New three-parent embryo research leaves many questions unanswered

A new IVF-based technique ‘is likely to lead to normal pregnancies and reduce the risk that babies born will have mitochondrial disease’, according to researchers at the Wellcome Trust Centre for Mitochondrial Disease at Newcastle University.

Published today (Wednesday 8 June 2016) in the journal Nature, scientists report the first in-depth analysis of human embryos created using a new ‘three-parent’ technique devised to reduce the risk of mothers passing on mitochondrial disease to their children.

Mitochondrial diseases are inherited maternally and cause a variety of severe conditions that currently have no cure. The UK government has recently legalised the controversial use of embryos carrying DNA from three genetic parents to prevent their transmission, but the proposed techniques have been criticised on both ethical and safety grounds (see my previous review).

One of these techniques, called ‘early pronuclear transfer’ (see picture), involves transplanting the nucleus from a fertilised egg into a donated egg, which contains healthy mitochondria, shortly after fertilisation.

Today researchers, in a study involving over 500 eggs from 64 donor women, published results which they say show that the new procedure does not adversely affect human development and will greatly reduce the level of faulty mitochondria in the embryo. They further claim their results suggest that the technique will lead to normal pregnancies whilst also reducing the risk of babies having mitochondrial disease.

The results of the new study will be considered by the Human Fertilisation and Embryology Authority‘s (HFEA) Expert Scientific Panel. The HFEA will ultimately decide whether to issue the first licence to a clinic. A licensed clinic would allow couples affected by mitochondrial disease to have the choice of whether to use pronuclear transfer to try and have healthy children.

What should we make of it all?

This new research might have calmed the nerves of already committed enthusiasts for this controversial technique but it leaves many questions still unanswered.

The Newcastle researchers admit in their press release that one of five stem cell lines derived from embryos they created showed an increase, rather than a decrease, in the percentage of mitochondrial DNA carryover (this important fact is left out in Fergus Walsh's misleading BBC report). 

Rather than bringing reassurance this actually confirms concerns highlighted just one month ago by another researcher in the same journal Nature that three-person embryos ‘may fail to vanquish mutant mitochondria’.

Scientists in New York showed that ‘even if a small number of mutant mitochondria are retained after the transfer’ – an admittedly common occurrence — they can ‘outcompete healthy mitochondria in a child’s cells and potentially cause the disease the therapy was designed to avoid’.

Early embryos that ‘look’ normal (they were only grown to six days) do not necessarily translate into older embryos, fetuses, babies and children that are normal. The deep concerns that this technique will not work, or will work partially producing a whole host of new problems, have not yet been addressed.

It is noteworthy that this other US research has not been given attention by the Newcastle team and the BBC. Not as convenient perhaps?

Serious ethical and safety concerns remain, including the risky and invasive harvesting of large numbers of human eggs from donor women and the identity confusion of genealogically confused progeny, if we ever get that far.  

Adoption of children, babies or embryos still remains a viable and safe alternative for these families and DNA editing, which has already been successfully used to prevent transmission of mitochondrial disease in mice, is a far more precise, specific, clever, natural and ethical solution to this problem than stripping nuclei out of embryos and transplanting them into donor eggs.

The end does not justify the means and the greatest scientific advances are always ethical. The human embryo must always be treated with the utmost respect. 

It is noteworthy that Shimya Yamanaka, the 2012 Nobel prize winner,  through patient and meticulous research, discovered an ethical alternative to embryo research that revolutionised scientific thinking and won him a Nobel prize.

By contrast, this new research is unnecessary, unethical and still unproven to work in non-human primates, let alone human beings. We should put a halt to it and instead pursue scientific solutions that are more safe, natural, ethical and scientifically precise – more Michelangelo than Picasso.

This is a boundary that should not have been crossed. There are other options (see my blogpost on ‘thirteen solutions to mitochondrial disease assessed’) which offer better solutions. 

Thirteen ‘solutions’ to mitochondrial disease assessed

Mitochondrial disorders are passed on through a mother’s mitochondrial DNA. They are progressive and can be very disabling but are thankfully relatively rare. They can cause stillbirth, death in babies and children, or may onset with severe effects in adulthood, such as blindness or heart failure.

As there is currently no treatment for most of them the majority of ‘solutions’ are aimed at prevention.

1. Hitler’s solution would have been euthanasia. His chief physician, Karl Brandt, believed that killing disabled people not only relieved the burden their lives imposed on the state, but also released them from lives that were not worth living: 'My underlying motive was the desire to help individuals who could not help themselves...such considerations should not be regarded as inhuman.’

2. Infanticide would be the answer of Watson and Crick, the scientists who discovered the molecular structure of DNA. Along with eugenicist Margaret Sanger and bioethicist Michael Tooley they advocated killing disabled neonates on the grounds that they were not fully human. Dutch doctors do the same today under the Groningen Protocol.

3. Prenatal diagnosis and abortion is the choice of most British mothers carrying a disabled baby. The fetal DNA can be examined through chorionic villus biopsy or amniocentesis followed by induced intrauterine death. 91% of babies with Down’s syndrome detected prenatally have their lives ended this way. Whether you see killing a new-born baby in a hospital ward as any different from killing in the womb a few weeks earlier will depend on your view of the unborn child.

4. Pre-implantation genetic diagnosis (PGD) is favoured by those who believe that killing a human embryo is different from killing a fetus. Produce embryos by IVF, examine them in the laboratory, and discard or destroy those which are affected. Then implant only those without a disability.

