In vivo zygote mitochonrial transplantation. Neat! This is going to add an interesting exception to matrilineal DNA testing in the future.
Another thought, what about three parent households engaging in IVF? Will this be an option to have 3 biological parents regardless of disease? How will we keep records properly? What are the legal consequences? Do mitochondrial parents need to pay child support?
The amount of mitochondrial DNA is tiny though (~0.1%, according to the article), and not particularly unique to any individual, since it is passed down lately unchanged apart from the occasional mutation. There's no point having 3 biological parents unless there's a bad mutation in the mother's mitochondrial DNA.
I'm not sure there's any point to it. I know a couple poly families and my own situation isn't far off. The kids have a similar relationship with their parents as two-parent kids do. What DNA they happen to have doesn't matter, outside the occasional teenage outburst.
That is the case in many poly families, and I feel pretty much the same, however some people actually care about stuff like DNA and lineage. Having that as an option for some folks would be pretty cool. For instance, in cases where one person is infertile, they can still donate mitochondria.
This is such an incredible breakthrough and a huge win for science and families alike, however its sad that despite decades of work there is still no cure for mitochondrial disease. But the chance to preventing it being passed on is still such a major improvement. Also it’s sad that only the uk is capable of doing this atm bc it was the first country in the world to introduce laws to allow their creation after a vote in Parliament in 2015, while other countries were debating that it would open the doors to genetically-modified "designer" babies
It is an incredible breakthrough and if it prevents disease then all well and good, but are our Administrative Systems set up to handle such an arrangement?
I am by no means a callous person, in fact, my therapist tells me I have a problem with too much empathy, and in no way do I wish parents to loose their children so young.
But what I am also not is a eugenicist, which is what this is, eugenics.
"Eugenics is a set of largely discredited beliefs and practices that aim to improve the genetic quality of a human population."
Now remember, first they are only preventing the chance of a baby being born with mitochondrial disease. But more importantly, these mitochondrial diseases are still evident in the human population because there is some survival advantage. This is what happens with sickle cell disease [1]. The sacrifices these babies make, dying so young, is a sacrifice for the survival of a genetic population. In the case of mitochondrial diseases, this favors the survival of female babies over male babies, or even the benefit of higher amounts of oxidative stess in the mother to fight off infection.
So by this method, even the female baby will be born without the Mitochondrial mutation. What will this mean for her?
"Accordingly, their model revealed that some mutations confer a net replicative advantage over unmutated (wildtype) mtDNA, causing the mutant mtDNA to proliferate within individual organisms."
We know so little and we are acting like we know everything. Humanity needs to stop thinking we are gods and accept our fates. Eugenicists thought they knew what the best genes were to survive, and this is no different.
Eugenics has always been a technological problem, not an ideological one.
If there was a cheap and cost effective way to edit your genes as an adult in a 100% safe way, then everyone would be doing it.
The reason why eugenics has a bad reputation is that there are incredibly low tech solutions that require an authoritarian surveillance state and such states have indeed existed and abused their powers in the past. I'm talking about forced sterilisation.
The first problem with these low tech approaches is that their models suck and aren't founded by actual genetics research. E.g. fascists defining their own ethnic group as superior over other ethnic groups.
The second problem is that they didn't just think that they were helping the people born through eugenics avoid diseases or become better people, they were thinking that people with the wrong genes shouldn't procreate or exist at all, because they are a waste of resources and therefore should be killed even if they somehow manage to deal with their complications.
But if we take a step back and start off with a higher level of technology and scientific progress, these concerns turn out to be meaningless.
If there is a gene that objectively causes a disease or harm and it can be identified reliably, then having children with that disease becomes morally questionable. This means some people are prevented from having children that they would otherwise want. However, if there is a technology that allows people to have children without the disease, then suddenly the opposite happens. It becomes a moral imperative to give them access to the treatment so that they can have children. In the extreme limit, no matter how bigoted an eugenicist is, he must always allow even the most "inferior" people (in his eyes) to have children and procreate. The discriminatory part of eugenics collapses into itself as if it never existed.
This then leaves the actual problems with eugenics: lack of genetic diversity and unforeseen consequences of unrestricted gene editing.
The solution to this problem would be to never implement precise genetic editing in the first place. Instead, whole chromosomes should be swapped out. This will increase genetic diversity by allowing a single child to have the combined genes of multiple fathers and mothers.
Clever. So they fertilize an egg from the mother and another egg from a donor with the fathers sperm. Then they yank out the donor/father “pro nuclei” and replace it with the pro nuclei from mother/father egg. Thus the child ends up with the donor’s mitochondria.
Wouldn't it be significantly easier to just use the donor's egg here ?
Or adopt?
This feels a bit narcissistic. If you and your partner determine you have genetic traits you'd rather not have, you have the option of not having biological children.
This just feels like it's going to open Pandora's box. You and your partner are short and near sighted, edit in some height and vision.
You're partner has ethnic traits they don't want to pass on ? Just edit those out.
This feels like something that's going to start well intentioned, but snowball into very strange outcomes.
