Reality Check: After ‘Hunt for Wolverine: Adamantium Agenda’ #4, is X-23 a clone or what?



A confused clone contemplates conception.

In last week’s Hunt for Wolverine: Adamantium Agenda #4, we learned something about Laura Kinney’s origin.  The original X-23 mini-series that introduced her to the Marvel comics universe established her as a clone of Wolverine, carried to term by the scientist Sarah Kinney.

Now, after having a look at Mr. Sinister’s database, which (conveniently) contains the DNA of all mutants, Tony Stark reveals that she is not simply a clone of Logan, but actually carries the DNA of her birth mother, Sarah Kinney, as well.

Image credit: Marvel Comics

That sure sounds like a huge revelation. Does it mean she’s not a clone at all? Can a clone inherit something from its surrogate? What does it mean to clone an animal anyway?

In the real world, scientists have been working on cloning for a while (with admittedly mixed results), but a lot is known about how a mother’s body interacts with the fetus she’s carrying, clone or not.

What little clones are made of

First, it’s helpful to establish a few definitions. According to Google dictionary, a clone is an organism or cell that is produced asexually and is genetically identical to the stock from which it originates. The cells of your body clone themselves all the time as your tissues wear out and are replaced; it’s called cell division. The two daughter cells produced are genetically identical to each other and their mother cell, barring any pesky mutations.

In the case of a whole, separate living organism, cloning gets more interesting.

Scientists have been able to clone a wide array of animals, starting with tadpoles as far back as 1952 (that’s right, cloning is old news), and mammals more recently, Dolly the sheep being the most famous. The first primate clones, macaque monkeys, were just achieved in 2017.

Image from Science News

The most common procedure used for this type of cloning is somatic cell nuclear transfer, in which a nucleus from the cell of an adult or adolescent individual is transferred into a donor egg cell whose own nucleus has been removed.

The egg then continues to develop using the genetic blueprint from the nuclear donor, producing an offspring that is genetically identical to that donor. In this case the fertilized eggs are allowed to develop in a petri dish for a few rounds of cell division and then are implanted in a surrogate to grow to term.

This is ostensibly how X-23 was created. A nucleus from one of Logan’s cells was transferred to a donor cell, allowed to grow for a while, and then implanted into Sarah Kinney. Her genome should therefore be identical to that of Logan’s. But then where could Sarah’s DNA have come from?

Here’s the boring explanation. During pregnancy, some cells are exchanged between mother and fetus. The cells given to the mother can persist for the rest of her life. The number of cells transferred from the mother to the fetus, leading to something called maternal microchimerism, is usually small, and it might function to promote immune system development. Eventually the maternal cells are lost from the individual, or so few remain that they become undetectable.

Stark’s revelation could mean something as huge as Laura not being a clone at all, or he could have just noticed a few lagging cells of Sarah getting in the way, especially if the sample from Laura was taken early in her childhood. But if that’s the case, the sample would have two completely separate genomes, not a trace of Sarah’s DNA within Laura’s own genetic blueprint.

What your momma gave you

There are other ways that a surrogate’s DNA can persist in a clone’s cells, though. While a cell nucleus contains the main load of DNA, the mitochondria carry their own small genome, something only a mother can give you. Evidence suggests that these “powerhouses” of the cells used to be free-living bacteria that were symbiotically absorbed into larger eukaryotic cells.

Because of this maternal inheritance, mitochondrial metabolic diseases are passed along the maternal line. In order for an affected mother to have an unaffected offspring all her mitochondria would have to be replaced.

Or just make a three-parent baby! A fertility clinic in Florida announced in 2016 that they’d taken a nucleus from the egg of a mother with a mitochondrial disease, placed it into the enucleated egg of a donor with healthy mitochondria, and then fertilized the egg with the father’s sperm. In effect this child now carries DNA from its mother, father, and the egg donor!

So could Stark have glimpsed some of Sarah’s mitochondrial DNA in Laura’s data? It’s possible that Sarah was not only the surrogate, but also an egg donor as well, and in that case her DNA really would be running through all of Laura, since all her cells would contain maternally-derived mitochondria.

But there are still other options!

Or didn’t give you?

True chimeras occur when two separate, genetically different embryos are fused together early in development. The resulting adult will carry two sets of DNA without ever knowing about it. There are very few known cases of such events, but they may be more common than we think. Most humans with chimerism have no deleterious symptoms and go undetected.

A famous example of chimerism causing trouble is the case of Lydia Fairchild, who had her children paternity-tested to help enforce child support payments from her former husband, but was stunned when the test results claimed that she was not the mother. Kind of odd, since if a person came out of you, with witnesses around, the fact of the matter tends to go uncontested.

Further examination showed that Fairchild was a chimera, with her ovaries producing eggs containing DNA different than that of her skin cells. A chimeric Laura would be in a similar situation, but again, there would be two separate genomes detected rather than a single, integrated one.

Image credit: Marvel Comics

Getting it right

Maybe Stark’s right and it is the genomic DNA of Laura he saw in the database. When trying to clone Wolverine in the X-23 mini-series, the Y chromosome in Logan’s sample was damaged beyond repair, forcing Sarah Kinney to create a female version. How’d she do that?

Animal studies have had some success in producing sperm cells from somatic cells. If this were the case, Kinney could have used these artificially created sperm to fertilize the eggs she donated. Since the Y chromosome would not be viable, this would produce either X chromosome-carrying sperm or sperm without a sex chromosome, 0.

Women with X0 genotypes have a condition called Turner syndrome, but it would be trivial for Kinney to pluck a cell from the fertilized embryos and genotype it, thereby selecting only the XX embryos to propagate. In this case, she would be the biological mother of Kinney, which would also account for Laura’s physical resemblance to her.

We’ll have to wait a little while to find out what exactly is happening to Laura Kinney, and it will be interesting to see how close to reality the story will stick. In the real world, many of the animals cloned from somatic cells have a shortened life span and the effects seem to be worse depending on how old the donor nucleus is.

But we’re getting closer and closer to the possibility of human cloning, and the scientific community will continue grappling with the ethics of it, something the Weapon X project has never had to worry about.

Yelena Bernadskaya is a developmental biologist specializing in genetics at NYU.

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