5. Mitochondrial transplantation (ie. three parent embryo technique) was recently approved by the British parliament. Take an egg with faulty mitochondria before or after fertilisation, shell out the nucleus and then transplant it into a donor egg from which the nucleus has been removed. This is currently untested and may result in worse genetic defects than those one is trying to prevent. But then prenatal diagnosis and abortion can be used as a back-up.

6. Use IVF with an egg from an unaffected donor. The baby would not carry mitochondrial disease as it can only be picked up from the affected mother. But the baby would also not be biologically related to its mother. Also it introduces a third person into the marriage and family tree and in an unnatural way.     

7. DNA editing has been successfully employed in mice. Produce an embryo by IVF. Inject the embryo with a segment of RNA designed to produce DNA-cutting enzymes. Snip out the faulty gene and implant the embryo in its mother’s uterus. Grow to term. An elegant form of molecular microsurgery not yet tested in humans but which runs the risk of passing any introduced genetic errors down the generations. Not yet legal in Britain.

8. Contraception. An affected couple who didn’t feel comfortable with approaches 1-6 above might just choose not to have children and use contraception on every occasion.

9. If they wanted to be absolutely sure (as no method of contraception is 100% foolproof) they might opt for abstinence.

10. Alternatively a woman known to be a carrier of mitochondrial disease might choose to remain single.  

11. Another option might be to adopt a frozen embryo related to neither parent in order both to carry a child to term and to give it chance of life it might not otherwise have. There are over 600,000 embryos in the US alone for which embryo adoption is a possibility.

12. Then there is the possibility of baby or child adoption. This provides an affected couple with a child and a child with a home.

13. Finally, they may opt simply to go ahead and accept the child they are given, whether it has mitochondrial disease or not, and regardless of how badly it is affected. After all, isn’t every human being precious and worthy of the greatest protection, care, respect and the best treatment that is available.

So which of these thirteen options is the best? The answer to that question will depend on one’s fundamental world view including one’s view of the status of the human embryo and fetus and one’s view of the marriage bond.

Most, but by no means all, would be repulsed by options 1 and 2 – euthanasia and infanticide.

Those who do not see the fetus as a human being with rights would opt for 3 – prenatal screening and abortion. 

If they are squeamish about abortion but happy with embryo disposal they might opt for option 4 – pre-implantation genetic diagnosis (PGD).

If they are desperate to have a child genetically related to both parents they might risk 5 – the three parent embryo - or 7 – DNA editing. On the other hand if they are happy for the baby to be related just to the father they might opt for 6 – IVF with an egg donor.

Those who cannot contemplate 1-6 for whatever reasons have three options: choosing not to conceive either through contraception, abstinence or remaining single; adopting an embryo, baby or child; or going ahead and having the baby anyway.

What do I think myself?

For me three crucial ethical principles come to bear.

The first is the status of the human embryo. As I have previously argued I see the human embryo as a living person worthy of the utmost respect, empathy, protection and wonder. So that rules out options 1 to 4. The end of having an unaffected baby does not justify the means of taking human life, at any stage.

Second is the inviolability of the marriage bond (dealt with in more detail here). To me introducing a third person into the marriage bond violates the biblical principle of one man, one woman, for life. Although the lust and cheating elements of adultery may not be present, the use of donor gametes still constitutes a form of biological adultery. So option 6 is out. 

Third I don’t have an absolute objection to IVF per se (provided that the couple is married, all embryos are re-implanted and that there are no donor gametes) but I do think that the creator designed human reproduction to occur as a result of the union of egg and sperm. So, even apart from concerns about safety and germ-line manipulation, the act of cobbling together a human being using organelles from three different individuals (the three parent embryo) not only introduces a third person into the marriage bond but disrupts the divinely designed reproductive process. This, for me, rules out option 5.

Of the remainder DNA editing (7) is most interesting. I do not have an a priori objection to germ-line gene therapy but I do have serious concerns about its safety. Its attractiveness is that, unlike the three parent embryo solution, it offers the possibility of restoring a whole embryo to health. But it could only be considered if was shown to be absolutely safe and effective in non-human primate studies and this has not thus far been done.

So I am left with options 8-13. 8-10 are feasible but rule out parenthood unless accompanied by adoption. Embryo adoption (11) makes parenthood possible and saves a life. But only if that embryo is already in existence and would otherwise perish. I do not believe that it is right to create embryos that are not going to be implanted and I do not support surrogacy (which is what this essentially is) other than to save an existing embryo. Baby or child adoption (12) may not save a life but it does potentially give a child in care or in fostering a loving home.

Having a baby regardless knowing that it could be affected (13) will require a great degree of both courage and love, and is perhaps the costliest solution of all.

God shows his compassion toward us through loving care given at great personal cost. He adopts us into his family. He loves us in spite of the fact that we are disabled by sin. He seeks to bring us back into a loving relationship with himself. So for me, options 11-13 most closely resonate with the heart of God himself. 

New DNA editing technique for mitochondrial disease may render three parent embryos redundant

A new technique for removing harmful genes from strands of DNA could potentially obviate the need for three-parent embryos for preventing mitochondrial disease.

Researchers from the Salk Institute for Biological Studies in La Jolla, California, have reported success for the first time in using gene-editing technology to prevent mitochondrial diseases being passed from female mice to their offspring.

Mitochondrial diseases are inherited maternally and cause a variety of severe conditions that currently have no cure. The UK government has recently legalised the controversial use of embryos carrying DNA from three genetic parents to prevent their transmission, but the proposed techniques have been criticised on both ethical and safety grounds (see my previous review).

