November 4 might have been Dolly Day on campus as MIT students, faculty and friends gave a celebrity's welcome to Ian Wilmut, the Scottish creator of Dolly the sheep -- the world's only animal cloned from the cell of an adult donor.
Eagerly anticipating a scientific insider's view of the famous white ewe, students pounded up the stairs in Rm 10-250 chanting fragments of "Hello, Dolly," the Broadway show tune. Professor Phillip A. Sharp, head of the Department of Biology, referred to a new English word, "Dollymania," in his opening remarks. The hall was full to overflowing before Dr. Wilmut, a scientist at the Roslin Institute in Edinburgh, appeared at the lectern.
"Nuclear transfer technology is clearly a robust technique," Dr. Wilmut said as he recounted the research and technique that produced Dolly.
Dr. Wilmut's hour-long lecture balanced technical charts detailing nuclear transfer technology with a step-by-step narrative of exactly where Dolly came from, illustrated with color slides of Dolly being cuddled by two children, Dolly with her mother, and a herd of lookalike (but not cloned) sheep in a Scottish barnyard.
Dr. Wilmut cited some limitations of nuclear transfer, including its inefficiency, the high death rate of lambs, and increased birth weight among those that are born (known as large offspring syndrome). He predicted improvements in the technology, including use of other donor cell types and replication of nuclear transplantation in other species such as cattle, rabbits and perhaps humans.
On a slightly futuristic note, the geneticist suggested advances in biotechnology that might arise from Dolly's success. Dr. Wilmut mentioned gene targeting, which would enable scientists to make changes to specific genes (such as those carrying mitochondrial diseases) and to regulate genetic expression.
Applications of gene targeting also include development of pharmaceutical proteins and xenotransplantation (cross-species organ transplants, such as from pigs into humans). Xenotrans-plantation would entail altering pig organs to make them acceptable in humans, whose immune systems will otherwise destroy the alien organs.
"More than 160,000 people have died in the developing world due to lack of organs for transplant," Dr. Wilmut said.
Gene targeting could aid biomedical research, he said, most clearly in diseases such as cystic fibrosis, which results from a defect in just one gene, and eventually Parkinson's disease and leukemia.
Gene targeting to cure cystic fibrosis would require manipulating cells in a living sheep, and cell-based therapy for Parkinson's disease and leukemia would require "going back to an embryo state" to correct a mutation in the cell by literally "re-growing" it.
Using this powerful technology to make sheep sick or to make a living entity whose only purpose is cell production is "deeply offensive to some people," Dr. Wilmut acknowledged to the silent crowd.
Speaking in a steady, affable tone, Dr. Wilmut raised and then responded to some of the most provocative and controversial issues in the field of genetics in general and cloning in particular.
To do this, he first summarized some of the inquiries his team had received about the potential applications of nuclear transfer technology. These included overcoming infertility for men lacking sperm or for gay and lesbian couples; recovering lost relatives, especially teen-aged children; and producing "selected" children.
He then commented on the depth of pain and loss endured by parents whose children had died, but added that since personality is "one-half genetics and one-half environment, lost relatives really cannot be recovered." On the subject of genetically selected children, Dr. Wilmut said, "Each child should be treated as a unique individual."
As for the regulation of cloning and the potential commercial uses of nuclear transplantation, Dr. Wilmut said in a gently chiding tone, "In the US you all have such anxiety about big government, but why don't you have anxiety about big commerce? In this country there might be no need to go offshore" to replicate humans through cloning.
The event ended on an upbeat note, at least for geneticists. The final questions -- what of Dolly's progeny? Will there be any? Will they be normal? -- seemed to inspire Dr. Wilmut all over again, for he smiled as he announced that his unique ewe would be mated with a commercially bred ram in the coming months.
"As you remember, sheep-breeding season runs from now through February. Dolly is just now old enough to breed. We'll know more about her next spring."
A version of this article appeared in MIT Tech Talk on November 12, 1997.