God forbid this ever comes to America's profit driven health system. The rich would have the option to edit in "better" traits. Gattica here we come
I think it would be better to describe this as an ‘organelle’ transplant as it would be easier for people to understand and discuss. Yes there is a donor (egg) and yes the new child will pass on the mitochondria to her children. But calling it a 3 person baby is unhelpful and misleading as IMO mitochondria DNA is of a different category to chromosomal DNA.
> I think it would be better to describe this as an ‘organelle’ transplant as it would be easier for people to understand and discuss.
Unlike previous attempts, the donor mitochondria are not transferred into the mother egg. Instead the donor cell is denucleated, and the nucleus from a mother's egg is transferred into the denucleated donor cell. Consequently, there is a wide variety of donor specific material, which may influence the early stages of development and only "wash out" after a number of cell divisions.
> But calling it a 3 person baby is unhelpful and misleading as IMO mitochondria DNA is of a different category to chromosomal DNA.
How so? Arguably, mitochondrial genes are much more essential than most nuclear genes.
1. Mutations in any mitochondrial gene often have dire consequences, whereas variants in nuclear genes are much more frequent.
2. Mitochondrial DNA is the most expressed in pretty much any cell by a huge margin. Mitochondria express 13 (IIRC) protein coding genes and two dozen other RNAs. Those 30 odd genes often make up 1-5 % of a cell's whole transcriptome. Only genes coding for ribosomal RNA are more strongly expressed.
So mother and father contribute the nucleus, and donor egg has everything else-- which is a lot more than mitochondria.
DNA required by mitochondria are both in the mitochondria and in the nucleus. This seems to show there is no co-evolution of the two; or the genetic distance of the donor might matter.
Still TBD whether other problems arise. If they do, I wonder if the affected person has any ability to get medical records of the other subjects, to compare diagnoses or treatments, notwithstanding privacy protections.
My son Oliver was born with mitochondrial disease and was killed by conditions associated with it at the age of 19. Some of the people mentioned in the report here were involved in his diagnosis and care.
His life deteriorated from that of a normal, fun loving intelligent kid to an isolated bed-bound disabled teenager, fed by total parenteral nutrition and suffering a variety of awful complications. His eventual passing was cruel and brutal. I'm not sure we will ever get over it as a family.
This treatment does now at least offer me a glimmer of grandchildren (my daughter having decided she would not risk children of her own until now). It's a remarkable achievement.
If most diseases are caused by errors in DNA, cannot we make mandatory DNA screening, detect such errors, and warn potential parents not to make children? Eventually this could lead to these diseases simply disappearing, and studying invalid DNA sequences seems to be much cheaper than researching the treatment for the disease.
This might be a silly question: I understand the mitochondria from the mother's egg is unusable due to disease. Why do they need a 3rd person to provide one? Is there a reason they could take one from a father's cell?
> Mitochondria in human sperm contain no or very little DNA because mtDNA is degraded while sperm cells are maturing, hence they typically do not contribute any genetic material to their offspring.
I believe the simple answer (vs complicated truth) is that the donor cell, a fertilized egg, is in a state accepting a not-quite-formed nucleus. There are no male cells that can get into that state AFAIK, possibly excepting pluripotent stem cells that are somehow convinced to undergo ovogenesis.
The truth is of course much more complicated than my limited understanding.
Fascinating that you can replace the nucleus of a cell and it keeps working fine, given cells are so complex... I wonder what (if any) setup/precautions are required in the cell biology to make it work. And I wonder if there are genetic conditions in which it can't work (e.g. some sort of mismatch between genes and what's already present in the donor cell)?
I mean click-bait par excellence. No shit it would come from0.1% of someone else. Give me something like three headed baby, you know that enquirer stuff, just class it up. Theres like 10,000 research articles published every year, there’s gotta be some damn interesting speck in this business.
I live in Newcastle and it's great to see Newcastle Uni in the news. Bobby McFarland is an international authority on paediatric neurology and of course mitochondrial medicine - he is also a truly lovely guy and intimidatingly smart. Everyone talks about Great Ormond Street but the paediatrics stuff being done at GNCH is world class.
43 comments
[ 2.8 ms ] story [ 68.9 ms ] threadAnother thought, what about three parent households engaging in IVF? Will this be an option to have 3 biological parents regardless of disease? How will we keep records properly? What are the legal consequences? Do mitochondrial parents need to pay child support?
Absolutely not. This is in vitro:
>> The eggs from both the mother and the donor are fertilised in the lab with the dad's sperm.
In vivo would make no sense.
it's not possible, these are organelles that are too big to be taken up by your cells, unless you can magically teleport them somehow to each cell
Amazing the domino effect.
He's currently working in the genetic disease space: https://www.paediatrics.ox.ac.uk/news/former-uk-prime-minist...
I am by no means a callous person, in fact, my therapist tells me I have a problem with too much empathy, and in no way do I wish parents to loose their children so young.
But what I am also not is a eugenicist, which is what this is, eugenics.
"Eugenics is a set of largely discredited beliefs and practices that aim to improve the genetic quality of a human population."