This new research, published in the 23 April edition of Cell magazine, involves injecting affected embryos with RNA which leads to the production of enzymes which specifically target and remove faulty genes.

It is reported on this week in Nature, Popular Science, Medical News Today, Tech Times, and (amazingly) has even come to the attention of the BBC. Ted Morrow's blog gives a useful overview.

Authors Alejandro Ocampo and Juan Carlos Izpisua Belmonte realised that reducing the amount of mutant mitochondrial DNA in an egg or fertilised embryo could reduce the chance of mitochondrial disease developing.

They achieved this by injecting mouse embryos with a segment of RNA designed to produce DNA-cutting enzymes called restriction endonucleases and transcription activator-like effector nucleases (TALENs).

These enzymes then sought out mitochondria with mutated DNA and removed it while leaving the normal mitochondrial DNA intact.

The treated embryos were then transferred to female mice where they developed normally and resulted in healthy pups with low levels of the targeted mitochondrial DNA.

These pups later went on to give birth to healthy offspring themselves, demonstrating that this is a viable approach for preventing transgenerational transmission of mitochondrial diseases.

The researchers then trialled the TALENs using mouse eggs that contained genetic material from human patients mitochondrial DNA mutations known to cause two disorders - Leber's hereditary optic neuropathy and dystonia (LHOND) and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP).

Again, the technique resulted in a significant reduction of the mutated DNA.

It is early days with this new technique which will need thorough testing in mice and non-human primates before being ready for testing in humans.

However it has several obvious advantages over controversial three parent embryo techniques.

First, it does not require DNA donation and so avoids the health risks to donors (such as OHSS) associated with egg harvesting.

Second, it does not involve cell nuclear replacement (cloning) technology with all its safety concerns.

Third, it can be tested on eggs as well as embryos and does not involve the destruction of existing embryos.

Fourth, it is technically much easier to perform than the mitochondrial (or more accurately cytoplasmic) replacement used in three parent techniques. RNA injection is a technique that can be carried out relatively easily in IVF clinics.

Fifth, it appears to be a far more finely targeted technique, eliminating faulty genes rather than replacing the whole cytoplasm with all of it mitochondrial and other organelles. More like a sniper than a blunderbuss or carpet bomber.

Finally it does not produce offspring with three genetic parents.

However, we are still left with three concerns.

First, this new technique does still involve genetic medication of the germline, and the possibility that any ‘mistakes’ in editing would be passed on down the generations. This has already led David King of Human Genetics Alert to reject it outright.

Second, we cannot be sure, without a lot of further research, just how finely tuned it is as an editing tool. How much damage might be done to other genes in the vicinity and what effect might this have? 

Third, once this tool is more widely available, might it then be used by unscrupulous researchers or scientists to edit DNA in more dangerous contexts?

However, were it to work as well as some are hoping, it could potentially reduce the three parent technique, over which so much time, money and sweat has been expended, to a tiny historical footnote.

It will be intriguing to see how this research progresses and how long it takes for those British science journalists and parliamentarians who have been pushing three parent embryos so aggressively to take notice. 

Three-parent embryos for mitochondrial disease – the five big questions MPs failed to answer

Today MPs in the House of Commons voted 382-128 to make Britain the first country in the world to offer controversial ‘three-parent’ fertility treatments to families who want to avoid passing on mitochondrial diseases to their children. 

Last week forty scientists from 14 countries urged the British legislature to approve the new laws allowing mitochondrial DNA transfer.

The stance of scientists created huge pressure for MPs who risked being labelled ‘ignorant’ or uncaring for objecting. But the question is not nearly as simple as it looks on first appearance. These new regulations are dangerous. No other country has officially legalised the techniques and no one can predict what the consequences for future children will be.

The Department of Health claimed widespread public support for the measure – despite its own consultation showing a majority (62%) actually oppose the plans. In addition a ComRes poll conducted in August 2014 found that only 18% of people support a change in the law to permit the creation of three-parent children through genetic modification.

There are about 50 known mitochondrial diseases (MCDs), which are passed on in genes coded by mitochondrial (as opposed to nuclear) DNA. They range hugely in severity, but for most there is presently no cure and little other than supportive treatment (see CMF briefing paper here and previous articles on the issue here).

It is therefore understandable that scientists and affected families want research into these two related ‘three-parent embryo’ techniques (pronuclear transfer (PNT) and maternal spindle transfer (MST)), to go ahead. But there are good reasons for caution.

Here are the five big questions MPs failed to answer today.

Is it necessary?

This is not about finding a cure. It is about preventing people with MCD being born. We need first to be clear that these new technologies, even if they are eventually shown to work, will do nothing for the thousands of people already suffering from mitochondrial disease or for those who will be born with it in the future. Parents will generally not even know that they run a risk of producing an affected baby until after the birth of the first. And it is very difficult to predict the severity of the disease in a given case. There is huge variation even within affected families.

Mitochondrial disorders are also relatively rare. Perhaps 1 in 200 children are born each year with abnormal mtDNA but only 1 in 10,000 are severely affected. It was suggested in 2001 that the proposed techniques, if they work, could 'save' around ten lives each year. 

Last week however a JME article upped these numbers to 150.  I'm not in a position to seriously dispute these figures as I don't have access to the patient data on which they are based.  

