In Memoriam: Dr. Ryuzo Yanagimachi, Cloning Pioneer

The University of Hawaiʻi at Mānoa John A. Burns School of Medicine mourns the loss of renowned scientist Dr. Ryuzo Yanagimachi, whose pioneering contributions to reproductive biology and cloning have impacted millions of people and allowed families to grow. Dr. Yanagimachi died on September 27, 2023, at 95.

Dr. Yanagimachi pioneered cloning and made numerous breakthroughs in mammalian fertilization and other fertilization techniques, like Intracytoplasmic Sperm Injection (ICSI). These techniques are used around the world in human infertility clinics.

Dr. Yanagimachi was born on August 27, 1928, in Hokkaido, Japan. He earned a Bachelor of Science in Zoology in 1953 and a Doctor of Science in Animal Embryology in 1960, both from Hokkaido University. The years after were marked by challenges, as he initially struggled to secure a research position, leading him to work as a high school teacher for two years. He would never forget this experience and actively assisted those he mentored.

In 1960, Dr. Yanagimachi's career brought him to the United States when he joined Dr. M.C. Chang at the Worcester Foundation for Biomedical Research. Here, he developed the techniques to fertilize hamster eggs "in vitro." This personal breakthrough would pave the way for the work and research Dr. Yanagimachi would conduct for the rest of his life.

In 1964, Dr. Yanagimachi returned to Hokkaido University as a temporary lecturer. Two years later, he'd arrive at the University of Hawaiʻi, a place he would ultimately call home. He started as an assistant professor at JABSOM's Department of Anatomy and Reproductive Biology.

Over his 38-year tenure and 18 years as Professor Emeritus, Dr. Yanagimachi's 57 combined years were marked with many breakthroughs recognized globally. 

In addition to his in vitro fertilization and intracytoplasmic sperm injection achievements, in 1997, at the age of 69, Dr. Yanagimachi cloned the world's first mouse. This groundbreaking research was published a year later in the journal Nature, detailing how he removed the nucleus from a somatic cell and injected it into an egg that also had its nucleus removed. The egg, bathed in a chemical solution and cultured, developed into an embryo, which was then implanted into a surrogate and allowed to develop. It is now known as the "Honolulu Technique."

The first mouse born through the Honolulu Technique was named Cumulina. It symbolized the incredible possibilities unlocked by Dr. Yanagimachi's pioneering work; the mouse is now in the Smithsonian in Washington D.C..

In 2000, Dr. Yanagimachi founded and directed the Institute for Biogenesis Research at the University of Hawaiʻi. The institute, devoted to studying embryogenesis, stem cell development, and transgenesis technology, would continue to push the boundaries of science. The faculty, staff, and students cloned the first male animal from adult cells.  In 2004, Dr. Yanagimachi’s team used ICSI techniques to  produce pups from an infertile male mouse. These achievements were critical moments in advancing research in human infertility. 

In 2005, Dr. Yanagimachi retired, but continued active research, though his passion for reproductive biology and cloning never waned. 

Our Associate Dean for Research, Dr. Mariana Gerschenson remembers Dr. Yanagimachi or “Yana” as we called him.  “He was an innovative scientist and a great mentor.  He was an inspiration to the faculty, staff, post-doctoral fellows, and students.  He will always be part of our ʻohana,” she said.

Throughout his illustrious career, Dr. Yanagimachi would also remember to pave the way for future scientists. Remembering his struggles breaking into the research field, Dr. Yanagimachi mentored and inspired up-and-coming researchers like Dr. Monika Ward.

"My journey began in 1999 when I moved from Poland to Hawaiʻi as a graduate student. I wanted to work in Dr. Yanagimachi's lab, but he didn't have a spot for me at the time. He encouraged me to write for fellowships and grants. After writing for four or five grants, he was impressed with my determination, and the following year, I got hired," she said. “Yana had a policy of giving his postdoctoral fellows two days a week to pursue their own ideas.  This encouragement to pursue other research venues resulted in the first cloned mouse by his postdoc Teruhiko Wakayama, who used the lab’s techniques to improve on cloning.” 

Dr. Ward is among the many mentored by Dr. Yanagimachi, who went on to become JABSOM faculty and would form their own lab. 

The current director of the IBR, W. Steven Ward, said that the IBR has flourished because of Dr. Yanagimachi’s initial leadership and continued example of excellence over the past 23 years of its existence.  “The IBR is populated by scientists who were trained by Yana, or recruited by him to join the work,” W. Steven Ward said. “ It is now a well established research institute world-renowned for its work on reproductive and developmental biology.  Throughout his tenure at the IBR he was a constant source of possible new projects and wealth of instant knowledge of the field.”

Dr. Yanagimachi received 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 honor. He was inducted into the National Academy of Sciences in 2001.

Most notably, Dr. Yanagimachi was honored this year with the Kyoto Prize, an international award presented to individuals who have made significant contributions to science and technology, as well as the arts and philosophy. Many compare it to the Nobel Prize. Dr. Yanagimachi was recognized in the Biotechnology and Medical Technology category for his significant contributions to the development of essential assisted reproductive technologies in modern society through both basic research and technological development. He was scheduled to accept the award in November 2023. When the Kyoto Prize was announced, Dr. Yanagimachi humbly said, "Although I was rarely directly involved in clinical investigations, I am very happy that some of the work we did played a role in bringing joy to many infertile couples."