Now remember, first they are only preventing the chance of a baby being born with mitochondrial disease. But more importantly, these mitochondrial diseases are still evident in the human population because there is some survival advantage. This is what happens with sickle cell disease [1]. The sacrifices these babies make, dying so young, is a sacrifice for the survival of a genetic population. In the case of mitochondrial diseases, this favors the survival of female babies over male babies, or even the benefit of higher amounts of oxidative stess in the mother to fight off infection.
So by this method, even the female baby will be born without the Mitochondrial mutation. What will this mean for her?
https://www.vanderbilt.edu/evolution/mitochondrial-dna-evolu...
"Accordingly, their model revealed that some mutations confer a net replicative advantage over unmutated (wildtype) mtDNA, causing the mutant mtDNA to proliferate within individual organisms."
We know so little and we are acting like we know everything. Humanity needs to stop thinking we are gods and accept our fates. Eugenicists thought they knew what the best genes were to survive, and this is no different.
[1] https://globalhealthnow.org/2024-06/how-sickle-cell-disease-...
If there was a cheap and cost effective way to edit your genes as an adult in a 100% safe way, then everyone would be doing it.
The reason why eugenics has a bad reputation is that there are incredibly low tech solutions that require an authoritarian surveillance state and such states have indeed existed and abused their powers in the past. I'm talking about forced sterilisation.
The first problem with these low tech approaches is that their models suck and aren't founded by actual genetics research. E.g. fascists defining their own ethnic group as superior over other ethnic groups.
The second problem is that they didn't just think that they were helping the people born through eugenics avoid diseases or become better people, they were thinking that people with the wrong genes shouldn't procreate or exist at all, because they are a waste of resources and therefore should be killed even if they somehow manage to deal with their complications.
But if we take a step back and start off with a higher level of technology and scientific progress, these concerns turn out to be meaningless.
If there is a gene that objectively causes a disease or harm and it can be identified reliably, then having children with that disease becomes morally questionable. This means some people are prevented from having children that they would otherwise want. However, if there is a technology that allows people to have children without the disease, then suddenly the opposite happens. It becomes a moral imperative to give them access to the treatment so that they can have children. In the extreme limit, no matter how bigoted an eugenicist is, he must always allow even the most "inferior" people (in his eyes) to have children and procreate. The discriminatory part of eugenics collapses into itself as if it never existed.
This then leaves the actual problems with eugenics: lack of genetic diversity and unforeseen consequences of unrestricted gene editing.
The solution to this problem would be to never implement precise genetic editing in the first place. Instead, whole chromosomes should be swapped out. This will increase genetic diversity by allowing a single child to have the combined genes of multiple fathers and mothers.
Or adopt?
This feels a bit narcissistic. If you and your partner determine you have genetic traits you'd rather not have, you have the option of not having biological children.
This just feels like it's going to open Pandora's box. You and your partner are short and near sighted, edit in some height and vision.
You're partner has ethnic traits they don't want to pass on ? Just edit those out.
This feels like something that's going to start well intentioned, but snowball into very strange outcomes.
God forbid this ever comes to America's profit driven health system. The rich would have the option to edit in "better" traits. Gattica here we come
> I think it would be better to describe this as an ‘organelle’ transplant as it would be easier for people to understand and discuss.
Unlike previous attempts, the donor mitochondria are not transferred into the mother egg. Instead the donor cell is denucleated, and the nucleus from a mother's egg is transferred into the denucleated donor cell. Consequently, there is a wide variety of donor specific material, which may influence the early stages of development and only "wash out" after a number of cell divisions.
> But calling it a 3 person baby is unhelpful and misleading as IMO mitochondria DNA is of a different category to chromosomal DNA.
How so? Arguably, mitochondrial genes are much more essential than most nuclear genes.
1. Mutations in any mitochondrial gene often have dire consequences, whereas variants in nuclear genes are much more frequent.
2. Mitochondrial DNA is the most expressed in pretty much any cell by a huge margin. Mitochondria express 13 (IIRC) protein coding genes and two dozen other RNAs. Those 30 odd genes often make up 1-5 % of a cell's whole transcriptome. Only genes coding for ribosomal RNA are more strongly expressed.
DNA required by mitochondria are both in the mitochondria and in the nucleus. This seems to show there is no co-evolution of the two; or the genetic distance of the donor might matter.
Still TBD whether other problems arise. If they do, I wonder if the affected person has any ability to get medical records of the other subjects, to compare diagnoses or treatments, notwithstanding privacy protections.
His life deteriorated from that of a normal, fun loving intelligent kid to an isolated bed-bound disabled teenager, fed by total parenteral nutrition and suffering a variety of awful complications. His eventual passing was cruel and brutal. I'm not sure we will ever get over it as a family.
This treatment does now at least offer me a glimmer of grandchildren (my daughter having decided she would not risk children of her own until now). It's a remarkable achievement.
https://en.wikipedia.org/wiki/Sperm
So the sperm’s mitochondria are degraded, and I guess, you don’t want somatic cell components for various reasons.
The truth is of course much more complicated than my limited understanding.