Nevertheless, to jump from 10 to 150 (via 20 and 80) is quite a jump and raises serious questions about creative accounting.  How were their original estimates so off the mark, if the new estimates are supposedly more reliable?  Moreover, there is a fair bit of extrapolation involved and the validity of this depends on the distribution of people with mutant mitochondrial DNA being evenly spread throughout the UK and also the USA.

Either way we are not talking about huge numbers here. There are also already some alternative solutions available for affected couples including adoption and IVF with egg donation.

Is it safe?

This is far from established. Each technique involves experimental reproductive cloning techniques (cell nuclear transfer) and germline genetic engineering, both highly controversial and potentially very dangerous. Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California has argued  in an piece titled ‘A slippery slope to germline modification’ that were the United Kingdom to grant a regulatory go-ahead, it would unilaterally cross ‘a legal and ethical line’ observed by the entire international community that ‘genetic-engineering tools’ should not be used ‘to modify gametes or early embryos and so manipulate the characteristics of future children’.

Cloning by nuclear transfer has so far proved ineffective in humans and unsafe in other mammals with a large number of cloned individuals spontaneously aborting and many others suffering from physical abnormalities or limited lifespans. Also, any changes, or unpredicted genetic problems (mutations) will be passed to future generations. In general, the more manipulation needed, the higher the severity and frequency of problems in resulting embryos and fetuses.

Prof Stuart Newman's recent article in Huffington Post is a brilliant analysis of the way scientists have pulled the wool in misrepresenting the scientific facts to a gullible public and parliament (See also  Marcy Darnovsky's excellent open letter to MPs on safety issues).

Will it work?

There are reasons to be deeply sceptical about the grandiose claims being made by scientists and patient interest groups with vested interests. This technology uses similar ‘nuclear transfer’ techniques to those used in ‘therapeutic cloning’ for embryonic stem cells (which has thus far failed to deliver) and animal-human cytoplasmic hybrids (‘cybrids’). The wild claims made about the therapeutic properties of ‘cybrids’ by the biotechnology industry, research scientists, patient interest groups and science journalists duped parliament into legalising and licensing animal human hybrid research in 2008.

Few now will remember Prime Minister Gordon Brown’s empty promises in the Guardian on 18 May that year of ‘cybrids’ offering 'a profound opportunity to save and transform millions of lives' and his commitment to this research as 'an inherently moral endeavour that can save and improve the lives of thousands and over time millions of people'. That measure was supported in a heavily whipped vote as part of the Human Fertilisation and Embryology Bill, now the HFE Act. But ‘cybrids’ are now a farcical footnote in history. They have not worked and investors have voted with their feet. Ironically, it was in that same Act of Parliament, that provision for this new research was also made.

In In early 2009 it was said that there was no funding for cybrids in the UK and ironically only three research licences were granted: to Dr S Minger of King’s College London (R0180), to Prof Lyle Armstrong of University of Newcastle Upon Tyne (R179) and to Dr Justin St. John of the University of Warwick (R183).

What happened? Basically zilch! Dr St John emigrated to Australia (where such work is prohibited), Lyle Armstrong eventually switched to working with iPS cells (a more fruitful ethical alternative) and Stephen Minger left academia to work for GE Healthcare (where he promotes work with hES cells for drug screening but definitely does not work with interspecies combinations). 

This is hugely relevant for the three-parent embryo debate as 223 charities, egged on by the false promises of the scientific community, wrote to the Prime Minister in 2008 to get him to reverse his decision on hybrids and not stand in the way of disease treatments. Déjà vu?

Is it ethical?

No, there are actually huge ethical issues. A large number of human eggs will be needed for the research, involving ‘harvesting’ that is both risky and invasive for women donors. How many debt-laden students or desperate infertile women will be exploited and incentivised by being offered money or free IVF treatment in return for their eggs?

Egg donation is neither straightforward nor harmless. It involves using drugs to shut down the woman’s own ovaries, then stimulating them to produce multiple follicles then surgically extracting the resulting eggs. This all has significant health and ethical implications for the donor, including health risk to the donor from powerful hormonal treatments, injections, invasive surgery, and yet it is not for her own benefit.

A study at the Newcastle Fertility Centre, reported in Human Fertility, found that more than 20 eggs were collected from at least one in seven patients, that 14.5% of these women were subsequently admitted to hospital and nearly all reported symptoms consistent with ovarian hyperstimulation syndrome (OHSS). We do know from a recent report that just under half of 864 reported clinical incidents between 2010-2012 were due to OHSS. And: ‘Each year approximately 60 instances of severe OHSS and 150 cases of moderate OHSS are reported to the HFEA.’

How many thousands of human embryos will be destroyed? If it ever works, what issues of identity confusion will arise in children with effectively three biological parents? What does preventing those with mitochondrial disease being born say about how we value people already living with the condition? Where will this selection end? Some mitochondrial diseases are much less serious than others. Once we have judged some affected babies not worthy of being conceived, where do we draw the line, and who should draw it?

Is the debate being handled responsibly?

No. The research scientists involved have huge financial, ideological and research-based vested interests and getting the regulatory changes and research grants to continue and extend their work is dependent on them being able to sell their case to funders, the public and decision-makers. Hence their desire for attention-grabbing media headlines and heart rending (but highly extreme and unusual) human interest stories that are often selective about what facts they present.

It must be tempting for politicians to make promises of ‘miracle cures’ in years to come which no one may remember. But I suspect it is much more about media hype than real hope.

This new push is being driven as much by prestige for government, research grants for scientists and profits for biotechnology company shareholders as anything else.

Cool heads required

MPs know there is widespread public opposition to growing genetically modified (GM) crops in the UK. How much more cautious should they be about allowing GM babies to be created?

