Genetic engineering with the germ line


Some years ago, I attended a seminar at our university on the ethics of genetic engineering. The panel of experts spoke about the new ability to modify the genes of people with genetic disorders in order to remove the cause of their ailments. Even when they successfully cured the child of an inherited disease, the treatment did not prevent the child from passing on the defective gene to their offspring.

During the Q/A I asked why it was that the children who inherited the disease could be treated and cured with this very expensive treatment but that they did not modify the genes of the parent who had the disease-carrying gene to prevent the disease being passed on to the offspring in the first place. Surely that would be more cost efficient since you would have removed the threat of that disease once and for all in that particular family line.

The ethicists on the panel said that this was a bright line that should not be crossed, that while you could modify the cells of a person, you should not interfere with the germ cells that carry the genetic information to the next generation because then you would be essentially opening the door to creating new types of people and that would be dangerous.

I now learn that that bright line has been crossed. Scientists have been able to create human embryos in which defective mitochondria in a human egg have been replaced with that from a donor. As a result, for the first time, human embryos have effectively three biological parents, inheriting DNA from the mother, father, and donor. The article explains why this was done.

[Mitochondria] are also implicated in a wide range of more common diseases affecting children and adults, such as multiple sclerosis and Parkinson’s disease. Mitochondria have their own DNA and are inherited only from the mother, so replacing defective mitochondria in eggs from mothers who have a high risk of passing on such diseases could spare the children.

The new genetic line will be perpetuated down through the generations and this is what causes ethicists to express alarm.

“That kind of genetic engineering has been ruled off-limits,” says Marcy Darnovsky of the Center for Genetics and Society. “And it’s a very bright line that has been observed by scientists around the world.”

There have been lots of reasons for that line. One big one is purely practical, says Dartmouth bioethicist Ronald Green.

“If we make mistakes, we’ll effectively be introducing a new genetic disease into the human population — for generation after generation,” Green says.

But beyond the risks, Green says taking that step has long raised more far-reaching fears. It’s the kind of technology that could be used to try to create genetically superior humans.

“It could easily move into the realm of gene enhancement,” Green says. “Higher IQ. Improved physical appearance. Athletic ability. That’s a worry to some people — to many people.”

Some of you may have seen the futuristic 1997 film Gattaca. In it, ambitious parents would create several fertilized eggs that would grow to the blastocyst stage and be examined for their genetic potential, and of them select only those with superior qualities to be implanted in the womb. But in that fictional scenario, you could select from just a small set of naturally produced DNA. What is being done here goes well beyond that, to the creation of entirely new genetic lines.

Comments

  1. slc1 says

    I don’t want to play geneticist here as I have no expertise in that scientific discipline. However, it is my understanding that mitochondrial DNA exists outside the nucleus of the cell. My information is that virtually all the usual genetic information that builds the body comes from the nuclear DNA in the nucleus of the cell, half of which is inherited from the father and half from the mother. Thus, it is not evident to me how making minor modifications in mitochondrial DNA in the mother’s egg could be used to develop “super-humans”. Obviously, such modifications to the nuclear DNA would have more far reaching effects. Perhaps a reader with more expertise in the subject then I could comment on it.

  2. prochoice says

    I have never understood why this topic is called controversial –
    until this presidential election.
    A political movement like the teabaggers, which tries to do away with each and any choices women can make (and of course the right to have no child, for whatever reason including genetic disease) will, as a matter of course, also prevent people from having children and grandchildren who are as safe as possible from predictable diseases.
    Rightwingers as well as their candidates have expressed that they are willing to force women to have rapists´children,
    so in their logic/ethics/morals to make suffer as much as possible why should there be ANY disease prevention?
    Same emotions as the antivaxxers entertain.

  3. says

    Because I feel like putting my biochem degree to some use… Fun facts about genetics!

    Males always get more DNA from their mothers because the Y is significantly smaller then the X.

    Repetitive elements on chromosomes could also skew the 50:50 thing in women as well as each pair of chromosomes probably don’t have the same number of repeats.

    And of course mothers give the mitochondrial dna so they generally give more DNA to the child.

    I say generally cause we haven’t even considered the cases where people end up with extra chromosomes from one parent or the other.

