Research approved for two-mom one-dad embryos
[Crossposted from GeneticFuture.org]
Scientists at Newcastle University have been given approval for new research aimed at combating a particular set of inherited human diseases: those that are passed on via mitochondrial DNA instead of the nuclear DNA most folks are familiar with. The trick? They’ll be creating human embryos that are the product of two mothers and one father. Here’s the background:
Nuclear DNA includes thousands of genes, and is given credit for making you who you are, and is in fact the only DNA considered when discussing the human “genome”. Mitochondrial DNA (MtDNA) only has 37 genes and doesn’t change much from individual to individual. However, that doesn’t mean that MtDNA isn’t capable of expressing diseases of its own.
So if you’re a mom who suffers from a mitochondrial disease, how do you keep from passing it on to your baby? According to the Newcastle researchers, here’s what you do: extract healthy ooplasm (including MtDNA) from a different mom’s egg cell and insert it into one of your own egg cells. Then fertilize it with the father’s sperm in the usual way (with glass rods and tubes and such) and presto! Healthy baby.
Trigger-finger ethics watchdogs suggest that you’ve just broken a new taboo — making an embryo that has two moms and one dad. Supporters would respond by saying that the nuclear DNA is the only “important” DNA, so who cares if the mitochondrial DNA comes from someone else?
Myself, I’m on the fence with this one. Most people would agree that there’s something ethically suspicious about making better babies by combining nuclear DNA from two moms. And while mitochondrial DNA doesn’t obviously code for things like blue eyes or long limbs, it does interact with nuclear DNA, working together for the expression and use of certain proteins. Will we discover some day that the rare and small differences found in MtDNA somehow have subtle (or profound) effects on the human phenotype — who we are and how we behave? If so, then mixing one mom’s DNA with the another mom’s MtDNA could lead us into ethically uncertain waters.
On the other hand, why not go for broke? Let’s use a surrogate mother for the womb too. Then we’ll have three mothers involved in the production of a newborn! Just imagine the positive impact such practices could have on profits on Mother’s Day… :)
[ Reference: BBC News ]
a few years ago there was talk that a propensity longevity was passed via the mtDNA because of variation in DNA replication fidelity in different lineages.
Will we discover some day that the rare and small differences found in MtDNA somehow have subtle (or profound) effects on the human phenotype — who we are and how we behave?
Obviously there are. These heritable mitochondrial diseases are an obvious example.
Wouldn’t you expect mtDNA diseases to die out pretty quickly, since reproduction is asexual?
“Most people would agree that thre’s something ethically suspicious about making better babies by combining nuclear DNA from two moms….”
I always found this kind of thing puzzling. I know there’s a lot of visceral hatred out there against the idea of improving humans genetically in any way (except perhaps choosing a good mate and hoping for the best), but I have never understood the *ethical* problem.
The only ethical problem I can think of here is a concern that the maternal instinct will be weaker if the mother knows the child isn’t 100% (or rather 50%) hers.
This research has been attacked by organisations describing themselves as ‘pro-life’, i.e. anti-abortion Catholics.
What could be more ‘pro-life’ than creating healthy babies rather than babies with serious metabolic illness?
I’m afraid I have no problem with this. Mitochondria are such a small part of the human genome. If the only way you could have a normal child is to take the mitochondria from someone other than the mother then I would jump at the chance.
I do have one question though… Wouldn’t it have been less controversial if they had taken healthy mitochondria from the father? After all, he already contributes around 50% of the nuclear DNA. What difference would the extra fraction make?
Men normally carry their mother’s mitochondria, but don’t ordinarily transmit them. I would think that you could always extract the father’s mitochondria from muscle cells for instance.
For my part, I wouldn’t have a problem with it if it were a *larger* part of the human genome, or if the donor strands were synthesized with no human donor at all. I mean, good parents do everything they can *after* a child is born to enhance its abilities and keep it safe – where is the evil in using advanced technology to accomplish the same thing earlier?
ercenary.com/d/20010211.html ).
(though this isn’t exactly what I have in mind: http://www.schlockm
Dan Dare: ?Men normally carry their mother’s mitochondria, but don’t ordinarily transmit them.?