These techniques are highly experimental, unproven, known to be very unsafe (bear in mind that children’s lives will be the experiment), ineffective, costly, a waste of public money, insufficiently understood, unnecessary (only potentially helping between 10 and 150 families a year) and will require large numbers of eggs to proceed, even for just a few families.

Genuine concerns about this new mitochondrial technology have been swept aside in Britain in the headlong rush to push the scientific boundaries.

Furthermore in many countries around and the world, and by commentators from both secular and faith based scientific backgrounds, Britain is viewed as a rogue state in this area of research.

This move is both premature and ill-conceived.

Fiona Bruce MP  laid a motion opposing the approval of the regulations which cuts to the chase and encapsulates the concerns beautifully. But sadly it was rejected.

“That this House declines to approve the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015 because many of the safety tests recommended by the Human Fertilisation and Embryology Authority Expert Panel have yet to be performed and peer-reviewed and their results made public; because no other country in the world has legalised the proposed techniques for ethical reasons; because major international bodies including the United States Food and Drug Administration have expressed the view that not enough preclinical work has been done to ensure that the proposals are safe; because they permit the genetic modification of human embryos and oocytes; because these regulations permit human embryos to be created only to be destroyed; because there are unanswered questions regarding the legality of the regulations at both domestic and international level; and because this House should not be asked to approve regulations of such ethical significance without a fully informed debate and before the results of the above safety tests are available for consideration.”

MPs should have kept cool heads and instead concentrated on finding real treatments and providing better support for affected individuals and their families rather than spending limited health resources on unethical, risky and highly uncertain high tech solutions that will most likely never deliver.

I hope the Lords will subject this issue to more careful scrutiny when they consider it in a few weeks' time.

Scientists dismiss opposition to three-parent embryos as 'ignorant' - haven’t we been here before?

Next Tuesday MPs in the House of Commons will be asked to vote to make Britain the first country in the world to offer controversial ‘three-parent’ fertility treatments to families who want to avoid passing on mitochondrial diseases to their children.

This is final crunch time so it’s not surprising that the media is giving the debate high profile.

Earlier this week forty scientists from 14 countries urged the British legislature to approve the new laws allowing mitochondrial DNA transfer.

Yesterday the Anglican and Catholic Churches struck back criticising the move on grounds of ethics, efficacy and safety.

Today the scientists have done their usual retreat at such moments and accused the churches of ‘ignorance’: ‘The objections are all religious, they just don’t understand the science’.

But it’s precisely because the scientists have not effectively made their case that Christians with science backgrounds are raising objections.

Over the last three years Christian Medical Fellowship – an organisation with over 4,500 British doctors as members – has published over 20 articles (see here and here) raising serious questions not just about the ethics, but also about whether these techniques are safe, workable or even necessary.

We have also warned repeatedly about the dangers of these techniques crossing two scientific rubicons in allowing both germline alteration (generationally transmissible genetic modification) and also cell nuclear replacement.

These warnings have gone unheeded. 

Most of the MPs who will be voting on Tuesday do not have scientific backgrounds and are not experts in ethics – and will be basing their votes on what they are being told by the scientific community.

There are about 50 known mitochondrial diseases (MCDs), which are passed on in genes coded by mitochondrial (as opposed to nuclear) DNA. They range hugely in severity, but for most there is presently no cure and little other than supportive treatment.

It is therefore understandable that scientists and affected families want research into these two related ‘three-parent embryo’ techniques (pronuclear transfer and maternal spindle transfer) to go ahead.

But there are very good reasons for caution.

This is not about finding a cure. It is about preventing people with MCD being born. We need first to be clear that these new technologies, even if they are eventually shown to work, will do nothing for the thousands of people already suffering from mitochondrial disease or for those who will be born with it in the future.

Furthermore four big questions remain: Is it safe? This is far from established. Will it work? We remain deeply sceptical. Is it ethical? There are huge ethical questions. Is it even necessary? There are actually already alternative solutions available for affected couples including adoption and IVF egg donation.

These technologies use similar ‘nuclear transfer’ techniques to those used in ‘therapeutic cloning’ for embryonic stem cells (which has thus far failed to deliver) and animal-human cytoplasmic hybrids (‘cybrids’).

The wild claims made about the therapeutic properties of ‘cybrids’ by the biotechnology industry, research scientists, patient interest groups and science journalists back in 2008 duped parliament into legalising and licensing animal human hybrid research.

Few now will remember Gordon Brown’s empty promises in the Guardian on 18 May that year of ‘cybrids’ offering 'a profound opportunity to save and transform millions of lives' and his commitment to this research as 'an inherently moral endeavour that can save and improve the lives of thousands and over time millions of people'.

That measure was supported in a heavily whipped vote as part of the Human Fertilisation and Embryology Bill, now the HFE Act. But ‘cybrids’, as we predicted at the time, are now a farcical footnote in history.

They have not worked and investors have voted with their feet. Ironically, it was in that same Act of Parliament, that provision for this new research was also made.

And yet it was the same scientists using much the same arguments who were pushing it through then. Such a track record does not engender trust in their judgments, especially when one considers the deep ideological and financial vested interests involved. 

I have a profound sense of déjà vu here. History will of course prove who is right. 

But don’t say we didn’t warn you.

New government consultation on three parent embryos asks the wrong questions

The Department of Health today has published for consultation draft regulations to allow mitochondrial donation to prevent the transmission of serious mitochondrial disease from mother to child.

