I did not want to comment in this thread as I am heavily biased and my opinion cannot be very objective, but let me just try to clarify some facts:
About me: I do have a mitochondrial disease. In some of my cells, my mitochondrial DNA is not complete. If you think about it as a circle, about one third of that circle is missing. It is called a "heteroplasmic single deletion mtDNA mutation".
1. The mitochondrial DNA, much like the nuclear DNA, is a blueprint for building bits and pieces of our body.
2. The mitochondrial DNA encodes parts that are necessary to build the electron transport chain, i.e., to derive energy from food. In the car analogy, it encodes parts of the core engine (spark, combustion chamber, etc); the last step in the whole metabolic process.
3. The mitochondrial DNA does not encode anything outside of the electron transport chain. So, no blue eyes, no blonde, no smart. Nada.
4. This law will allow some kids to have a normal metabolism and a normal life. Nothing more. Nothing less.
5. I am well aware that this will open lots of possibilities for future genetic manipulation, but bear in mind that mtDNA is much more simpler than nuclear DNA and they are two distinct entities, so this law has no application in the field of traditional (nuclear) genetic manipulation.
Fortunately you probably won't have to go more than another ten years or so with that condition before it can be treated via either allotopic expression [1] of mitochondrial genes (e.g. as demonstrated for the single gene mutation in LHON [2]), delivery of whole replacement mitochondria [3], or possibly protofection of an entire replacement mitochondrial genome, although that latter item seems to have stumbled to one of those funding-related halts so common in research [4]. The others are presently pursued, though by no means as aggressively as the potential benefits merit. Everyone need mitochondria repair, not just people with inherited or other global genetic defects of the mitochondria.
That´s also my understanding (and my hope). My bet is on heteroplasmic shift though. This will not actually "cure" the disease, but it will minimize its effects. Specifically, I am closely following the work with mitoTALENs [1]. I have no scientific background, but I find this route easier, both technically and legally. Note the Dr. Aubrey de Grey does not agree with me either [2] :)
[1] Mutation specific compounds that will locate and degrade mutant mitochondria. Once degraded, mutant mitochondria will go through the normal cellular housekeeping (apoptosis) http://www.nature.com/nm/journal/v19/n9/full/nm.3261.html
I agree that mitoTALENs look promising, as does some early work on delivering RNA to mitochondria so that the necessary proteins get made even in the absence of genes. That said, I'd have said the same about exploiting mechanisms in leishmania [1] to deliver useful molecules to mitochondria if you'd asked me five years ago. That line of work seems to be in the doldrums too at this point, not much progress to be seen.
The most promising sign is the metasign - that we can compare and contrast so many different approaches, and complain because some are not getting more attention. Yet overall things are happening.
Yeah, I feel kind of lucky these days, now that mitochondria seems to be at the center of every possible "aging" disease. Something good will happen sooner or later.
The next milestone is the approval of EPI-743[1]. Phase III trials have just finished and data is being gathered and analyzed. If everything works out fine, we could see actual prescriptions of the drug one year from now.
Speaking of LHON, take a look at the impressive results[2] of this drug with LHON patients.
>4. This law will allow some kids to have a normal metabolism and a normal life. Nothing more. Nothing less. //
I don't get it. Of course on a personal level we have a biological drive, like a hunger, to have children. But on a group level I don't understand why we find it necessary to satisfy that need?
The problem of children with mitochondrial problems being born, as in Bernardi's case in the article, could seemingly be solved by her having had a test to determine if she had mitochondrial disease (ie she would, in the future, qualify for this cytoplasmic transfer treatment) and then her not having biological children of her own. That would also rule out the potential for unknown complications later
To me our current population seems barely sustainable and we already have plenty of orphans in need of families to care for them. It doesn't add up.
Now, I'm sure if I were in the situation of this enabling me to have a biological family then I'd want it, that seems entirely natural. But objectively how does that benefit my community, country, the world?
