Ryuzo Yanagimachi
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was a Japanese-born, American-based scientist. He made numerous key contributions to the study of mammalian fertilization, and he was also a pioneer in the
cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
field. Accordingly, he assisted in fertilization technologies such as ''in vitro'' fertilization and direct sperm injection into the egg (commonly called
intracytoplasmic sperm injection Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embr ...
or ICSI), which are widely used today in human infertility clinics throughout the world. In 1997, his laboratory at the
University of Hawaiʻi at Mānoa The University of Hawaii at Mānoa is a Public university, public Land-grant university, land-grant research university in Honolulu, Hawaii, United States. It is the flagship campus of the University of Hawaiʻi system and houses the main offic ...
successfully cloned
mice A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
using the Honolulu technique.


Biography

Yanagimachi was born in
Ebetsu is a Cities of Japan, city in Ishikari Subprefecture, Hokkaido, Japan. History Ebetsu was settled originally by Japanese people in 1871, who came from the Miyagi Prefecture on Honshu. In 1878, tondenhei began moving into the area. When the M ...
and raised in
Sapporo is a Cities designated by government ordinance of Japan, designated city in Hokkaido, Japan. Located in the southwest of Hokkaido, it lies within the alluvial fan of the Toyohira River, a tributary of the Ishikari River. Sapporo is the capital ...
, Japan. He received a BS in
zoology Zoology ( , ) is the scientific study of animals. Its studies include the anatomy, structure, embryology, Biological classification, classification, Ethology, habits, and distribution of all animals, both living and extinction, extinct, and ...
in 1952 and a DSc in animal
embryology Embryology (from Ancient Greek, Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, ''-logy, -logia'') is the branch of animal biology that studies the Prenatal development (biology), prenatal development of gametes (sex ...
in 1960, both from
Hokkaido University , or , is a public research university in Sapporo, Hokkaido, Japan. Founded in 1918, it is the fifth-oldest government-authorised university in Japan and one of the former Imperial Universities. The university finds its roots in Sapporo A ...
. Being unable to find a research position initially, he then worked as a high school teacher for two years. Yanagimachi applied for a
post-doctoral A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary academ ...
position with Dr. M. C. Chang of the
Worcester Foundation for Biomedical Research The Worcester Foundation for Biomedical Research (WFBR) was a non-profit biomedical research institute based in Shrewsbury, Massachusetts, United States. History The foundation was established as an independent research center under the name Worces ...
in Shrewsbury, Massachusetts. He got this position and there discovered how to fertilize hamster eggs ''in vitro''. This work led to ''in vitro'' fertilization of eggs of humans and other mammalian species. In 1964, he returned to Hokkaido University as a temporary lecturer, with the possibility of later being appointed to an assistant professorship. However, another person eventually got the position. In 1966 Yanagimachi ended up at the University of Hawaiʻi as an assistant professor and became a full professor of the Department of Anatomy and reproductive biology at the John A. Burns School of Medicine. After working for 38 years at the University of Hawaii, he retired at the end of 2005 to become a
professor emeritus ''Emeritus/Emerita'' () is an honorary title granted to someone who retirement, retires from a position of distinction, most commonly an academic faculty position, but is allowed to continue using the previous title, as in "professor emeritus". ...
but kept working with junior fellows. He was married to Hiroko, a former child psychologist. She could not find work in her field when they came to the U.S. due to a language barrier, so she went to work with researchers in his lab as an electron microscopist. Ryuzo Yanagimachi died in Honolulu from complications of a fall on September 27, 2023, at the age of 95.