    But that’s all kind of quibbling and my trying to justify my degree.

    ——-

    But to your actual point. I think its seen as something of a stepping stone. The mDNA is a much smaller segment of DNA then those in the nucleus and which should make it easier to map, have less likely hood of your replacement gene stuck somewhere you didn’t want it etc. Still if you have a technique for affecting germ line mDNA its no longer a huge leap to get to modifying the DNA in the nucleus. Sort of like how having rocket tests and enriched uranium does not a nuclear weapon make but its a good start towards one.

    Realistically speaking though affecting the nuclear DNA wouldn’t necessarily have a bigger difference either. How would fixing a gene coding for a protein in the mitochondria be significantly different then say swapping in a gene to fix sickle cell anemia or cystic fibrosis. While there are genes in the nucleus that would have more far reaching effects there are also plenty of other genes that could be modified to cure a genetic disease without any large scale (tv genetics third eyes) effects at all really.

    —————

    As for my own reaction to this its well mixed. Genetic engineering is a technology like any other technology. We can use our knowledge of it to combat human disease or create super humans and inequality and so forth. Its very hard to actually destroy something like this and its probably going to come sooner or later. The real question is how can we make society as a whole use this new tool responsibly.

    Just because someone tells stories of how fire can destroy your home doesn’t mean you shouldn’t make a fire. It only means that you need the wisdom to use fire safely.

    ————

    As to why you don’t just fix it in parents to cure it (aka the problem with eugenics). Its kind of a never ending battle. There are mutations that occur in creating the gametes for example that such that you could never really cure say Cystic fibrosis because even if you treated every one alive today carrying it you’d still just have new mutations occurring creating new carriers in children whose parents never had it.

    You also run into issues with creating a race gattaca super men. Assuming they can cross breed with non modified humans you’ll end up with their new genes entering the gene pool and dispersing and not really creating a race of supermen as some scifi shows. In order to perpetuate such a race you’d need to induce the kind of specification event (adding a pair artificial chromosomes ?) so that they couldn’t cross breed back into the original humans. Even still you’d just be isolating them from bad genes entering in from non modified stock and you can still have new deleterious genes been created naturally.

    In the end you’d have to go with a gattaca style world where everyone’s dna is tested and all babies were test tube babies to actually cure something this way. You could of course significantly hamper some diseases without going that far though by treating carriers or just testing in utero and aborting children that also carry the gene. OK I think that fulfills my biochemistry needs for the day ;p

  4. Jockaira says

    Green says taking that step has long raised more far-reaching fears. It’s the kind of technology that could be used to try to create genetically superior humans.

    “It could easily move into the realm of gene enhancement,” Green says. “Higher IQ. Improved physical appearance. Athletic ability. That’s a worry to some people — to many people.”

    Hey! Step back from that gene-splicing machine. We can’t be messin’ with God’s Creation. That would be blasphemy!

    It’s more important to adhere to God’s Plan than to improve life for humans. After all, He intended for us to suffer so that we would find immense relief and joy when we join Him at his side in Heaven.

  5. lsamaknight says

    All I can say is that while I’d personally prefer the man/machine interface route, this makes my inner Trans-humanist a happy little camper.

    Bring it on!

  6. invivoMark says

    You are pretty much correct. You couldn’t do much to the mitochondria that would make us superhuman. They’re already pretty well optimized after millions of years of evolution.

  7. invivoMark says

    This is a case of a particularly bad slippery slope argument.

    Here’s the logic in a nutshell:

    We can cure disease X. Disease X is horrible, millions of people suffer and die from it, and we have a surefire, reliable way to permanently cure it. But we don’t want to, because later someone might modify trait Y, which would be unfair to people who can’t afford to modify trait Y.

    WTF?

    Cure the damn disease! Those people are suffering from our inaction, and those who perpetuate the slippery slope argument are the only ones who stand in the way of a cure! These “ethicists” ought to go personally explain to sufferers of Parkinson’s and MS, face to face, why they need to continue suffering.

  8. invivoMark says

    I should note, we can’t necessarily cure the above diseases with the mitochondria method. My comment should be taken as a hypothetical situation. Change it to match any diseases that actually can be cured with mitochondrial genetic alteration (or, for that matter, any genetic alteration at all).

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