First of all nobody is talking about enforcing anything, so the "you want to kill people!" slippery slope is out of the way. Second: where is the line then? If I have AIDS should I have children (and not get treatment to avoid infecting them)?, if you say "no" that is eugenics. I, myself, I'm carrier of a disease that I is mostly genetic, so I decided that I will never have children. Discouraging the (pre-) existence of unhealthy childs is not nazism and people should stop pretending it is.
You just confused Eugenics with Euthanasia which are completely different things.
Eugenics is reproductive control on a very high level, and may go even as far as governmental control on procreation.
Aside the ethical problems with Eugenics there's also a problem raising from simple statistics: In which way shall it be decided who may procreate with whom and who not? Any kind of biased selection eventually leads to a drop in genetic diversity. However the smaller the genetic diversity the higher the chance for illnesses and defects to spread within the population. So if the ultimate goal is genetic diversity the only sound selection would be to make as much mix-and-matches as possible.
Interestingly enough mitochondrial transplantation adds a little to genetic diversity, because it dissolves the meiosis relationship between female nuclear DNA and mitochondrial DNA.
(1) is it fair to prohibit someone from having one biological child, while others can have five or six, just because she got unlucky in the genetic lottery, assuming she can afford the procedure?
(2) assuming legalization, is the number of children born from parents with this problem really going to have a significant impact in the worldwide population levels? Isn't it like stopping bathing to save water while you continue to water your lawn every day?
Selection of those who are allowed to be most fecund seems to me like a natural extension of neo-darwinism. We've fallen in to a position where the human race has engineered in - by social and technical changes - the ability for those with low morals and low intelligence and low natural survivability to survive and reproduce. It's not like we've been neutral, we're already currently acting to alter the survivability of different traits in humans.
Luck doesn't seem to have a scientific basis. No one chose for the person to have an innate biological inability to produce healthy offspring whilst another person does have that ability [to a greater extent]. How is it not fair? Clearly being unfair is allowed as you said "assuming she can afford it", why should financial ability trump biological suitability? That doesn't seem fair nor sensible.
Will children born from parents who are otherwise unable to reproduce, due to their innate biology, contribute to global population increase over the long term? Well, yes, if we allow it to. Or as is suggested here, we choose it.
Use your shower water to water your lawn, make sure you're washing without chemicals that are going to cause a detrimental impact on flora, waterlife, groundwater and such.
To use your analogy I'd say choosing to enable the continued acceleration of global population increase is like legislating to guarantee the use of lawn sprinklers when there's a shortage of drinking water. Your analogy is twisted as without allowing this procedure to take place we will still have more people than we need to continue the human race [of course if we need more people in the future for colonisation of other planets, or whatever, then the argument may well change].
Luck doesn't seem to have a scientific basis. No one chose for the person to have an innate biological inability to produce healthy offspring whilst another person does have that ability [to a greater extent]. How is it not fair?
That she has an inability is not fair nor unfair; it simply is. That you chose to criminalize her decision to have children via this procedure is a choice, and in my opinion, it's unfair since it discriminates people and for no good reason.
I'm a fat, lazy slob, and I'm allowed to have children, and she isn't? That's simply wrong.
Clearly being unfair is allowed as you said "assuming she can afford it", why should financial ability trump biological suitability? That doesn't seem fair nor sensible.
Who says it should trump? As far as I'm concerned neither should be restricted from having children. You're the only one arguing for restrictions.
The idea of financial ability was merely to say that my position doesn't require others to pay for it.
Use your shower water to water your lawn, make sure you're washing without chemicals that are going to cause a detrimental impact on flora, waterlife, groundwater and such.
What "chemicals"? It's just a child like any other. We have no reason to believe it's more harmful than mine or yours. If she should prevented from having them, on what grounds shouldn't we prevented everyone else?
To use your analogy I'd say choosing to enable
Ah, but that's the thing. You view this as "choosing to enable". But nobody is asking you to enable anything; just to not throw people who decide to have the procedure done in prison (or fining them or whatever).