The consultation will close on 21 May.

This new government consultation is not asking whether but how these controversial techniques for mitochondrial disease should be implemented. In so doing it sweeps aside genuine ethical and safety concerns in the headlong rush to push the scientific boundaries. 

Rather like the motorist who asked an Irishman for directions and received the answer, ‘I wouldn’t start from here’ the government in this new consultation is actually asking the wrong questions.

Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California has previously argued in an piece titled ‘A slippery slope to germline modification’ that were the United Kingdom to grant a regulatory go-ahead, it would unilaterally cross ‘a legal and ethical line’ observed by the entire international community that ‘genetic-engineering tools’ should not be used ‘to modify gametes or early embryos and so manipulate the characteristics of future children’. This is now happening.

She is not alone in her concerns. Just this week advisors to the US Federal Food and Drug Administration (FDA) have expressed concern that the three-parent embryo procedure could lead to human gene manipulation and have questioned its ethics and whether the research into it is as far advanced as some of its advocates claim.

In short, should we be giving treatments to human beings that have not yet been tested fully in animals?

It is deeply regrettable that the government intends to press on recklessly with this controversial technology in real patients in the face of genuine concerns about safety, effectiveness and ethics which have so far prevented its implementation anywhere else in the world.

In many countries around and the world, and by commentators from both secular and faith based scientific backgrounds, Britain is viewed as a rogue state in this area of research.

The Government gave an assurance in 2009 that regulations to allow treatment would not be made until any proposed techniques were considered to be effective and safe for use in treatment.

It has still to deliver on this undertaking. 

Further background

Christian Medical Fellowship has recently published a paper on ‘three parent embryos for mitochondrial disease’ which was strongly critical of this new technology on both theological and scientific grounds.

This followed submissions that we made on the issue to both the Human Fertilisation and Embryology Authority (HFEA) and the Nuffield Council. We have more recently made similar points to the US Food and Drug Administration (FDA).

We have also argued previously that the techniques involved are unsafe, unethical and unnecessary (see here, here, here and here).

British government hesitates on three parent embryos as international opposition mounts

The legalisation of three parent embryos for mitochondrial disease in Britain has been facing massive opposition all over the world with so far little response from Westminster.

But an answer to a parliamentary question this week gives the first sign that the government may be pausing to draw breath before implementing the new technique.

Apparently they are not going to proceed with three parent children regulations for now but rather have opted for yet another consultation.  

In response to a Parliamentary question asked this week by Lord Alton Government minster Earl Howe said that the Government will publish draft regulations as part of a public consultation shortly:

‘The Government is currently developing draft regulations, which will describe in more detail the proposed approach for regulating mitochondria donation treatment. The Government is planning to publish these, as part of a public consultation, shortly.’

I recently highlighted an article in Nature arguing that the UK’s decision to trial the technique is ‘both premature and ill-conceived’.

Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California had argued  in an piece titled ‘A slippery slope to germline modification’ that were the United Kingdom to grant a regulatory go-ahead, it would unilaterally cross ‘a legal and ethical line’ observed by the entire international community that ‘genetic-engineering tools’ should not be used ‘to modify gametes or early embryos and so manipulate the characteristics of future children’.

Christian Medical Fellowship has recently published a paper on ‘three parent embryos for mitochondrial disease’ which was strongly critical of this new technology on both theological and scientific grounds. 

This followed submissions that CMF made on the issue to both the Human Fertilisation and Embryology Authority (HFEA) and the Nuffield Council. We have more recently made similar points to the US Food and Drug Administration (FDA).

I have also argued on this blog that the technique involved is unsafe, unethical and unnecessary (see here, here, here and here).

Genuine concerns about this new mitochondrial technology have been swept aside in Britain in the headlong rush to push the scientific boundaries.

But in many countries around and the world, and by commentators from both secular and faith based scientific backgrounds, Britain is viewed as rogue state in this area of research.

Let’s hope that this hesitation means that the government is at last beginning to listen. 

UK decision to trial three parent embryos for mitochondrial disease ‘both premature and ill-conceived’ (Nature Magazine)

Christian Medical Fellowship has recently published a paper on ‘three parent embryos for mitochondrial disease’ which was strongly critical of this new technology on both theological and scientific grounds. 

This followed submissions that we made on the issue to both the Human Fertilisation and Embryology Authority (HFEA) and the Nuffield Council.

I have also argued on this blog that the technique involved is unsafe, unethical and unnecessary (see here, here, here and here).

I was therefore most interested to see these same views expressed this week an article in Nature arguing that the UK’s decision to trial the technique is ‘both premature and ill-conceived’.

Marcy Darnovsky (pictured) is executive director of the Center for Genetics and Society in Berkeley, California. In an article titled ‘A slippery slope to germline modification’ she points out that ‘those opposed to green-lighting mitochondrial replacement have been described in some quarters as religious objectors, against all types of IVF’.

However, she says, ‘many secular and actively pro-choice scientists, bioethi­cists and women’s-health advocates have voiced grave and detailed concerns about the safety and utility of mitochondrial replacement, and about authorizing the intentional genetic modification of children and their descendants.’

Were the United Kingdom to grant a regulatory go-ahead later this year, she argues, it would unilaterally cross ‘a legal and ethical line’ observed by the entire international community that ‘genetic-engineering tools’ should not be used ‘to modify gametes or early embryos and so manipulate the characteristics of future children’.

Darnovsky is very clear that ‘mitochondrial-replacement procedures would constitute ger­mline modification’.