What is the transmission rate? One in a thousand? Sperm are much, much smaller than egg cells. Is the relative contribution just the size ratio? How might paternal contribution of mitochondria distort mtDNA analysis of maternal lines?
Inside the cell, mitochondria continually merge and split. How often would genes be exchanged between the paternal and maternal mitochondrial plasmids? Over many generations there might be some limited exchange of genetic material across lines. (Or it might theoretically happen but would it be ruled out due to low probability?)
On the other hand, the mitochondria plasmid might not exchange genes. Also repeated cell division with random distribution of mitochondria at each division would reduce mitochondrial diversity. So all the mitochondria in a fertile egg cell might have identical genetics even if a fertilized egg had mixed mitochondria.
Will we discover some day that the rare and small differences found in MtDNA somehow have subtle (or profound) effects on the human phenotype — who we are and how we behave? If so, then mixing one mom’s DNA with the another mom’s MtDNA could lead us into ethically uncertain waters.
Uhmm – this is a little off topic but isn’t it a little grandiose to say that “who we are” == “human phenotype”? I’m always on the look out for is-ought conflationists – the sort who believe that the descriptive business of science has become the prescriptive business of morality (which is why imho “professional ethicists” are professional is-ought conflationists).
Wouldn’t it be more accurate to say that given enough phenotypes exhibited by human beings you can describe, at a given level of abstraction, what the human is made of? When put like that the idea that a descriptive discovery can implicitly create an ethical quandary is harder to stomach.
It also deprives the professional describers, practicing researchers, of any increased moral authority vis a vis their descriptive speciality.
If anything, someone who has foregone so much in terms of money, time, energy, family and the like in exchange for whatever it is they do get out of professional description – that person’s views on the ethical implications of their life’s obsession should, until shown otherwise, be viewed with extreme care. Much more care than, say, the average used car salesman explaining the benefits of a car he’s trying to sell you.
Interesting questions Fly.
I wouldn’t be surprised if sperm occasionally transmit their mitochondria to the egg. I wonder what happens. Do they fight for territory with the mother’s mitos? Does the egg expel/repel/kill the foreign mitochondria? The ultimate manifestation of the battle of the sexes. I guess females usually win. Just be grateful there’s no lawyers involved.
Dan,
I found the following article that addresses this topic. I suggest reading the whole paper as I?ve left out some interesting stuff.
http://www.pnas.org/cgi/content/full/93/24/13859
?In vertebrates, inheritance of mitochondria is thought to be predominantly maternal, and mitochondrial DNA analysis has become a standard taxonomic tool. In accordance with the prevailing view of strict maternal inheritance, many sources assert that during fertilization, the sperm tail, with its mitochondria, gets excluded from the embryo. This is incorrect. In the majority of mammals including humans the midpiece mitochondria can be identified in the embryo even though their ultimate fate is unknown. The “missing mitochondria” story seems to have survived and proliferated unchallenged in a time of contention between hypotheses of human origins, because it supports the “African Eve” model of recent radiation of Homo sapiens out of Africa. We will discuss the infiltration of this mistake into concepts of mitochondrial inheritance and human evolution.?
?
?The typical mammalian sperm midpiece contains approximately 50-75 mitochondria with one copy of mtDNA in each. This represents an 8- to 10-fold decline in copy number during spermiogenesis (15). In contrast, the mammalian oocyte contains around 100,000 (105) to 100,000,000 (108) mitochondria (16), and the human oocyte in particular is estimated to contain 100,000 (105) copies of mtDNA (17). Thus the oocyte’s mtDNA copy number exceeds that of the sperm by a factor of at least 1000 (103).?
?
?Intriguingly, the oocyte’s mtDNA derives from a very small pool (perhaps as few as five) precursor mitochondrial genomes during oogenesis. This selective pressure may serve as a selective genetic filter against defective mitochondrial genomes, just as it may explain why some intergenerational changes may occur so rapidly (18, 19).?
?
?However, there can be no doubt that at fertilization paternal mitochondria do enter into the ovum (Fig. 1). We do not know what really happens to them in subsequent development in most vertebrate species.?