"engineered in the ability for those with low morals and low intelligence and low natural survivability to survive and reproduce"
On the other side, we've also engineered in the ability for societies with low morals and low intelligence and low natural survivability to thrive on foreign aid and green revolution and raw minerals export.
Maybe we should be fixing this from the angle of letting poor and inefficient cultures starve, rather that preventing more productive cultures reproduce?
The global population of 8 billion for the resources available on the planet in order to create sustainability going forward that will allow the planet to continue to sustain 8 billion people - and the greater number as death rates decline - for the foreseeable future.
According to Wikipedia, http://en.wikipedia.org/wiki/Demographics_of_Germany, Germany's natural population as deaths-vs-births has declined by up to 0.24% (-2.4 per mille listed on Wikipedia) per annum. However, the same page indicates that Germany has the largest migrant population - 10 million people - who are not in those figures.
I've not looked at their population stats in detail but first indications are that their population is not falling.
Natural population of European countries falling doesn't create extra resources on the planet.
Lets turn it around, explain why Germany need an increase in endemic population? How does that benefit the rest of us?
Endemic German population don't need to explain itself to "the rest of you" because it is self-sufficient and even generating substantial "revenue" being an industry locomotive.
On the other hand, endemic African population can't even feed themself and rely on foreign aid and still starve.
It is obvious that we should make sure stable and productive society remains stable. Yes, lifting Africa out of poverty is important, but more important is not kicking Germany into poverty.
Which might as well happen if we populate it with random starving people from that 8 billion and order them fed no matter what.
So, Germans are going to try to keep their endemic population and culture because they can and should. And the "rest of you" should probably learn how to survive without wasting precious planetary surface.
> Now, I'm sure if I were in the situation of this enabling me to have a biological family then I'd want it [...]
Personally, I wouldn't be so sure. Having kids is a leap of faith and involves risks no matter what you do, of course, but if I had a problem which a) prevented me from having kids without assistance and b) may result in unknown complications later for my child, I'm not sure I'd do it. At that point being a loving, generous, responsible parent may mean not being a parent at all (or adopting).
I'd have to know what the odds and severity of any potential problems would be in order to compare that to other (normal) genetic risks, though.
Population growth is an interesting phenomena. If you look at the end-game, we have a trend of industrialization and 3rd world countries industrializing. After a country has industrialized, birth rates tend to drop off, even past the point of sustaining population level. Population declines have many negative economic consequences.
I don't think you have addressed all the concerns in the article. You say
>4. This law will allow some kids to have a normal metabolism and a normal life. Nothing more. Nothing less.
But the objection of Dr. Morrow is that the procedure may have risks for the children involved (and their children also). Whenever there are risks as well as benefits, there needs to be a discussion as to what is ethical.
Fair enough, and I agree with Dr. Morrow. My post was more about not confusing "à la carte" kids with mitochondrial DNA manipulation. I have read too many articles that fall into the "blonde, blue eyes and smart kids" category. This law is not about this at all.
Maybe whole chromosome replacement can also be a starting way to cure some genetic diseases. In particular the Y-chromosome, which does not undergo recombination and so changes to it could be easier to predict.
Perhaps an expert could weigh in here, because I don't really understand the controversy.
The "third parent" provides mitochondria which, by my understanding, doesn't affect the genetic makeup of the baby. In other words, the parents' genes which form the nucleus are intact and unmodified. Isn't this more akin to receiving an organ transplant than genetic manipulation/selection? Or am I missing the point here.
The mitochondria has a genome (mtDNA). Not my area but I think while we initially thought it was a fossil of the mito's prokaryotic history and we'd subsumed all the good stuff, there are genes there that may be of interest for exploring ageing and metabolic disorders. It's also quite interesting genetically, as only passed down the maternal line, so can be traced back to a single "mitochondrial eve" (MRCA). This brings up some neat ideas in selfish gene theory wrt battle of the sexes etc.
