Fertility and Cloning

With sincere humility, he considered himself ‘mediocre’ but his willingness to ask ‘stupid questions’ led to an important scientific breakthrough. 

FAMILY BACKGROUND

Ryuzo Yanagimachi (RY) was born in Ebetsu, a city on the Japanese island of Hokkaido. His father owned a post office; his mother was a homemaker. RY grew up in Japan, where he was a good student, especially interested in science. 

EDUCATION

RY attended the University of Hokkaido, where he received a Bachelor’s degree in zoology and a Doctorate in animal embryology. 

FIRST JOB – MAYBE NOT EASY TO FIND AND NEVER A BINDING COMMITMENT

Despite being a model student, RY despaired of finding an academic job in his specialty, aquaculture; at the time, Japanese universities were ‘clubby’ and opaque (opposite of public disclosure of the reasons for their hiring and promotion decisions), with jobs often being given, unannounced, to preselected candidates. So, RY looked abroad and found a postdoctoral position in biomedical research in the U.S., specifically in Massachusetts. 

PERSISTENCE, PERSISTENCE! 

Although RY’s background was in fish fertility, he ended up working primarily with mammals, in particular with hamsters. In his first few years he pioneered ‘in vitro fertilization’ techniques, advances that made possible the human I.V.F. revolution of the 1980s. 

With his fellowship in Massachusetts ending, RY tried to return to Japan but once again found himself shut out of being offered any academic positions related to his professional resume and experience. So, he accepted a position at the University of Hawaii and remained there for the rest of his career. 

RY’s long career as a pioneer in fertility research culminated with the successful cloning of multiple generations of mice – a leap ahead of the announcement of the first cloned mammal, “Dolly” the sheep, just months earlier. 

At the time of RY’s announcement, he was already nearing retirement. RY and his team at the U of Hawaii had successfully cloned not just one mouse but dozens, across multiple generations. 

“Dolly,” the result of work by Ian Wilmut of Scotland, still dominated the scientific and general news but in many ways, it was RY’s work that was the real scientific breakthrough. Dr. Wilmut and his team had used a procedure that essentially starved an adult cell to the point where it went into hibernation, then removed the nucleus of an embryonic cell and replaced it with that of the starved cell. It was, Wilmut admitted, a crude process that took hundreds of attempts to get right. 

In contrast, RY used an apparently less complex technique, developed with one of his postdoc students. Instead of starving an adult cell into hibernation, they looked for cells that were already in that state naturally. They settled on ‘cumulus’ cells, which surround the egg.

He named the first mouse, a female, “Cumulina”; by the time he and his team announced their work, they had nearly 70 specimens, all females. Seven were even clones of clones, something previously thought unimaginable. Overall, the so-called ‘Honolulu technique’ achieved a success rate of between 2 and 3 percent, significantly better than Dr. Wilmut’s. 

RY’s work showed that Dolly was not, as many scientists had suspected, a fluke. Later, RY and his team announced that they had cloned a male mouse. 

CHALLENGE – POSSIBLE DANGEROUS FUTURE USES OF YOUR WORK

After cloning the male mouse, it seemed as if cloning was not just the future but increasingly, the present. RY, however, was skeptical. He always said his work on cloning was a byproduct of his other fertility research and he warned that cloning, especially human cloning, was dangerous and morally fraught. 

“If all the humans on the face of the earth were infertile,” said RY, “This may be justified. But until then we should stick to reproduction the way that Mother Nature did it for us.”

CAREER SATISFACTION

Util his cloning breakthrough made him a celebrity, RY labored in a converted warehouse on a corner of the U of Hawaii campus. His work ethic was famous among fertility researchers worldwide; he was in his lab 12 hours a day or more, seven days a week, for decades. (His wife had died and they had no children.)

Thanks to funding opportunities that poured in after the announcement, RY was able to found the Institute for Biogenesis Research at the university’s school of medicine. 

RY was a member of the National Academy of Sciences and received the Kyoto Prize, Japan’s highest private honor for his work. Still, he remained modest about his achievements. 

“I consider myself mediocre,” he said in an interview with the journal Andrology. “The only thing I know of myself is that I like asking stupid questions. Nine out of 10 questions I made and continue to make were / are stupid or nonsense. Yet one of out 10 proved to be good.”

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This career story is based on several sources, including an obituary written by Clay Risen, published by The New York Times on October 18, 2023 plus internet research.