A Tribute to Sir Ian Wilmut

Dr. Ian Wilmut, famous for cloning the sheep Dolly at the Roslin Institute near Edinburgh Scotland, died last week.? I wanted to add my voice to tributes being paid to this humble and gracious scientist.?

??????????? ? The idea of organismal cloning – nuclear transplantation – goes back to the 1960s.? I remember reading the classic papers that had been published in 1962 where English scientist John Gurdon removed a cell nucleus from the intestinal epithelial cell of a tadpole and injected it into an egg cell.? The cytoplasm of the egg influenced the nucleus to reprogram to act like an egg nucleus rather than the nucleus of a differentiated (specialized) cell and to begin dividing.? The cells divided and then differentiated into all of the tissues needed to make a tadpole and then after metamorphosis, a frog.? This proved definitively that the nucleus of all differentiated cells contained all of the same genes, and that cell specialization was due to differential gene expression, using those genes differently to produce different proteins, rather than a mechanism where cells threw out this gene or that one.?

??????????? This research gave rise to multiple science fiction plots.? The book The Boys from Brazil (later a movie starring Laurence Olivier) imagined a plot where Dr. Mengele preserved some of Hitler’s blood and tissue and used it to clone dozens of baby Hitler’s; the plot was uncovered when assassins killed the fathers of the boys in an efforts to reenact the nurture of kids with his nature.? In an episode of Buck Rogers a group of space pirates plotted to kidnap Miss Universe (determined to be genetically perfect by DNA sequencing), played by the doomed Star 80 Dorothy R. Stratton, to sell her tissues on the black market as a source of nuclei for cloning.? A book published in 1977 called “In His Image” claimed that humans had been already been cloned and had been born.? No one believed the account.? The problem with these fictional stories was that no one could do it in real life.? No one could successfully clone a mammal.? After thirty years of trying the majority of scientists started to doubt that it could be done. ?????

??????????? Then Dr. Wilmut and his research partner, Keith Campbell, had a success cloning sheep using nuclei from embryos.? They produced Megan and Morag. (Dr. Campbell died in 2012.) ??Other teams cloned mice, but again, only with the nuclei from embryonic cells.? The question remained:? could anyone clone a mammal using adult cells?? Scientists became skeptical that it could be done.? Until Dolly.?

??????????? A ewe gave birth to Dolly on July 5, 1996 and this settled the controversy.? It could be done.?

??????????? Wilmut and Campbell had taken a nucleus from a mammary gland cell grown in culture.? They transplanted it into an egg cell and allowed that cell to divide in culture to produce a small embryo.? Then they transplanted the embryo into a surrogate ewe who had been treated with hormones to ready its uterus for transplantation.? It worked.

??????????? Three different breeds of sheep were used for each contribution.? A different breed was used for the cell line that donated the nucleus, for the egg donor, and for the surrogate ewe that incubated the embryo.? Dolly was the breed of the nucleus donor – proving success.??

??????????? While the above sounds so straight forward – it wasn’t. ?Again, no one had been able to pull it off for thirty years.? The team tried hundreds of eggs and had a single success.? They ?

Named the lamb born after Dolly Parton.? The joke was that this was the second most famous mammary gland tissue in the world.? (I’ve been told that the gracious Dolly Parton when asked about it said that she was flattered).? Dr. Campbell figured out that the nucleus had to be in a particular state, and he “starved” the cell line to place it in that state.? And even with this innovation, there were many, many failures.? But then, with Dolly, a success.?

??????????? Soon the organismal cloning of mammals became so common that you couldn’t make news cloning an single animal – you had to clone a menagerie and fill up a zoo with clones.? Cats, cows, dogs were cloned.? One business promise to clone your aging pet so that you didn’t have to say goodbye.? (There is a philosophical flaw in this reasoning, but it was business considerations that killed the idea rather than philosophical objections.). And we talked about this at Solano College, where my story really begins.? ?

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??????????? My colleague and Solano College partner-in-crime, Dr. Ed Re, came to me one day and said that he had invited Dr. Ian Wilmut to come to speak to Solano College students.? His wife, Dr. Martina Newell-McGloughlin (founder of the UC Davis biotechnology program and former University of California systemwide biotechnology program director) knew him well and arranged an introduction.? Since Dr. Wilmut’s parents had been teachers, so he had a special place in his heart for students, and during a trip to California he was willing to come to Solano College to give a lecture.? He agreed to waive his typically speaker’s fee of tens of thousands of dollars.?