As a point of interest, there have been some rare cases of mitochondria being passed down paternally, most likely due to incomplete destruction in the embryo.
Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. And it affects the General genomic characteristics of an organism.
You have to wonder how far people are willing to go to declare things defects. At first it's just serious diseases. But then people will want their children to have correct color vision and other nice things.
However, on the other hand, this could actually be a good direction to move in. We can not only eliminate genetic diseases, but also genes that predispose us to other common diseases like cancer.
And then someone isolates a gene that predicts homosexuality.
I'm a strong techno-optimist, and I think we should have an extremely open mind to the possibilities offered to us by these advances, and we should fight the tendency to fortify our little local maximum out of fear - but we also need to recognize that some really dangerous things lie ahead.
Look up (1) kin selection, and (2) sickle cell anemia for information on a couple ways by which genetic traits that can discourage those who have them from reproducing can persist and even thrive in a population.
But genes or not, I brought it up as an example of something that we're clearly NOT comfortable removing (even if we could), although there's still plenty of communities where not being gay "would for some reason improve the child's quality of life".
>But genes or not, I brought it up as an example of something that we're clearly NOT comfortable removing (even if we could)
Why are "we" clearly not comfortable with that?
Indeed, if "we" are all uncomfortable with that then we needn't worry about anyone doing it. You seem to be worried that some people are going to want to specify non-gay children but think they ought to have them anyway. For some reason.
On the other hand I admit it might make me queasy to think of parents deliberately engineering their children to be gay. As in "Oh honey, let's make our third child gay, it'll be fun!"
> On the other hand I admit it might make me queasy to think of parents deliberately engineering their children to be gay. As in "Oh honey, let's make our third child gay, it'll be fun!"
Yes, especially given the fact that the only reason people have children is because nature intends to replace the parents with their offspring, using rules crafted by natural selection, not the parents' tastes.
>nature intends to replace the parents with their offspring, using rules crafted by natural selection, not the parents' tastes.
In fairness, sex was invented at least 1.2 billion years before parents could have possibly had "tastes". The reason we reproduce sexually rather than just churning out clones of ourselves appears to be that we're more resistant to parasites/diseases if our genes keep constantly shifting into new combinations rather than hanging around for too long looking exactly the same.
This wouldn't necessarily be impacted by the parents' deliberate choice of a few specific alleles.
> The reason we reproduce sexually rather than just churning out clones of ourselves appears to be that we're more resistant to parasites/diseases if our genes keep constantly shifting into new combinations rather than hanging around for too long looking exactly the same.
That's certainly high on the list, but replacing one population with another on a regular basis is also on the list.
> This wouldn't necessarily be impacted by the parents' deliberate choice of a few specific alleles.
Of course it would. Evolution can be a complex topic, but there's one simple fact at the center -- nature knows more than we do. An organism's ability to survive, to prevail over other genotypes, speaks louder than any of our expressed tastes and choices. That means if parents make the wrong choices, nature will step in and correct them.
Nature doesn't intend. It accidentally achieves. There's no point trying to divine direction where none was given. Particularly since we are part of nature.
So? The world of GATTACA seemed pretty awesome. Everyone was smart and fit and healthy and good-looking.
In fact, life was so perfect that the writers had to postulate the existence of non-genetically-engineered people in order to have any drama at all. "Wouldn't it suck if you were born into this society without any genetic enhancement?" the movie asks. And the answer is: yeah, so you should genetically engineer your children.
I thought the whole point was that the main character got into space on merit, even though all the fancy genetic screening predicted that he wouldn't be able to. The human spirit of an individual triumphs over a short sighted and capricious society.
You mention the heart defect. In the movie, the heart defect is only genetically potential, it is implied that if the character had it they would be dead before the events of the film.
Sure, I guess I would refine it and say that he made it into space based on some standard of merit that I was defining, not based on the one the short sighted and capricious society defined.
