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Imagine you鈥檙e having trouble conceiving only to be told you can鈥檛 father children of your own because you don鈥檛 produce viable sperm. If your partner is to get pregnant, it will have to be with donor sperm.
In most cases like this, the cause isn鈥檛 clear. But sometimes it is due to specific genetic mutations 鈥� and in these instances a radical treatment could soon be available.
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The idea is to extract the stem cells that give rise to sperm and correct the mutation. The corrected stem cells would then be implanted back into the man鈥檚 testes, allowing him to produce healthy sperm and father his own biological child.
The hope is that men will produce enough sperm to conceive naturally, sparing them and their partners from the physically and psychologically demanding process of IVF. And their children will be just the same as yours or mine; they will just have the normal version of the gene that was faulty in the father.
All this can already be done in mice, and several groups are working on it for humans. It is much more difficult in people, however, because human sperm stem cells are very hard to grow outside the body, says Geert Hamer of the University of Amsterdam, who studies these cells. But it could become possible within the next five or 10 years.
Ethical red line
Curing infertility would mean a huge amount to many couples. But there鈥檚 a bigger story here. When I read a recent review of the field by Hamer, what struck me was that this was the first good reason I鈥檝e come across for starting to edit the genomes of our children.
Since the CRISPR genome editing method burst onto the scene a couple of years ago, reams have been written about how it could be used to alter our genes and cure disease. Few argue with its use to help treat blindness or cancer. But using it to prevent genetic diseases is far more controversial because it would involve changing the DNA of our children 鈥� it would be 鈥済ermline鈥� gene editing, editing of sperm, eggs or embryos. For many, this seemingly noble goal is an ethical red line.
It鈥檚 a discussion that has seen much hand-wringing, but what鈥檚 often been missing from the debate is the fact that we don鈥檛 need to resort to germline gene editing to prevent inherited diseases caused by single mutations. This can already be done more safely with existing screening methods such as of IVF embryos.
The other reason for germline genome editing is to make designer babies. Whatever you think of this, the practical issue is that we don鈥檛 (yet) know how to turn our children into Einsteins.
But allowing previously infertile men to father a biological child of their own does seem like a persuasive reason to allow genome editing. What鈥檚 more, this approach will overcome the key safety issues revealed by the first such attempts.
Modified sperm
In these experiments, unviable embryos rather than sperm were edited. The result was a mixture of modified and unmodified cells, which would be unacceptable if, say, you wanted to use genome editing to stop people inheriting harmful mutations. If the desired genetic edit is made much earlier, so it is present in every sperm, every cell in the embryo will have it. What鈥檚 more, the corrected sperm stem cells could be checked before re-implantation to ensure there are no undesired changes 鈥� the other big concern.
Modifying sperm has been suggested before to get around the safety issues, and doing this to cure infertility is something that many people strongly desire 鈥� and would pay handsomely for. It seems certain that IVF clinics in some parts of the world will start offering this service as soon as it becomes technically possible. So treating male infertility may be the thing that prompts us to cross that red line and usher in the germline genome editing revolution.
And if it proves safe 鈥� and acceptable 鈥� then undoubtedly genome editing will start to be used for other purposes, too. After all, if you are correcting one mutation, why not correct a few other harmful mutations while you are at it.
We are all born with hundreds of mutations 鈥� too many to screen out using PGD 鈥� that increase our risk of diseases like cancer and Alzheimer鈥檚 in later life. Most have only a tiny effect but if we could correct 100 of them in one go 鈥� which could well be doable with CRISPR 鈥� it could make a massive difference to an individual鈥檚 health.
Some will call this a slippery slope. For others, it鈥檚 about looking after the health of our grandchildren and great grandchildren. But whether this prospect appals or enthrals you, I鈥檓 betting that curing male infertility will be what gets us there.
Journal reference: Human Reproduction Update, DOI: 10.1093/humupd/dmw017
