-Madison, was the first (no typos here!) to clone a mammal (a cow) from an advanced embyro.
All these steps had been pushing the envelope -- testing whether the process of development forced the genes through a one-way street. Could genetic material go "backward," from a more-differentiated cell to a less-differentiated one?
No one knew, and publicly, scientists discounted the possibility -- until Dolly's wooly face graced the cover of Nature, Britain's most prestigious science journal and her story became global headlines. Instantly, speculation ran rampant about the possibility of cloning a common, two-footed mammal.
Before we get to that juicy stuff, what scientific questions could Dolly help answer?
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