5Things2KnowAboutIvG
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Five things to know about IVG – a new way to have babies by turning any cell in our bodies into sperm or egg cells
Already trialled in mice, IVG or in vitro gametogenesis is the next frontier in reproductive medicine, allowing infertile people, same-sex couples, groups of more than two, or individuals, to become parents

Sperm from a man’s testes and an egg from a woman’s ovaries must come together for fertilisation to eventually produce offspring – it’s basic biology, isn’t it? Well, perhaps not in the future. A new experimental lab technology rapidly advancing in mouse studies suggests that some day, embryos could be created by reprogramming any type of adult cell to become a sperm or egg cell.

Known as in vitro gametogenesis (IVG), the technique would allow not only the medically infertile to have wholly biological children – that is, not involving any donors – but also same-sex couples, groups of more than two people, and even a single individual. IVG could also make prenatal selection a much more refined and comprehensive process than it is today, allowing for the selection of embryos that result in “perfect” children.

In a newly published commentary in the journal Science Translational Medicine, a trio of scholars from Harvard and Brown universities in the US argue that while IVG could unravel the fundamental mechanisms of genetic forms of infertility and pave the way to a range of new therapies, it also raises a number of vexing legal and ethical questions that society should address before IVG becomes ready for mainstream clinical use in human patients.

Internal view of a human fetus at approximately 10 weeks.
Existing assisted-reproduction technologies such as in vitro fertilisation (IVF) and mitochondrial replacement therapy still require gametes – the sperm and the egg – that come from a man and a woman. But that’s not the case for IVG.

“There’s something troubling about an inexhaustible supply of gametes that can be fertilised into an inexhaustible supply of embryos,” says co-author Eli Adashi, professor of medical science at Brown.

Co-author Glenn Cohen, professor at Harvard Law School, adds: “IVG has the potential to upend one of the most traditional elements of human culture – our understanding of what parenthood is and how it occurs. It is critical for law and medical ethics to grapple with the far-ranging implications of this new technology.”

Law and medical ethics will need to grapple with the far-ranging implications of this new technology.
Wondering about what the future holds? Here are five things you should know about IVG.

1. Basic research on IVG is occurring across the globe.

In a commentary in the Journal of Law and the Biosciences published in July 2016, June Carbone, the Robina Chair in Law, Science and Technology at the University of Minnesota in the United States, offers examples: in September 2015, a French biotech start-up, acting together with the French National Centre for Scientific Research, announced that it had produced human sperm outside the body.

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In 2014, researchers at Cambridge University in the UK and the Weitzmann Institute in Israel reported that they had created human egg and sperm cells in the lab, by coaxing adult stem cells to produce early-stage egg and sperm cells. And OvaScience, a publicly traded Boston company, is exploring the use of egg precursor cells, which exist in a woman’s ovaries, to produce new ova.

“These developments offer the potential for creating potentially unlimited new gametes,” says Carbone.

2. IVG holds enormous potential as a treatment not only for infertility but also for myriad currently untreatable diseases.

The Harvard and Brown scholars say the technique may provide an inexhaustible supply of lab-made embryonic stem cells for research and therapeutic use as a tantalising alternative to scarce human embryonic stem cells, which are currently in limited supply due to ethical considerations and regulatory restrictions.

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By creating differentiated cells and tissue lines with different genetic mutations, researchers can better understand the cellular and molecular aberrations responsible for DNA defects that cause a range of genetic disease, and test potential drug therapies.

3. IVG is likely to influence understandings of what it means to be a family.

With “multiplex” parenting, where groups of more than two individuals (whether all male, all female, or a combination) procreate together, producing children who are the genetic progeny of them all, the intended parents would not have the type of genetic relationship we associate with parent and child in “normal” reproduction, says Sonia Suter, a law professor at George Washington University, in an article in the Journal of Law and the Biosciences in 2016.

As the number of individuals involved increases, the genetic distance from the child to any one intended parent would increase: from 25 per cent genetic connection with quadruples to 12.5 per cent with octuples, and so on. Suter says: “The resulting children would therefore be ‘orphaned’, since their genetic ‘parents’, the embryos, would have died before the child was even born.”

And with solo IVG, where single individuals may be able to procreate without the genetic contribution of another individual, the child would share virtually 100 per cent of its genome with its parent. Would that make the child a clone?

The Harvard and Brown scholars say the technique may provide an endless supply of lab-made embryonic stem cells.
4. People could be made parents without their knowledge or consent.

Since human embryos could be derived from easily harvested sources such as hair and skin cells, IVG is not only ethically troubling but also raises worrisome legal questions cutting to the very core of the legal definition of parenthood, the Brown and Harvard scholars say.

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5. The safety for the future children is a concern.

There is still limited knowledge about the risks associated with IVG. Suter says: “For example, we have minimal knowledge about the implications of switching cell types from differentiated to undifferentiated states and the implications of erasing and resetting imprinting patterns to facilitate reproduction... Because IVG might potentially affect the resulting children’s germ lines, uncertainty also exists with respect to the potential risks to future generations.”
 

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