The Mouse that Squeaked Its way into Scientific History

It was a sad day at the University of Hawaii Manoa's department of anatomy, reproductive biology.

The Mouse that Squeaked Its way into Scientific History

It was a sad day at the University of Hawaii Manoa's department of anatomy, reproductive biology. Cumulina, an old mouse, died naturally on May 5, 2000. Her birth had made international headlines. Ryuzo Yanagimachi was the principal investigator at the laboratory.

Cumulina, a cloned mouse born on October 3, 1997 was the first to successfully clone a mammal and the second mammal to be cloned from an adults cell. Her pioneering work in cloning animals was also a sign that it was possible. Dolly the Sheep was the first mammal to be cloned from an adult cells. Her birth occurred just 15 months later. This shock had inspired worldwide hope for biomedicine breakthroughs and raised ethical questions.

Dolly's success was complicated. Dolly was the only embryo that her Roslin Institute in Edinburgh cloned. To fuse the two, the team used a method that involved removing the nucleus of an egg cell from a Scottish Blackface sheep and electroshocking it using a mammary cell from a Finn Dorset lamb. The team then transferred the unusual egg cell, which contained a full complement DNA but had never been fertilized, into an ewe.

Roslin scientists continued to clone lambs and, in 1997, they created the first transgenic mammal from adult cells. Teruhiko Wakyama, one Yanagimachi's postdoctoral researches in Hawaii, had another idea.

Wakayama was inspired by Dolly's birth and spent time in the laboratory to try to create a mouse-clone. He took out the nuclei of egg cells and replaced them with nuclei taken form adult mouse cumulus cell nuclei. This is what normally plays a part in egg maturation. To test whether the eggs would succeed in giving birth, he then placed these eggs into surrogate female mice.

Wakayama and Yanagimachi made a miraculous result after a series of failed attempts to create a female mouse pup in fall 1997. After the cells that he used to create her, he named her Cumulina. Wakayama was internationally acclaimed for his achievements. Yanagimachi established the Institute for Biogenesis Research at University of Hawaii.

Wakayama, Yanagimachi created 84 more cloned mouse embryos in the year following Cumulina’s birth. This put to rest any doubts about whether or not cloning is possible. Wakayama's method was more efficient than that used by Roslin scientists to create Dolly. W. Steven Ward is the director of the University of Hawaii Institute for Biogenesis Research. "Cumulina was a significant breakthrough in the cloning technology."

Scientists have so far cloned over 20 species of animals. The most widely cloned animal in the world is the mouse that was created by nuclear transfer. However, not all of the most exciting scenarios about cloning that were presented in the 1990s have been realized. For example, researchers have yet to be able to replace the failing organ of a person with one made from cloned cells. However, the pioneering work of Dolly, Cumulina, and other cloned animal clones has led to advancements in stem-cell technology that allow scientists to explore regenerative medicine and investigate the causes of diseases such as diabetes, leukemia, and diabetes, and to develop new pharmaceuticals.

Although laboratory mice don't live to old age very often, Yanagimachi and his crew did everything they could to make Cumulina a long-lived creature. They even hosted birthday parties for Cumulina. Kristen Frederick Frost, curator of modern science at Smithsonian's National Museum of American History, says that "She was a pretty pampered mice."

Cumulina lived to be over 2 years old, which is the equivalent of nearly 90 years in human years. Yanagimachi kept her body in a freezer after her death until a teacher at a nearby high school offered to taxidermy it. Yanagimachi posed Cumulina with a block made of fake cheese. The stuffed mouse was displayed in Yanagimachi’s laboratory for a few years before it was moved to a closet. She was swept away by a flood in 2004 and since then has spent most of her time in storage.

Ward reached out to the National Museum of American History curators last year after Yanagimachi's retirement in 2005. Frederick-Frost states that accepting Cumulina was a simple decision. OncoMouse is also included in the collection. He was, with his successors and others, the first patentable genetically modified animal.

Editor's Note, May 25, 2022: This article now includes a more complete context of the experiments that led, among other things, to the Cloning of Dolly the Sheep.

This article is taken from Smithsonian magazine's June issue.