Researchers at the Chinese Academy of Sciences have produced healthy mice from two mothers that were then able to have healthy offspring themselves. The research published today in Cell Stem Cell, aimed to discover why it is so challenging for animals of the same sex to reproduce, showing that stem cells and gene editing may be able to overcome these barriers.
Researchers in China have created healthy mice from two female parents. Why did they do it and could this lead to a way for gay and lesbian couples to have biological children together?Leyun Wang
This, may at first glance seem like an unusual topic to research, but several animals already have what would be considered unusual methods of reproduction by human standards. For example, some reptiles, amphibians and fish can reproduce by themselves (asexually) and several species of fish can actually change their sex and then reproduce as the opposite sex to how they were born. Some humans are also already experimenting with unusual ways of mammalian reproduction, by cloning their dead pets via ethically and scientifically questionable methods.
"Although animals have 3 different reproduction modes, termed as asexual reproduction, unisexual reproduction and sexual reproduction, mammals can only undergo sexual reproduction. We were interested in the question of why mammals can only undergo sexual reproduction." said Qi Zhou, a senior author of the paper.
Previous work created mice from two mothers, but the offspring was unhealthy. The researchers hypothesized that this was due to a genetic process called imprinting; a way in which certain genes in the DNA genetic code are branded with a molecular stamp, identifying which parent they came from.
The study used embryonic stem cells (ESCs), which were haploid meaning that they only have half of the genetic material of normal cells in the body, the same amount as sperm and egg cells typically used for mammalian reproduction. Crucially, the researchers used gene editing to delete three imprinted regions of the genome, before injecting these ESCs into the eggs from a different female mouse and developing them into embryos. From 210 embryos they were able to produce 29 live mice, which developed normally and were able to live to adulthood, ultimately producing offspring of their own.
The team also tried to create offspring from two male mice using a similar gene editing method, but the mouse pups were unhealthy and died after just a couple of days.
"There may be some important unknown imprinted regions that need to be modified for the survival of bipaternal mice. We are planning to dissect the necessary imprinting modifications that can support the survival of bipaternal mice to adulthood," said Wei Li, another senior author of the work.
Previously, researchers in Japan were able to make cells from an adult mouse into eggs by first turning them into induced pluripotent stem cells (iPSC), a method which is now mainstream in research laboratories around the world after John B. Gurdon and Shinya Yamanaka won the Nobel prize for the work in 2012. Creating sperm and egg cells from adult human cells is a hot research topic that many companies and research groups are currently pursuing.
Although this work is likely to be met with claims of 'meddling with nature' and hysteria there are several scientific reasons to do this work.
"One reason is to understand better how fertilization and embryonic development work. That could help understand and prevent some forms of infertility, as well as understanding (perhaps) the origins of some congenital diseases," said Hank Greely, Director of the Center for Law and the Biosciences and Professor of Law at Stanford University.
There will also be some hoping that this new work further builds towards the possibility that gay and lesbian couples may one day be able to have their own biological children, although there is still a long way to go before showing that these results in mice might be possible in humans. One reason being that there are differences in imprinting between mice and humans, meaning human cells may need different manipulation to that shown in the recent study.
"It might. It might not - biology is tricky - but it does open a plausible route. It’ not the only conceivable (so to speak) route - my book lays out a simpler route of directly making eggs from cells from the bodies of men and sperm from the bodies of women, but that method has never been demonstrated in mice. This one has," said Greely.
This kind of research in mice is currently permitted in the U.S., although Greely claims it would be unlikely that federal funding would be permitted for similar work on human embryos. However, it is not currently strictly forbidden up to the point where the human embryo would be implanted for pregnancy and possible birth. This requires FDA-approval and is likely to be a long and difficult journey for anyone who wishes to try to gain it in the future.
"There would need to be a decade or more of safety testing before the FDA-approved such a process in humans - and that’s after another several years of concerted work to even get to the point of being able to do enough with human material to even get to safety testing. Its at least 15 years away in humans, I'd guess and maybe forever," said Greely.
Clearly, there are going to be people who think that this kind of research should not be permitted for numerous reasons including ethics and personal religious beliefs. But is there any genuine reason to be concerned, even if it does happen in humans?
"We meddle with nature constantly. Exhibit 1 - all of modern medicine. Exhibit 2 - the 8 million people born from IVF in the last 40 years who otherwise would never have existed," said Greely. All should be fascinated. Few should be scared - and those might want to review their feelings about IVF before making a conclusion about this possible new method," said Greely.