?
?This error of obligatory maternal inheritance of mtDNA in humans appears to arise entirely from approaches using restriction fragment analysis (44, 45). However, Gyllensten et al. (46), using the PCR, detected paternally inherited mtDNA molecules in mice at a frequency of 1 in 10,000 (104), relative to the maternal contributions. They concluded: “Paternal inheritance of mtDNA also means that mtDNA phylogenies are not exclusively matriarchal.” [Note that the paternal inheritance rate of 1 in 10,000 (104) is that to be expected by simple dilution.]?
?
?We simply do not yet know what happens to the paternal contribution of mtDNA in humans, but the simplest explanation is that it is diluted beyond recognition by researchers using relatively low resolution techniques of molecular biology. We do know that paternal mtDNA enters the oocyte at fertilization. Models of human evolution using mtDNA analysis must take these facts into account. All theories of the timing of human evolution that depend on the premise that the sperm midpiece does not contribute to the embryo must be reevaluated or rejected.?
Thanks Fly,
Interesting and informative paper.
I often wonder if the proverbial dislike of mothers in law for their daughters in law doesn’t originate from the subconscious hate to “the one who will extinguish my mtDNA in my progeny line”, especially intense in those motherw who have only son(s).
Just another selfish gene manifestation…
About the inheritance of paternal mtDNA: there is some speculation that it gets tagged and subsequently destroyed (I’m not exactly in the area, so I cannot judge if its likely or not).
ience.wiley.com/cgi-bin/abstract/104086787/ABSTRACT
“Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals” from Microsc Res Tech. 2003 May 1;61(1):88-102 (abstract: http://www3.intersc
About the ethics of mtDNA from another mother: why not view it as organ donation (organelle donation)? Granted, the difference is still that mtDNA gets transferred to the next generation. But wouldn’t the mtDNA from a close (female) relative be quite similar to that from the “nuclear-DNA” mother? And then the difference wouldn’t be that large…
This is certainly an interesting twist to the IVF, surrogate mother, human cloning saga.
I greatly doubt that the use of another female’s mtDNA would have any affect on maternal bonding, though.
Finally, making better babies through a combination of genetic material is what we aim to do every time we procrate by choice. While I am averse to tweating genetic material to get babies with blue eyes, and suspicious for many reasons about human cell nuclear transfer used for reproduction, this method seems only slightly more invasive than egg donation and IVF.
As a highschool student I now have the intellect to understand the fact that although many transgenic experiments as well as cloning have costs and benefits.
There are many benefits to transgenics that are already in use today. Many people do not see this but in fact they do exist. I believe that even though there are serious dangers (for example: creating a super bacteria before ‘its time’) but we need to improve ourselves, as a species the reason why we survived to dominate earth is widely speculated. Many say that the reason we survived was because we didn’t specialize. I agree with this. However a cost of not specializing is not to adapt (to an extent) to any specific environment which leaves us open for many diseases and other problems that could have been avoided by specializing but since we didn’t we survived longer using the tools around us. In effect saying that using our technology is to say that we should have never used tools to begin with. Our basic instinct is to survive. It requires much mental force to break that. Nevertheless, if our instinct is to survive then why would we concern ourselves with blocking our future course?
I am going to catch some major fire for this but i now realize that what is stopping us is religion to some extent. Sure religion teaches our moral values and such but to say that we should give up our right to live so that someone elses beliefs can be appeased is pure madness. My grandfather has parkinson’s disease, and for the record im not striking this for pity using the Michael J. Foxx (check the last name plz) story that is unfolding at the moment, and i believe that stem cell research is a viable option for life and to extend our own. Now although we may think that these experiments are grizzly for taking a life of an unborn child, however, thanks to the many frankenstienian experiments by scientists studying electricity we now have the ability to restart a heart after it stops (part of the time). Religion is what is stopping us from utilizing our options because of the fact that they appease their religion in their beliefs (which again loops to religion) if we (being the U.S. (I know this is the world wide web so plz)) actually separated church and state like our constitution stipulates we would go farther into life saving technologies