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The mice with two Dads (and two Mums)…and countless other relatives that were used to produce them.

Across popular Sci Comms channels this week, you may have seen the story about the mice with two fathers who have gone on to have babies of their own.  

Previously, researchers have created mice with two mothers; however, attempts to do the same for mice with two fathers have been less successful. 

Making babies the old-fashioned way

As we all know, the conventional way of mammals making babies tends to work along the lines of a female producing an egg, and a male producing a sperm, which, after successful fertilisation, creates an embryo that has genetic material from both parents.  

Eggs and sperm contain only one copy of our chromosomes, and when they fuse together, the embryo ends up with two copies of the chromosomes, one from each parent. Doubling the amount of genetic material during reproduction means that one copy of each needs to be switched off, to prevent us ‘overdosing’ on the products of our genes, a process known as genomic imprinting.  

Genomic Imprinting and Epigenetics

Genomic imprinting does not change the sequence of our DNA. Instead, it chemically modifies the DNA which affects how our bodies “read” a DNA sequence, effectively turning genes “on” and “off”. Genomic imprinting is only one of the mechanisms through which the activity of our genes are controlled, and the study of how genes are ‘expressed’, without changing the DNA sequence, is known as epigenetics. 

Epigenetic changes are vital in biology. For example, as a single fertilised egg cell – the zygote– continues to divide, the resulting daughter cells change into all the different cell types in our bodies, including nerve cells, muscle cells, skin cells, blood cells, etc, by activating some genes while inhibiting the expression of others. 

Same sex biological parents

Recently, a team at Shanghai Jiao Tong University in China injected two mouse sperm cells into an empty mouse egg, before using epigenetic engineering- adding and removing methyl chemical markers – to reprogram the sperm DNA, to enable an embryo to develop. 

259 viable embryos were transferred to female mice, and just two offspring – both male – survived and grew to adulthood, so the success rate is very low. 

These two adult male mice both then fathered offspring the old-fashioned way, and their babies appeared normal in terms of size, weight and appearance. 

Using the lives of countless others

If we try and calculate the number of individual mice used to produce these 2 males with 2 Dads, the numbers are difficult to grasp. The sperm from 2 males was injected into an egg from a female mouse. That female mouse would have been injected with hormones to ‘super ovulate’, before she underwent surgery to harvest her eggs. How many mice were used for this step of the process? 

The engineered sperm cells and empty egg combo would then have been surgically implanted into another female mouse. Each embryo therefore had 2 Dads and 2 Mums. 

This was done 259 times. To produce only 2 offspring who survived to maturity. 

But why?

The reporting of this story has claimed that this has marked a significant breakthrough in the field, with the potential to impact many areas of science, from regenerative medicine and cloning to conservation. And for some reporters, this form of epigenetic engineering brings us “a step closer to two men being able to have genetic children of their own” 

Really? Genetic modification of human embryos is tightly restricted; for example, within the UK, we have the Human Fertilisation and Embryology Act 2008, which established the ‘14-day rule’. It limits the time a human embryo can be cultured in UK laboratories to a maximum of 14 days. Following a call from scientists to extend this limit to 28 days, the Nuffield Council on Bioethics is working with UKRI Sciencewise to run a large-scale dialogue to assess public opinions on reviewing the 14-day rule for human embryo research. 

Making a gene-edited baby is flat-out illegal in most of the world. But using epigenetic engineering in this way bypasses the need for genetic modification. In theory, epigenome editing could make the leap to our species under current legislation, but the emphasis here is firmly on the theoretical could. Whether it was technically possible is a different matter, as the state of the art of the technology is behind that of gene editing. 

‘Pinkwashing’ of animal experiments for basic research

I find it very troubling that much of the reporting of this risky, inefficient, and basic research using invasive procedures causing animals suffering, is offering some form of hope for same sex couples to have genetically related children of their own. Positioning this kind of science as “propelling us closer to enabling same-sex couples to have genetic children” is inappropriate and demonstrates a lack of understanding of the scientific, ethical and legal issues being touched upon. 

Sensationalist reporting gets headlines, reads, and clicks, I understand that. 

I also understand that people can have very strong feelings about having their own biologically related children.  

Let’s be honest

But we need to be honest about studies like this. This is a fundamental science project aimed at understanding more about genomic imprinting that was deliberately designed to create headlines and publicity.  

But the dissemination of its output in this way gives false hope, and that is not right. 

We need to hear more voices like Christophe Galichet of the Sainsbury Wellcome Centre “While this research on generating offspring from same-sex parents is promising, it is unthinkable to translate it to humans due to the large number of eggs required, the high number of surrogate women needed, and the low success rate,” as he told New Scientist. These voices need to be at the forefront of reporting so that the sensationalist claims of publicists can be appropriately positioned and tempered. 

And spare a thought for the poor mice – all of the hundreds, if not thousands. All of them are individuals with their own feelings, interests and needs, but all of them are used by humans to try and understand basic elements of biology, and the mechanisms through which we (and they) came to be. 

The original study is published in PNAS. 

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