Gattaca is just a scifi movie, not particularly good at science realism. We should not take guidelines for Artificial Intelligence research from the Terminator movies, and we should not take genetics guidelines from Gattaca.
Everyone should have the option of upgrading to better, damage resistant mitochondria, or the option to purchase effective maintenance of mitochondrial function. Some haplotypes are objectively better than others, allowing greater athletic ability or resistance to age-related disease, but we can go beyond even just picking haplotype.
Progressive damage to mitochondrial DNA is an important contribution to degenerative aging. Wholesale replacement of either mitochondria or mitochondrial DNA (via any one of four or five different approaches) is a very viable near term goal. All of the necessary component of such a treatment have been demonstrated in animals and human cells in the laboratory over the past decade, leaving just the painfully slow regulatory and development process.
> this could actually be a good direction to move in. We can not only eliminate genetic diseases, but also genes that predispose us to other common diseases like cancer.
But where does this stop? Replace a gene -> replace mitochondria -> replace a whole chromosome -> replace the sperm/egg -> replace the whole child. We've come back to the real world, i.e. adoption.
I'm not sure why you think adoption is at this end of the continuum. I would say that complete genetic engineering of a zygote "from scratch" would be at this end of the continuum. Somewhere in between would be selecting exactly which of your and your partner's genes go into the zygote.
Eugenics is one of those words steeped in 20th century baggage.
I think there is a parallel to geo-engineering. It sounds like it'll lead someplace troublesome. people can't be trusted with it. OTOH, we have international conferences where they're trying to reach some sort of decisions about how much carbon there should be in the atmosphere. Maybe they'll be deciding how warm it should be, or how much rain europe should be getting.
Once we have the ability to influence these things we are geo-engineers, eugenicists, etc. It's not a choice. Not any more than we chose to take horses, ship rats and house cats to every part of the world.
Most words that were not invented in the last 15 years are steeped in historical baggage. That doesn't mean that we should not learn from that history.
In fact, if people start inventing words for things that we already have words for it's a good time to start paying attention, likely you're being sold on something.
So because Hitler wanted to wipe out Jewish people we shouldn't suggest that those with hereditary genetic diseases don't have children, or for example make genetic tests available to those who are [hoping to get] pregnant?
All of these are called eugenics (though the first is not really focussed on genetic traits); pretending that "eugenics" doesn't carry any baggage because of it's association with Nazi Germany seems pretty disingenuous.
I think its more than just the words, it's the concepts themselves.
Eugenics is scary, morally complicated, exciting and possibly inevitable. It has some historical associations with fascism and 20th century modernism in general.
The whole thing make people uncomfortable. It's hard to criticize when people just get creeped out by the idea.
Any mention of eugenics makes me distinctly queasy as I learned from my mother in my mid 20s that I was almost aborted as an embryo on the recommendation of doctors as two of my older siblings are (mildy) physically disabled and they judged there was a risk I could suffer the same problem.
Fortunately for me, my mother's GP discussed the matter with her and actually argued against the recommendations of specialists and I turned out perfectly healthy.
This matter only came up in conversation when she mentioned that the GP in question had died and I said I had never liked him as a kid and she pointed out how ironic that was as he saved my life.....
The problem with any kind of structural attempt at removing undesirable traits/children with defects from the population before they are born is the false positive rates are very high. Fortunately for you you're here and healthy. The flip side is that you might not have been healthy and then there would be a significant burden on those around you and society. These are very difficult problems and the harshness and ease with which people talk about them and pass judgement are in stark contrast with what a more informed person would probably conclude.
The wikipedia article is particularly precise when it comes to articulating the problems stemming from slippery slope arguments around this subject.
In the end, Eugenics is a tool that can be used for good and bad, just like every other tool. But it needs very good oversight and the use cases displayed so far are not all positive in my opinion.
I don't get it why I am always getting voted done. And the parent poster of my comment obviously does not understand anything about what a disease is (feel free to give a definition without googleing it), why genetic variance exists and pleiotropic genes. But thanks for voting me down.