??????????? He gave his lecture and the spent hours talking with students.? The lecture was not on Dolly, per se, but on the basic science of cell differentiation and where the field stood and where the field was going.? Students peppered him with questions. After taking pictures, I took over and drove him to neighboring Napa.? I thought that his generosity at waving the speaker’s fee and his generosity with his time - spending so much time with our students - should at least be rewarded with a quintessential California experience.? I didn’t foresee that this day would become one of the most epic adventures of my life and that of some of my friends.?

??????????? ??? So I drove him to Napa and took him to my favorite Mexican restaurant there.? I reasoned that California Mexican food would surpass another available in Scotland.? We talked science, and about Scotland, and about England, and I told him about Solano College.? But I had arranged a Napa Valley wine experience.??

??????????? My friend Nicki Pruss was head winemaker at the Stag’s Leap Wine Cellars, one of the most respected wineries in Napa – or in California – or in the world.? (Stag’s Leap Wine Cellars was one of the two wineries that put California on the international wine map in 1976 in the Judgment of Paris – refer to the movie “Bottle Shock.”). ?It was Fall, and Crush was on, and Nicki took us into the vineyard in a pickup truck to sample grapes from different rows.? Nicki has one of the best palates in California and tried to get us to dissect the different flavors contained within the grapes and to try to get us to discern the subtle differences in a grape grown in the middle of a row and at the end of a row.? “This is why you sample at different places in the vineyard,” she told us.?? ??

??????????? We then went into the Stag’s Leap wine cave to sample wine whose fermentation was in progress.? Nicki used a “wine thief” to pull a sample out of the barrel and took us through the winemaking process.? We then went into the laboratory where we tasted wine samples of Stag’s Leap bottles of wine.? Then my friend and noted bon vivant Chris Demetre arrived.? I expected the evening to end there.?

??????????? Chris and Nicki were headed to an industry wine tasting hosted by the Napa Wine Vintners.? It was being hosted at Bottega, noted Napa chef Michael Chiarello’s new restaurant that was opening that night. Sir Ian and I tagged along.?

??????????? The top wine makers in Napa were there.? Over the course of the next few hours, different vintners poured the most exclusive bottles of wine in Napa into his glass.? (These wines usually sold for several hundred dollars a bottle).?? Michael Chiarello’s dashing self came by with his special prosciutto.? Okay, wow, that was fortuitous.? Very few people figured out that Dr. Ian Wilmut was in the house, but those that did asked the questions that I didn’t have the guts to ask.?

??????????? “It’s Sir Ian.? Have you met the queen?”

??????????? “Which time would you like to know about?”

??????????? “I’m a republican partially to spare that poor woman having to shake hands with an endless line of people for hours and hours.”

??????????? “You cloned Dolly.? Can you clone me a new liver?”

??????????? “We are in the basic research stage right now, discovering fundamental knowledge.? That’s not really what I’m doing?”

??????????? “Are you going to win a Nobel Prize?”

??????????? “There’s a chance.? But there are politics, and things have to fall just right for it to happen.”? ?

??????????? OK, well, that was fortuitous timing being invited to the exclusive wine event, but NOW it’s time to go.? After this event was the long anticipated launch of the trendiest and newest restaurant in Napa.? Reservations had been made months in advance.?? There’s no way that we could…but then we were invited.???

??????????? I remember that dinner was spectacular.? Chef Michael Chiarello came by our table and served us perfect gnocchi.? ??Sitting at our table was Steve Lawrence, a brit with a British sense of human, that used to work Stag’s Leap Wine Cellars. When it came time for Sir Ian to order Steve cheekily replied,” he’ll have the lamb!” Sir Ian was gracious and laughed heartily.? That was quite an event, and it ended quite an adventurous day – for everyone.? That whole experience was quite serendipitous or should I say Sir Ian-dipitous.? (Sorry).

??????????? I had expected an early evening, but I ended up dropping him off at his hotel in San Francisco at 2 AM.?

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??????????? In the end the Nobel Committee did not include him in the Nobel Prize.? In 2010 the Nobel Prize that would be devoted to cloning went to John Gurdon (who performed the original cloning) and Shinya Yamanaka (who first produced induced pluripotent stem cells). ?Those awards were well deserved, but I was hoping that one of the nicest and most humble scientists that I had ever met would share the Prize with the third position.

??????????? Later, being the gracious gentleman that he was, Dr. Wilmut sent me the nicest Thank You note.?

??????????? It was a privilege to have spent time with him, and to have this adventure, and I’ll always be grateful for the way that he interacted with our students.?

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??????????? At dinner in Napa, he did indeed order the lamb.?

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