Hello Dolly! What a Little Lamb Taught Us About Stem Cells

Hello Dolly! What a Little Lamb Taught Us About Stem Cells

She didn’t have a shirt pocket, so embryologist Karen Walker tucked the little container holding the tiny egg inside her bra to keep it warm on the chilly trip from the farm to the lab. 

It’s not unusual for it to be chilly in Scotland, but it is a bit odd to find a cell laboratory tucked in a corner of a Scottish sheep farm. “Lab” is a bit of a stretch: it was actually a cupboard, just big enough for two chairs and an incubator. 

Twenty-five years ago this month, Dolly the sheep was cloned from an adult sheep living on a farm near Edinburgh, Scotland. 

Dolly wasn’t just the first mammal ever cloned. Dolly was the first animal ever cloned from an adult cell of an existing animal. 

An egg from one of the farm’s Scottish Blackface sheep (the one carefully incubated by Walker), was brought into the tiny lab. In a delicate process, Walker and her partner, Bill Ritchie, removed the nucleus from the egg. Egg nuclei, like the nuclei of all cells, contain the DNA of the organism. 

Likewise, the researchers removed the nucleus from a breast cell taken from a second adult sheep, a white-faced Finn Dorset. The breast cell nucleus (containing DNA) was then inserted into the empty egg. 

Next, the researchers implanted the egg with the new DNA into a surrogate, another Scottish Blackface sheep. 

Nobody really expected success. Nobody was terribly confident that the DNA from an adult breast cell could be “reprogramed” to fashion the wide variety of cells found in an entirely new animal. 

But implantation was successful. The surrogate was pregnant. And at the end of a normal pregnancy, the surrogate gave birth to a healthy lamb.

Walker was away at a wedding at the time, so Ritchie sent a fax to her hotel:

“She has a white face and furry legs!” 

I bet the hotel staff thought: “Well….that’s a, umm, unique baby….”

Only the DNA donor was a whitefaced sheep. Both the surrogate and the (empty) egg donor were black-faced. 

Genetic tests would later confirm what appearances first revealed: Dolly was a clone of the sheep who donated the breast cell DNA. 

Dolly was a healthy ewe who went on to birth a total of six lambs. Dolly was euthanized at age six due to a lung disease she developed.

Following the announcement of Dolly’s birth, reaction ranged from the hopeful (“new cures for diseases!”) to the frightful (“oh no! armies of cloned humans!”). 

In reality, Dolly’s birth did not have much impact on animal cloning. Aside from the prize racehorse or prize cow here and there, cloning did not become a big deal.

Before Dolly, we thought that adult cells, once they had matured and developed into their final form (like heart cells, liver cells, nerve cells, etc.), were stuck in their final form and could not regress back to their unspecialized embryonic state. 

Dolly showed us that a specialized adult cell can be reprogrammed into an unspecialized embryonic cell. 

Unspecialized cells, capable of becoming any of the specialized cells in an animal’s body, are called “stem cells”, and stem cells are gold in medical research. 

Stem cells collected from actual human embryos are controversial and carry an unfortunate ethical stigma. 

But thanks to the Dolly research, cell biologist Shinya Yamanaka began developing stem cells from adult cells, a feat that won him a Nobel Prize in 2012. “Induced” stem cells have greatly reduced the need for ethically problematic embryonic stem cells. 

Because of her DNA origin in adult breast cells, researchers named Dolly (the sheep) for Dolly Parton (the singer). No disrespect for Ms. Parton was intended, according to the researchers, and Dolly Parton’s agent was said to respond: “There is no such thing as baaaaaaaaad publicity.”

Dolly is on display behind glass in the National Museum of Scotland – behind glass because people kept nicking bits of her wool. See the photo of me with the (second-most) famous Dolly! 

Dolly and her surrogate mom

Hello, Dolly!

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