Sunday, December 19, 2004

Scientists Seek To Create 'three-parent' Babies

This is old news by now, but it is something I sort of kept in reserve, to blog about when I got a round tuit. 

In October of this year (2004), New Scientist et. al. reported that researchers in the UK were developing plans to create human embryos with genetic material from three persons

This would be done by taking the nucleus from a woman's egg, transferring it to an egg cell from a second woman (which had had the nucleus removed), and fertilizing the resulting egg with sperm from a third person.  Since the  mitochondria in the egg carry a few genes, the resulting zygote would contain genetic material from all three people.  This would enable women who carry mitochondrial genetic disease to have children who would not be at risk for the disease. 

Any child born following implantation of such an embryo would have cells containing a nucleus with genes from both parents, and mitochondria from a woman other than their mother.

Normally, mitochondria are inherited from the mother via the egg. Turnbull and Herbert's research aims to help women who are carriers of a mitochondrially inherited disease, who may or may not suffer symptoms themselves, but have high levels of mutated mitochondrial DNA in their eggs. Using an egg cytoplasm donor would reduce the risk of passing on such diseases.
The procedure also could be used to increase fertility in persons who did not have a genetic disease, as reported in Nature.  However, the Nature article indicates that mitochondria transfer could be used to boost fertility even if the mitochondria were taken from the mother's own somatic cells.  That would not result in a person with three parents. 
The team carried out a first trial of the technique on women who had already failed to conceive with IVF. The researchers isolated cumulus cells, which normally nestle around developing eggs in a woman's ovary, and extracted the mitochondria from these.

They injected up to 5,000 mitochondria into each egg, 5% of the total number they already contain. The researchers then fertilized the eggs in the lab, allowed them to grow into embryos and implanted them into the woman's uterus.

Of 71 attempts, 35% soon resulted in a pregnancy and 20 babies were born, revealed team leader Chii-Ruey Tzeng of Taipei Medical University on 19 October. By contrast, only 6% of attempts without mitochondrial injection had previously resulted in pregnancy in the same group of patients, none of which had reached term.
So mitochondrial transfer does not have to involve the creation of three-parent babies, but it could.  It depends on the methodology used.  As is often the case with this kind of biotechnology, you really have to keep up on the details to understand what is going on. 

Various people have commented on the concept of three-person babies, and most seem to think it is no big deal.  Nouslife points out that it is not more morally complex than a blood transfusion.  Of course, blood cells have a limited life span, whereas the mitochondrial DNA would persist in all cells, for the entirety of the persons life.  It probably is more analogous to a kidney transplant, or a bone marrow transplant.  Still, I could not find anyone on the 'net who expressed opposition to the idea of a people carrying DNA from three people. 

In fact, we all carry DNA from millions of people, if you consider all of a person's ancestors. 

Randall Parker at Future Pundit  points out that perhaps 3-parent babies are just the beginning. 
In a broader context this is one step down a much longer road where children will be born who have many genetic parents. In the future with more advanced techniques for manipulating cells (perhaps using microfliuidics) the 23 pairs of individual nuclear chromosomes that make up a single cell's DNA complement could be taken from different people to combine in the nucleus of a single embryonic cell. That cell could then develop into a full adult. Once it becomes possible to extract and insert individual chromosomes the nuclear DNA for a single embryo could be built using chromosomes taken from 46 different people.

The ability to combine chromosomes from lots of different people is one of the ways that people will create kids who combine many different most desired features into individual people. This will have the effect of speeding up human evolution because as desired features are more rapidly selected for then of course less desired features will be just as rapidly selected against.
This is more morally complex, because it would not merely be a matter of restoring fertility, or of treating disease.  As Mr. Parker points out, it could increase the rate of evolution in our species.  The absolute amount of increase would be small, because not very many people would be able to afford to do this.  I don't see a problem with that, necessarily, although tampering with fundamental biological processes is not something to be undertaken lightly. 

What got me to look into this topic, though, was a comment left (by a regular reader, but I can't remember who) on CC a few weeks ago, pointing me to this article:
Scientists debate blending of human, animal forms
By Rick Weiss
Updated: 1:14 a.m. ET Nov. 20, 2004

In Minnesota, pigs are being born with human blood in their veins.

In Nevada, there are sheep whose livers and hearts are largely human.

In California, mice peer from their cages with human brain cells firing inside their skulls.

These are not outcasts from "The Island of Dr. Moreau," the 1896 novel by H.G. Wells in which a rogue doctor develops creatures that are part animal and part human. They are real creations of real scientists, stretching the boundaries of stem cell research.

