Ryuzo Yanagimachi

Ryuzo Yanagimachi (born August 27, 1928, Sapporo, Japan—died September 27, 2023, Honolulu, Hawaii, U.S.) was a Japanese-born American scientist whose team cloned the second live mammal, a mouse, and was the first to produce successive generations of clones.

Yanagimachi attended Hokkaido University in Sapporo, earning a bachelor’s degree in zoology in 1953 and a doctorate in animal embryology in 1960. Unable to find a research position in Japan, he applied for and received a four-year postdoctoral fellowship at the Worcester Foundation for Experimental Biology in Shrewsbury, Mass. While there he conducted experiments on golden hamster eggs that provided the groundwork for the in vitro fertilization (IVF) of human eggs, later accomplished by another research group in 1969. Yanagimachi returned to Japan in 1964 to teach at Hokkaido University, but in 1966 he accepted a position as an assistant professor at the University of Hawaii’s John A. Burns School of Medicine. He was appointed professor of anatomy and reproductive biology there in 1974. His wife, a child psychologist, joined him at the laboratory, where he trained her as a microscope technician.

Yanagimachi was among the first embryologists to study the acrosome reaction, the process by which a sperm penetrates the zona pellucida, allowing it to bind to the plasma membrane of an egg. He determined in 1970 that only sperm that had undergone the reaction could bind to the plasma membrane. A 1976 study conducted by his team showed that hamster eggs from which the zona pellucida had been stripped could fuse with acrosome-reacted sperm from other species, allowing the development of the human sperm penetration assay, which could aid in determining human fertility potential. In 1976 Yanagimachi and his team also performed the first mammalian intracytoplasmic sperm injection (ICSI), a process whereby a sperm nucleus is injected directly into an egg cell.

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Yanagimachi’s experience observing the behaviour of reproductive cells culminated in 1998 in another breakthrough when he and his team of researchers produced more than 50 mouse clones, including 2 successive generations of clones from the original clone. The Honolulu technique, so named to distinguish it from the less-efficient method used to produce Dolly the sheep (see nuclear transfer), used cumulus cells, which were injected directly into an enucleated egg cell. The next year the team created the first clone of an adult male mammal—a male mouse—and developed a new method using freeze-dried or detergent-treated sperm to deliver genes from one type of animal to another. The new method for genetically modifying animals using treated sperm was dubbed Honolulu transgenesis. By 2004 the team had cloned an infertile mouse incapable of producing sperm, which had implications for the treatment of human infertility.

In 2000 Yanagimachi founded the Institute for Biogenesis Research at the University of Hawaii. The institute, devoted to studying embryogenesis, stem cell development, and transgenesis technology, was funded by the National Institutes of Health as well as by private donations. Yanagimachi directed the institute until 2004 and continued teaching until becoming emeritus in 2006. His work earned him numerous awards, including the 1996 International Prize for Biology, Japan’s highest scientific award, and the 1999 Carl G. Hartman Award, the Society for the Study of Reproduction’s greatest honour. He was inducted into the National Academy of Sciences in 2001.