First test-tube rhesus monkey healthy and virile after 15 years

Fifteen-year-old Petri, the world’s first test-tube rhesus monkey, at the Primate Research Center.

If there is a crystal ball for the estimated 300,000 people in the world whose lives began with the help of in-vitro fertilization (IVF), it exists in the furry form of Petri, a 25-pound rhesus macaque still living at UW–Madison.

Fifteen years ago this Aug. 24, Petri, aptly named for the glass dish in which he was conceived, was born in a blaze of publicity and anticipation, the world’s first test-tube rhesus monkey. Arriving nearly five years after the birth of Louise Brown, the first human born through the technique of in-vitro fertilization, Petri was hailed as a critical model, a window to the future health and fecundity of humans born through the then-revolutionary method of uniting egg and sperm in a test-tube.

Today, Petri still resides in the laboratory where he was conceived and born at the Wisconsin Regional Primate Research Center. And the good news, according to Barry Bavister, the pioneering reproductive physiologist who brought Petri into the world, is that Petri is by all measures a completely ordinary and healthy monkey.

For the hundreds of thousands of people whose lives began through IVF, Petri’s unremarkable existence should be a source of comfort, said Bavister.

“The primary thing is his normality. It allays fears that somewhere down the road there would be problems,” he said, referencing nagging concerns that somehow humans conceived through IVF, while seemingly normal at birth, might face developmental or reproductive problems later in life.

In Petri, and two other male rhesus macaques conceived through IVF at the Wisconsin primate center, normal is the operative word, however. All have matured through puberty and sired, through traditional means, healthy offspring.

Although humans born through in-vitro fertilization arrived on the scene years before the primate model, the compressed lifespans of non-human primates make it possible to study mileposts of development and reproduction that IVF humans have yet to encounter. The average lifespan of rhesus macaques is 26, but those in captivity may live to be 40.

“Monkeys mature so much faster than humans,” said Bavister. In addition, rhesus macaques and humans, at the genetic level, are nearly the same, sharing a genome that is more than 90 percent identical.

The IVF rhesus monkey model is extremely important, according to Richard Rawlins, director of the In-Vitro Fertilization/Assisted Reproductive Technology Laboratories at Rush Presbyterian-St. Luke’s Medical Center in Chicago. In terms of development and our ability to understand the early embryo, the rhesus monkey is our safest bet, he said.

“The rhesus monkey model is excellent in the culture dish as well as in terms of our understanding of the first phases of development. It is the best model for human perinatal physiology,” said Rawlins.

The fact, too, that Petri and his two test-tube companions at the Wisconsin primate center have successfully reproduced may help allay lingering concern about the future reproductive success of humans conceived through IVF.

“It’s a potential concern and an open question,” said Rawlins, “We don’t really know.”

Another important upshot of the IVF work in non-human primates is the potential to open a floodgate of new knowledge about early embryonic development. Because federal support to study human embryos is proscribed, there is a vacuum of knowledge about embryonic development in people. Rhesus monkeys, according to Rawlins and others, offer the best alternative.

Even so, rhesus embryos are difficult if not impossible to obtain. Only two labs in the U.S., the Wisconsin Regional Primate Research Center and the Oregon Regional Primate Research Center are routinely conducting the difficult and labor-intensive task of culturing rhesus embryos in the lab. As a result, developmental biologists, including the human IVF community, are gaining most of their insight into early embryonic development from mice and cattle.

“If you want to see what will be happening (in human IVF) in 10 years, you have to look at the cow,” Rawlins said. That circumstance, he argues, is far from ideal because cattle and rodents, genetically and developmentally, are much different than humans: “The reality is that rhesus monkeys offer a lot more potential about what’s happening with humans than the mouse or the cow. But getting rhesus embryos is the big problem.”

That logjam could be broken, said Bavister and Rawlins, if the technology that brought Petri into the world could be expanded to produce large numbers of embryos. Successfully combined with other technologies, such as cryogenic storage, the supply of rhesus embryos for research could be dramatically increased. The technology to help make that happen, cryopreservation, for example, is being refined at a number of laboratories, including the Yerkes Regional Primate Research Center.

Rawlins argued, too, that such technology holds potential for preserving endangered primates. Seventy-five percent of the primate order is endangered, he said.

“It is a really great thing in terms of conservation of animals. You can bank the eggs, you can bank the sperm” and, theoretically, you could use fairly common rhesus monkeys as surrogates to carry the implanted embryos of endangered primates to term.

“From the standpoint of the conservation of endangered animals, it’s very important,” Rawlins said.