In Scotland's Roslin Institute, where Dr. Ian Wilmut had been trying for years to create sheep that would make milk containing valuable proteins, a lamb named Dolly was born last July. Dolly didn't look weird, but she was the first mammal in history that was a carbon copy of an adult mammal (a sheep we'll call Belinda). Wilmut started making Dolly by extracting some mammary gland tissue from Belinda and putting the DNA in one of the cells to "sleep." Then he snarfed (defined) an unfertilized egg cell from another sheep (call her Fluffy) and sucked out the nucleus with a practically invisible pipette (defined). The nucleus contained Fluffy's chromosomes. Without the genetic file called "Fluffy," the egg cell was a husk of a cell, with neither identity nor ability to reproduce.
At that point, Wilmut had two cells with one set of genes. So he did the obvious thing: He fused the two cells, then gave the single cell he'd created a jolt of electricity. That woke up the sleeping cell machinery and caused the genes to reactivate. Finally, he implanted the egg into yet another sheep (call her Lassie) where the egg grew up into a copy of Belinda, identical down to virtually the last genetic detail.
Six months after Dolly's birth, Wilmut went public with his discovery. He waited to make sure that the lamb would actually develop into an adult -- in previous experiments, cloned frogs developed a bit, then croaked in the tadpole stage.
What's the big deal?
As we've said, scientists have been cloning (defined) mammals for almost a decade. But these genetically identical animals were made with a technique like the one that nature uses to make identical twins -- dividing an embryo into identical pieces, which then develop into identical adults.
But recall that these embryos were the product of (more or less) normal sexual reproduction. In other words, their moms and dads reproduced the old-fashioned way.
Not so with Dolly. (Her genetic mother, was actually Belinda's mother -- Dolly's grandmother. Likewise, Dolly's father was Belinda's father -- Dolly's grandfather). And assuming the technique works with other mammals, scientists suddenly have the capability to create countless copies of single adult animals, with no genetic input from other animals.
The difficult we do today...
Coming as it did from an animal researcher, the Scottish shocker was indeed a surprise to most scientists in the United States. "There were a million reasons to think it would not work, and only one to believe it would work," says Philip Leder, chair of the department of genetics at Harvard, "and they found that one. It's an unexpected feat, a major achievement."
Leder, who's also a Howard Hughes Medical Institute senior investigator, says Wilmut's crew jumped several apparent hurdles. The first was a simple transportation issue: "The genome is covered with an assortment of proteins that are very important for structure and regulation," he says. "To believe that [the genome] could be delivered intact without interfering with fundamental processes of the new cell" was a stretch of the imagination.
Furthermore, Leder says, "The genome is set up to work in the cell type from which it derived," yet it apparently worked fine in the egg cell -- and in the differentiating (defined) cells that eventually became Dolly.
Finally, some genes come in pairs -- one from each parent. These genes are regulated, or imprinted, so only one copy will make proteins (making proteins is what genes do for a living). Scientists had speculated, Leder observes, that, with this kind of cloning, "You might get expression of both sets," which could cause disease and death.
For more on one lucky lamb...