Cloning

In July 1998, Yanagimachi's team published work in ''
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' on cloning mice from adult cells. Yanagimachi named the new cloning technique they had created to do this to work the "Honolulu technique". The first mouse born was named Cumulina, after the cumulus cells whose nuclei were used to clone her. At the time of the publication of this work, over fifty mice spanning three generations had been produced through this technique. This was accomplished by an international team of scientists, including co-authors Teruhiko Wakayama, Tony Perry, Maurizio Zuccotti and K.R. Johnson. The Yanagimachi laboratory moved from the warehouse which had housed it for over thirty years into the newly created Institute for Biogenesis Research in the Biomedical Sciences Tower of the John A. Burns School of Medicine. Money and renown from the opportunities opened up by the ''Nature'' article made the institute possible. The Yanagimachi laboratory and his former associates continued to make advances in cloning. The first male animal cloned from adult cells was announced in 1999. In 2004 the laboratory participated in the cloning of an infertile male mouse. This advance may be used to produce many infertile animals for use in research on human infertility. Mice cloned by the Honolulu technique were displayed at the
Bishop Museum The Bernice Pauahi Bishop Museum, designated the Hawaii State Museum of Natural and Cultural History, is a museum of history and science in the historic Kalihi district of Honolulu, Hawaii, Honolulu on the Hawaiian island of Oʻahu. Founded in 1 ...
in Honolulu, Hawaiʻi, and the Museum of Science and Industry in Chicago, Illinois.


Major work before and after 1960

As a graduate student of
Hokkaido University , or , is a public research university in Sapporo, Hokkaido, Japan. Founded in 1918, it is the fifth-oldest government-authorised university in Japan and one of the former Imperial Universities. The university finds its roots in Sapporo A ...
in Japan, Yanagimachi studied fish (herring) fertilization and the sexual organization of
rhizocephala Rhizocephala are derived barnacles that are parasitic castrators. Their hosts are mostly decapod crustaceans, but include Peracarida, mantis shrimps and thoracican barnacles. Their habitats range from the deep ocean to freshwater. Together w ...
ns (parasitic barnacles). In fish, he discovered calcium-dependent,
chemotactic Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
movement of spermatozoa into the micropyle through which the fertilizing spermatozoon enters the egg. This was the first discovery of sperm chemotaxis in vertebrate animals. In rhizocephala, he found that adults are not hermaphroditic as generally thought, but bisexual. The so-called "testis" in an adult animal is a receptacle of cells from larval males. This discovery revolutionized biological studies of rhizocephalans and related animals. While he was at the
Worcester Foundation for Biomedical Research The Worcester Foundation for Biomedical Research (WFBR) was a non-profit biomedical research institute based in Shrewsbury, Massachusetts, United States. History The foundation was established as an independent research center under the name Worces ...
as Dr. M.C. Chang's postdoctoral fellow (1960-1964), he witnessed and recorded the entire process of sperm penetration through the
zona pellucida The ''zona pellucida'' (Latin meaning "transparent zone") is the specialized area surrounding mammalian oocytes (eggs). It is also known as an egg coat. The ''zona pellucida'' is essential for oocyte growth and fertilization. The ''zona pelluc ...
and fusion with the egg proper in a living (
hamster Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera. They have become established as popular small pets. The best-known species of hamster is the golden or Syrian ...
) egg, which was the first in mammals. He was one of few who began to study the process and mechanisms of mammalian fertilization using ''in vitro'' fertilization technique. Throughout his career he has made numerous, fundamental contributions to our understanding of mammalian fertilization and to the development of assisted fertilization technologies such as
in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating the ovulatory process, then removing an ovum or ova (egg or eggs) from ...
(IVF) and
intracytoplasmic sperm injection Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embr ...
(ICSI) which are widely used today in human infertility clinics throughout the world. His comprehensive review of the basic biology of "Mammalian Fertilization" published in 1994 (In: Physiology of Reproduction, Knobil & Neill eds,
Ravan Press Ravan Press, established in 1972 by Peter Ralph Randall, Danie van Zyl, and Beyers Naudé, was a South African anti-apartheid publishing house.
) is classic. Yanagimachi himself considered "cloned mice" to be byproducts of fertilization study and that the production of cloned animals in various species triggered/accelerated the research on the genomic reprogramming of adult somatic (body) cell nuclei as well as the production of
pluripotent stem cells Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, ...
from adult cells for therapeutic purposes. He retired in 2005, but continued working on natural and assisted reproduction. In 2014, he had an interview with ''The Prism'' in which he was quoted saying:
Unlike people, nature never lies.