She calls claims that such therapy would not affect a person’s identity ‘scientifically dubious’  and warns that ‘the permissive record of the UK regulatory authorities’ raises the prospect that inheritable mitochondrial changes would be used as a ‘door-opening wedge towards full-out germline manipulation, putting a high-tech eugenic social dynamic into play’.

To the claim that mitochondrial techniques would save lives, she points out that ‘these women have much safer alternatives, including pre-implantation genetic diagnosis and the use of third-party eggs with conventional IVF’.

She questions the HFEA’s claims that 1 in 200 children is born each year with a form of mitochondrial disease and the media’s uncritical acceptance of this figure, pointing out that the number is ‘more like 1 in 5,000’ (R. H. Haas et al. Pediatrics 120;1326–1333; 2007).

In addition she notes that among that much smaller group, a significant majority of cases involve mutations in nuclear as well as in mito­chondrial DNA, and so could not be helped by mitochondrial replacement.

Safety, she adds is ‘unproven’ and the results of animal trials are ‘far from reassuring’. Her overall assessment?

‘The question raised by these proposals is whether a risky technique, which would at best benefit a small number of women, justifies shred­ding a global agreement with profound significance for the human future. We need a moratorium on procedures based on human germline modification while that question is widely and fairly considered.’

Genuine concerns about this new mitochondrial technology have been swept aside in Britain in the headlong rush to push the scientific boundaries. But in many countries around and the world, and by commentators from both secular and faith based scientific backgrounds, Britain is viewed as rogue state in this area of research.

Three parent embryos for mitochondrial disease – unsafe, unethical and unnecessary

Britain is planning to become the first country in the world to offer controversial ‘three-parent’ fertility treatments to families who want to avoid passing on mitochondrial diseases to their children.

The BBC reports this morning on the new techniques which it is claimed will children born through 'three-person IVF' who would carry genetic material from each of three different people.

There are about 50 known mitochondrial diseases (MCDs), which are passed on in genes coded by mitochondrial (as opposed to nuclear) DNA. They range hugely in severity, but for most there is presently no cure and little other than supportive treatment.

It is therefore understandable that scientists and affected families want research into these two related ‘three-parent embryo’ techniques (pronuclear transfer and maternal spindle transfer) to go ahead. But there are good reasons for caution.

This is not about finding a cure. It is about preventing people with MCD being born. We need first to be clear that these new technologies, even if they are eventually shown to work, will do nothing for the thousands of people already suffering from mitochondrial disease or for those who will be born with it in the future.

There are also already some alternative solutions available for affected couples including adoption and egg donation.

But apart from this I’m left with four big questions.

Is it safe? This is far from established. Each technique involves experimental reproductive cloning techniques and germline genetic engineering, both highly controversial and potentially very dangerous. Cloning by nuclear transfer has so far proved ineffective in humans and unsafe in other mammals with a large number of cloned individuals spontaneously aborting and many others suffering from physical abnormalities or limited lifespans. Also, any changes, or unpredicted genetic problems (mutations) will be passed to future generations. In general, the more manipulation needed, the higher the severity and frequency of problems in resulting embryos and fetuses.

Will it work? I am sceptical. This technology uses similar ‘nuclear transfer’ techniques to those used in ‘therapeutic cloning’ for embryonic stem cells (which has thus far failed to deliver) and animal-human cytoplasmic hybrids (‘cybrids’). The wild claims made about the therapeutic properties of ‘cybrids’ by the biotechnology industry, research scientists, patient interest groups and science journalists duped parliament into legalising and licensing animal human hybrid research in 2008. Few now will remember Gordon Brown’s empty promises in the Guardian on 18 May that year of ‘cybrids’ offering 'a profound opportunity to save and transform millions of lives' and his commitment to this research as 'an inherently moral endeavour that can save and improve the lives of thousands and over time millions of people'. That measure was supported in a heavily whipped vote as part of the Human Fertilisation and Embryology Bill, now the HFE Act. But ‘cybrids’ are now a farcical footnote in history. They have not worked and investors have voted with their feet. Ironically, it was in that same Act of Parliament, that provision for this new research was also made.

Is it ethical? No, there are huge ethical issues. A large number of human eggs will be needed for the research, involving ‘harvesting’ that is both risky and invasive for women donors. How many debt-laden students or desperate infertile women will be exploited and incentivised by being offered money or free IVF treatment in return for their eggs? How many thousands of human embryos will be destroyed? If it ever works, what issues of identity confusion will arise in children with effectively three biological parents? What does preventing those with mitochondrial disease being born say about how we value people already living with the condition? Where will this selection end? Some mitochondrial diseases are much less serious than others. Once we have judged some affected babies not worthy of being conceived, where do we draw the line, and who should draw it?

Is the debate being handled responsibly? No. The research scientists involved have huge financial and research-based vested interests and getting the regulatory changes and research grants to continue and extend their work is dependent on them being able to sell their case to funders, the public and decision-makers. Hence their desire for attention-grabbing media headlines and heart rending (but highly extreme and unusual) human interest stories that are often selective about what facts they present.

It must be tempting for politicians to make promises of ‘miracle cures’ in years to come which no one may remember. But I suspect it is much more about media hype than real hope.

This new push is being driven as much by prestige for government, research grants for scientists and profits for biotechnology company shareholders as anything else.

Let’s keep a cool head and instead concentrate on finding real treatments and providing better support for affected individuals and their families rather than spending limited health resources on unethical, risky and highly uncertain high tech solutions that will most likely never deliver. 