Biologists call these hybrid animals chimeras, after the mythical Greek creature with a lion's head, a goat's body and a serpent's tail. They are the products of experiments in which human stem cells were added to developing animal fetuses.

Chimeras are allowing scientists to watch, for the first time, how nascent human cells and organs mature and interact — not in the cold isolation of laboratory dishes but inside the bodies of living creatures. Some are already revealing deep secrets of human biology and pointing the way toward new medical treatments.

But with no federal guidelines in place, an awkward question hovers above the work: How human must a chimera be before more stringent research rules should kick in?

The National Academy of Sciences, which advises the federal government, has been studying the issue and hopes to make recommendations by February. Yet the range of opinions it has received so far suggests that reaching consensus may be difficult. [...]
The United States of America, in fact, has a chronic problem with development of regulation of biotechnology.  Some of the issues are so complex, and so politically hot, that politicians are loathe to even start addressing them.  As Mr. Bush found when trying to develop regulations for embryonic stem cell research, any compromise reached is going to alienate some people.  As a result, entire areas of biotechnology are proceeding without federal oversight. 

The mitochondrial DNA thing is not very troubling to people, because, as far as we can tell, none of the genes coded into mitochondrial DNA has anything to do with personality or behavior.  Although there are small variations in those genes, they all function pretty much the same way, no matter what animal they come from.  It is sort of like taking a bolt out of a Chevy engine, and putting it into a Ford engine.  No big deal. 

Chimeras, though, represent a more fundamental change to the organism.  There even is evidence that behavior can be affected:
The potential power of chimeras as research tools became clear about a decade ago in a series of dramatic experiments by Evan Balaban, now at McGill University in Montreal. Balaban took small sections of brain from developing quails and transplanted them into the developing brains of chickens.

The resulting chickens exhibited vocal trills and head bobs unique to quails, proving that the transplanted parts of the brain contained the neural circuitry for quail calls. It also offered astonishing proof that complex behaviors could be transferred across species.
 Some people might be troubled by this kind of thing.  I haven't yet run across a cogent, detailed moral objection to it, although some bloggers have expressed repugnance:
First of all, there's clearly a difference between organ transplants (even cross-species organ transplants) and actually growing parts from one species in another species.  To fail to recognize the huge difference is a big mistake.  Secondly, I hope you caught the part about the possibility of a HUMAN EMBRYO growing inside of a MOUSE as a result of the MICE REPRODUCING.  Maybe I'm reading too much into this, but that really REALLY FRIGHTENING.  And you have to love the one scientist's reaction to that potential occurrence as basically "not a big deal."
Such chimeras could have useful purposes, though.  For example, it may be possible to use them to produce large volumes of human O-negative blood, which could be used for transfusions in cases of emergency.  Or gamma-globulin, or many other products that we have a hard time getting enough of. 

If there is a disturbing aspect to the prospect of animal-human chimeras, it is this: a fundamental tenet of theological thought is that humans are somehow distinct from other animals.  Humans, they say, were created in the image of God.  They are special, endowed with some degree of divine grace.  Anything that challenges this notion is deeply troubling to those who believe it.  That is why Copernicus and Galileo were so unpopular: the idea that the Earth was not  in the center of the Universe seemed, at the time, to challenge the status of humans as special creatures.  Likewise, the notion that humans descended from nonhumans seems, to some, to debase humanity. 

Intermingling human cells with nonhuman cells may be perceived in the same way.  Some also may hold that it is tampering with God's creation, although why mingling animal cells with God's creation would be worse than mingling dioxin with God's oceans and rivers is not entirely clear.  If all the tampering we already have done has not yet brought God's wrath upon us, using animals to produce life-saving human blood products is not going to do it. 

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
E-mail a link that points to this post:

As the author of one the blog entries you linked to, I'd like to clarify my point since in this context I sound a bit like a raving lunatic.

My main objection is not that humans are somehow distinct from animals. I would find this story equal disturbing if it was a cow embryo growing inside of a mouse. The problem I have is that there are potentially disasterous consequences of these kinds of advances that don't seem to be seriously considered by those doing these experiments.

I think genetic modification of plant seeds is a great example of this. Experimentation went forward to the point that a commercial product was developed and only then was it considered what would happen if the "terminator" seed markers began replicating beyond the fields intended.

In this particular case, what happens if some bizarre human-animal or animal-animal hybrid is formed. What is the status of this creature--can it be destroyed like an animal or does it have rights like a person? I think these are serious ethical/moral questions that have to be considered once these chimera experiments start including human embryos. They should be considered before then, but clearly humans have a much different legal status than a non-human.

I don't deny that there may be benefits to these advances--I'd just like to see some of these longer view considerations being taken seriously by those doing this kind of work.

Andrew Huff
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