Awards and honors

*
Fulbright Scholarship The Fulbright Program, including the Fulbright–Hays Program, is one of several United States cultural exchange programs with the goal of improving intercultural relations, cultural diplomacy, and intercultural competence between the people ...
, US-Japan, 1960 and 1964 *Lalor Foundation Scholarship, US, 1964–1966.
Zoological Society Prize
Japan, 1977 *Research Award, Society for Study of Reproduction, US, 1982 *University of Hawaii Regents' Medal for Excellence in Research, US, 1988 *Recognition Award, Serono Symposia, US, 1989 *Marshall Medal, Society for the Study of Fertility, UK,1994 *
International Prize for Biology The is an annual award for "outstanding contribution to the advancement of research in fundamental biology." The Prize, although it is not always awarded to a biologist, is one of the most prestigious honours a natural scientist can receive. Ther ...
, Japan, 1996 *Honorable Degree of Philosophy from the University of Rome, Italy, 1997 *Distinguished Andrologist Award, American Society of Andrology, US, 1998 *Induction to the Polish Academy of Sciences, Poland, 1998 *Carl G. Hartman Award, Society for the Study of Reproduction, US, 1999 *Honorable Degree of Philosophy,
University of Pavia The University of Pavia (, UNIPV or ''Università di Pavia''; ) is a university located in Pavia, Lombardy, Italy. There was evidence of teaching as early as 1361, making it one of the List of oldest universities in continuous operation, oldest un ...
, Italy, 1999 *Honorary Member,
European Society of Human Reproduction and Embryology The European Society of Human Reproduction and Embryology (ESHRE) was founded in 1985 by Robert Edwards (University of Cambridge) and Jean Cohen (Paris), who felt that the study and research in the field of reproduction needed to be encouraged and ...
, 1999 *Pioneer Award, International Embryo Transfer Society, 2000 *Induction to the National Academy of Sciences, US, 2001 *Honorable Degree of Philosophy, Hokkaido University, Japan, 2002 *Induction to Hall of Honor,
National Institute of Child Health and Human Development The ''Eunice Kennedy Shriver'' National Institute of Child Health and Human Development (NICHD) is one of the National Institutes of Health (NIH) in the United States Department of Health and Human Services. It supports and conducts research ai ...
, US, 2003 *Donald Henry Barron Lecture,
University of Florida The University of Florida (Florida or UF) is a public university, public land-grant university, land-grant research university in Gainesville, Florida, United States. It is a senior member of the State University System of Florida and a preem ...
, US, 2003 *Pioneer Award in Reproduction Research, US, 2012 *Lifetime Achievement Award, Society of Reproductive Biologists and Technologists, US, 2014 *
Kyoto Prize in Advanced Technology The Kyoto Prize in Advanced Technology is awarded once a year by the Inamori Foundation. The Prize is one of three Kyoto Prize categories; the others are the Kyoto Prize in Basic Sciences and the Kyoto Prize in Arts and Philosophy. The first Kyo ...
, Japan, 2023


References


External links


Museum of Science and Industry exhibit containing cloned mice

"Heads or Tails?" article
in ''The Prism'', UH Mānoa's e-newsletter on international education {{DEFAULTSORT:Yanagimachi, Ryuzo 1928 births 2023 deaths Members of the United States National Academy of Sciences Members of the Polish Academy of Sciences Japanese scientists Hokkaido University alumni People from Ebetsu, Hokkaido Scientists from Hawaii People from Sapporo University of Hawaiʻi faculty John A. Burns School of Medicine faculty Japanese emigrants to the United States Kyoto laureates in Advanced Technology Hawaii people of Japanese descent