 (See BBC, Guardian, Times(£), Independent, Daily Mail and Telegraph).

Three-parent embryos for mitochondrial disease? Twelve reasons for caution

The media is buzzing today with the news that Britain is planning to become the first country in the world to offer controversial ‘three-parent’ fertility treatments to families who want to avoid passing on mitochondrial diseases to their children (See BBC, Guardian, Times (£), Independent, Daily Mail and Telegraph).

The Department of Health announced yesterday that it would draw up draft guidelines to allow fertility clinics to offer the technique. The proposed guidelines would be released for public comment later this year, and Parliament would vote on a final version in 2014.

Scientists are currently researching two main three-parent IVF techniques. The first, being developed at Britain's Newcastle University and known as pronuclear transfer (PNT), swaps DNA between two fertilised human eggs. Another, called maternal spindle transfer (MST), swaps material between the mother's egg and a donor egg before fertilisation.

The BBC is heralding it as a ‘ground-breaking technique for preventing serious genetic disease’ and a ‘bold step for science and society’. Media reports are full today of reassurances that that mitochondrial DNA only accounts for 37 out of our 20,000 human genes and that this therefore is a small step that will be undertaken only under ‘strict safeguards’.

Most people accessing broadcast media will hear heart-rending accounts of affected families and will get the message that those opposing the move are Luddites and religious fundamentalists on the lunatic fringe.

But there are actually very good reasons we should not be going down this route. Here are just twelve for starters:

1. Even were this new technology to work (and there are huge questions about that) it would help only a very small handful of families and only a tiny fraction of those with mitochondrial disorders. One in 6,500 babies is born with mitochondrial disorder, about 200 per year in Britain. But only five to ten of these have conditions serious enough to merit this intervention.  The technology will not help the other 190 or the 12,000 people in the UK already living with mitochondrial disease.

2. Babies with serious mitochondrial disease will still be born as many families are not aware they are even carrying the abnormal genes until after the birth of at least one affected child. So this will largely be relevant only in preventing the birth of subsequent affected children to these families.

3. There are already alternative routes for these families to have unaffected children either through adoption or egg donation (although I personally have serious ethical misgivings about the latter).

4. Both techniques above involve cell nuclear replacement ‘cloning’ technology which has not yet been shown to work in humans. Whilst it appears to be effective in lower mammals like mice (see here) use of cloning techniques in higher mammals has resulted in huge numbers of miscarriages and the birth of large numbers of abnormal offspring. It took 273 attempts to produce Dolly the Sheep and she herself was abnormal dying early. There is a strong possibility that we may simply be trading mitochondrial disease for other abnormalities if babies are ever born after use of the technique.

5. It is likely that thousands of embryos will need to be produced and experimented upon in developing these techniques. Many, like me, who believe that human embryos are worthy of the utmost respect and protection as early individual human lives will argue that the end of producing an unaffected baby does not justify these means.

6. Tens of thousands of eggs will be required for this research. It is virtually certain that donated excess eggs from those undergoing fertility treatment will not be adequate to meet this demand and that egg harvesting from paid donors will be necessary leading to exploitation of  vulnerable women and exposure to  at times high-risk egg-harvesting procedures.

7. If successful, this research will cross an ethical and safety rubicon by allowing human germline genetic therapy for the first time in human history. The genes from the third parent will be passed on down the generations and will be impossible to remove from the family.

8. Any babies resulting from this therapy will have a third genetic parent whose details will not be on the birth certificate. This raises issues of personal and family identity for children born as a result of the technique and will inevitably lead to litigation involving parents wanting to assert maternity rights and children wanting information about all their genetic parents. Behind these cases will be the hugely emotive issues of custody and inheritance.

9. Allowing the technique will lead to further demands for extension in two ways. It will be argued that if we have accepted germ line therapy for mitochondrial disease then we should also accept it for genetic disorders transmitted by nuclear DNA and for less serious mitochondrial disorders. This will lead to pressure to extend the use of these techniques to other diseases. By backing germ line therapy even in these limited circumstances the UK is crossing a line that every other country which has considered the matter has concluded is too dangerous.

10. These techniques do not offer support or treatment to people affected with mitochondrial disease but rather are aimed at identifying these individuals at the embryo stage and genetically engineering them. There is more than an element of eugenic thinking here. Is it right for us to decide that lives with serious disability are not worth living to the extent that such people must be prevented being born or genetically altered to make them acceptable? This is a very dangerous slippery slope indeed.

11. In addition to genuine compassionate concerns about affected families there are very powerful ideological and financial vested interests in this field including research grants for scientists, profits for biotechnology companies and prestige for the British government. 

12. Hard cases do not necessarily make good law or policy. I remain deeply suspicious of the way this 'breakthrough' that will potentially help only a tiny number of people with a very limited number of conditions is being  foisted on the British public using emotive personal stories by an incredibly well-organised coalition of politicians, biotechnology companies, journalists, research scientists and patient interest groups without full consideration of the concerns like those above which many have expressed. I suspect there are much bigger agendas here that are not yet being fully disclosed. Are we, for example, seeing reproductive cloning and germ line therapy being deliberately smuggled in under the back door under the guise of compassion? The moving boundaries and mission creep we have seen with other IVF-related technologies should sound a huge note of caution for us. 

I have written previously on mitochondrial disease here, here, here and here. Also see CMF’s official submissions to the HFEA and Nuffield consultations on this issue and  a recent blog post where we argue that these techniques are unsafe, unnecessary and unethical.