Mice with two fathers: novel idea but not applicable to humans

Texas reproductive scientist, Dr Richard R. Berhringer, has used induced pluripotent stem cell (iPS) technology to produce male and female mice that carry genes only from two fathers.

The technology has implications for agriculture and the preservation of endangered species - both cases where in certain circumstances it might be desirable to produce offspring without requiring female DNA.

However, Australian scientists have put dampeners on the notion suggested by the paper's authors that the technology might one day be used to produce offspring from two same-sex human fathers.

The process used is somewhat convoluted: the Behringer team first manipulated fibroblasts from a male (XY) mouse fetus to produce an induced pluripotent stem (iPS) cell line.

About one per cent of iPS cell colonies grown from this XY cell line spontaneously lost the Y chromosome, resulting in XO cells.

The XO iPS cells were injected into blastocysts from donor female mice. The treated blastocysts were transplanted into surrogate mothers, which gave birth to female XO/XX chimeras having one X chromosome from the original male mouse fibroblast.

The female chimeras, carrying oocytes derived from the XO cells, were then mated with normal male mice. Only some of the offspring were male and female mice that had genetic contributions from two fathers.

The technique could be usefully used for endangered species where no fertile females remain to produce both male and female offspring as long as there are multiple males still alive.

The researchers point out that the middle step in the process - the production of female XO/XX chimeras - might be obviated, meaning the technology could theoretically be used to produce two human offspring in a single generation, although a surrogate mother would still be required.

Several Australian researchers have hastened to comment that this is a very speculative observation from the paper authors, and there's little indication the technology could be adapted to humans any time soon, or even if it was, that it would be legal or ethical.

“The study is provocative in the way a good fictitious novel causes us to think about what defines our nature," said Dr Bryce Vissel, from the Garvan Institute of Medical Research.

"However as far as the practical translation of this work is concerned, there are significant barriers to its use in humans.

"The work answers interesting scientific questions about whether adult derived cells can be transformed to true stem cells.

"However in terms of making humans with two dads, the procedure is not viable. For now at least, the idea that we can have two fathers is a challenge to our thinking but not to reality.”

Dr Megan Munsie, Senior Manager, Research and Government, at the Australian Stem Cell Centre, concurs with Vissel.

“Whilst the findings in this paper are intriguing, whether such an approach could ever be applied to human reproduction is highly unlikely," she said.

"The mice were not born simply from two fathers. Rather they were created by a complex process dependent on access to fetal tissue, the creation of stem cells, additional embryos, surrogate mothers and natural mating.

"Leaving aside the practicalities of applying such a convoluted process to create a human baby, there are significant safety, ethical and legal considerations that prevent its application."

Currently it is prohibited in Australia to use technology that derives an embryo from the DNA from more than two individuals, says Professor Loane Skene of Law at the University of Melbourne and former Deputy Chair of the Lockhart Committee on human cloning and embryo research. Skene is concerned that media reports of this scientific finding could raise false hopes in same-sex couples of the possibility of producing biological offspring.

"The new research may lead same sex couples, both male and female, to hope that same sex couples may one day be able to have a child who is genetically related to both of them.

"However, even if such a technique was possible in humans, it could not lawfully occur in Australia under the current law."

According to Munsie, the benefits of iPS research doesn't necessarily lie in reproductive technologies.

"The real value of pluripotent stem cell research lies with increasing our understanding of normal development and disease,” she said.

The study was published today, Australian time, in the journal Biology of Reproduction.