Hint: What a disease is and what not, depends a lot on the environment.
I suspect it was because your comment was quite unconstructive, and comes across as a mildly sarcastic taunt rather than a genuine question.
If instead you had explained why you disagree with the parent poster and offered some information on how best to define a disease, you most likely would not have been downvoted.
On a narrow view why have Dr Morrow's concerns been rejected if because his studies include lots of species but not humans. If, as the article says, there has been "a lack of funding" to do studies on the children who have survived following cytoplasmic transfer?
Isn't this an important enough issue to do a study?
Why would you say "there have been problems with all species undergoing this procedure who have been studied" and "humans having this procedure haven't been studied [in depth]" and conclude that the procedure was "not unsafe"?
It says The HFEA's scientific reviews dismissed Morrow's findings as not relevant to humans because they were done on inbred animals.
I think that the animals were inbred was probably important to that decision.
There's also a paragraph where another scientist says:
"Whereas the original techniques were used with only [experiments from] mice, rabbits, lab animals... the big difference here is we also have issue of human embryos and this work has been tested in macaque monkeys in primates. All those were very useful, reassuring… hence why we came to the conclusion that this is not unsafe."
So "there have been problems with all species" is not a fair representation of the information given in the article.
Agreed with your last sentence, I clearly skimmed over too fast - but that doesn't alter the conclusion for me; surely you'd want to actually look at the human subjects (at least) that resulted from this procedure in depth before concluding that it's not unsafe?
I tend to give people the benefit of the doubt. As it is, "not unsafe" is a pretty soft statement to make, it isn't a declaration that there will be zero problems, it just reveals a certain amount of confidence that the procedure will be successful in humans. Perhaps they could have found a better way of phrasing it, but I don't see it as intentionally misleading.
Just imagine that mitochondria are an API to a power system and the nucleus is the control system. Sometimes it works out that a foreign mitochondrial component (i.e. 3rd party) works well, or maybe there are even whole classes that work well. But we just don't know. Maybe they are directly swappable, but since we don't even understand all the processes that go on and what communication (exactly) takes place we can't say for sure, we just have to go on primitive black-box cohort studies.
I'd say you're massively selling current knowledge short. Of course in biology you can always go a level deeper and say "but how exactly... " however there's been a lot of research on mitochondria and there are entire centres that study it. In comparison to complex eukaryotic cells, the mitochondria have been see as relatively low-hanging fruit in terms of systems-level modelling (e.g. http://www.sciencemag.org/content/340/6140/1567) due to their simplicity as a regressed prokaryote with a short circular genome.
"Sometimes it works out that a foreign mitochondrial component"
Every embryo has 1/2 of genes foreign to mother's mitochondrias - with no gene or combination is guaranteed to be non-foreign.
If it doesn't cause problems, why would having all foreign genes suddently cause them?
About me: I do have a mitochondrial disease. In some of my cells, my mitochondrial DNA is not complete. If you think about it as a circle, about one third of that circle is missing. It is called a "heteroplasmic single deletion mtDNA mutation".
1. The mitochondrial DNA, much like the nuclear DNA, is a blueprint for building bits and pieces of our body.
2. The mitochondrial DNA encodes parts that are necessary to build the electron transport chain, i.e., to derive energy from food. In the car analogy, it encodes parts of the core engine (spark, combustion chamber, etc); the last step in the whole metabolic process.
3. The mitochondrial DNA does not encode anything outside of the electron transport chain. So, no blue eyes, no blonde, no smart. Nada.
4. This law will allow some kids to have a normal metabolism and a normal life. Nothing more. Nothing less.
5. I am well aware that this will open lots of possibilities for future genetic manipulation, but bear in mind that mtDNA is much more simpler than nuclear DNA and they are two distinct entities, so this law has no application in the field of traditional (nuclear) genetic manipulation.
Hope this helps.