karma chimera

When I was just a wee young thing, my grade school teacher assigned us all reports on a specific animal. I got the duckbilled platypus. Can I just say? I thought my teacher was having me on at first. I mean, come on: it had a bill like a duck, a body like a beaver, and it was venomous like a snake! It could have popped right from the pages of the fantasy stories and ancient myths I devoured so regularly at that tender age. Among other tales, I was fascinated by the myth of the Chimera, a Greek fire-breathing monster described in Homer's Iliad as having a lion's head, goat's body, and serpent's tail, and the platypus seemed eerily similar in concept, if not appearance. But I dutifully did my library research -- this was pre-Internet, so we had to actually look stuff up on paper and use old-fashioned, musty card catalogs and everything -- and sure enough, the animal was very real indeed. I've had a fondness for the platypus ever since. Its very existence made the world seem that much more magical.

My old friend the platypus made for big science news this past week: scientists have just completed the full sequence of the platypus genome. It's a lazy Sunday, and I'm still mulling over all the excellent comments on my last post, so I'll let Juan Nunez-Iglesias, another New Voice from K.C. Cole's science writing class, weigh in with his own thoughts on the matter:

Last year I attended the 2007 conference on Research in Computational Molecular Biology (RECOMB) in Oakland, California. By far the most entertaining talk was given by Jennifer Marshall Graves of the Australian National University in Canberra. Graves talked about the platypus and how weird it is, not just in its appearance, but in its genetics.

For example, one of the first principles of genetics is that of independent assortment of chromosomes. We have two full copies of our genome in every cell in our bodies: one from our father, and one from our mother. Each copy consists of 23 chromosomes, separate pieces of DNA. When a germ cell divides, it splits our own double-copy genome in two and places each half into one daughter cell -- to pass on half of our genome (per offspring) to the next generation. The principle of independent assortment states that each of our 23 chromosomes has a 50% chance of ending up in one or the other daughter cell, independent of where the other 22 end up.

This principle was first formulated by Gregor Mendel in the 19th century, and has been shown to hold for every organism ever tested -- save the platypus. The platypus has 5 sex-determining chromosomes from each parent, and all its sex chromosomes stay together generation after generation. A platypus's young will inherit all the sex chromosomes from that platypus's father or from its mother. But never a mix of the two, as happens with all the other chromosomes.

Well, the weirdness doesn't stop there. Researchers announced [last week] the release of the complete sequence of the platypus genome, publicly available online. [Jen-Luc Piquant notes that this would be a fine time to create your own cloned pet platypus, boys and girls!] Down at the single-base pair level, the platypus continues to be weird. Half of its genome looks like a reptile's, half like a mammal's. It also has genes to make venom, which not surprise you after hearing the reptile thing, but... surprise! The platypus venom genes evolved independently of the reptile ones; they are completely unrelated and unique. You can read all this and much more in this excellent article in Nature News. Definitely an exciting time to study genomics.

That sounds suspiciously like a chimera-like creature at the genetic level, doesn't it? Except it isn't. Let me just say that right up front before PZ Myers gets all medieval on my ass. Seriously, PZ's frustration with the media coverage of our friend the platypus inspired him to write this terrific post explaining why the platypus is not the the same as a chimera:

"Over and over again, the newspaper lead is that the platypus is 'weird' or 'odd' or worse, they imply that the animal is a chimera.... No, no, no, a thousand times, no; this is the the wrong message.... What's interesting about the platypus is that it belongs to a lineage that separated from ours approximately 166 million years ago, deep in the Mesozoic, and it has independently lost different elements of our last common ancestor, and by comparing bits, we can get a clearer picture of what the Jurassic mammals were like, and what we contemporary mammals have gained and lost genetically over the course of evolution."

Got that? The platypus is not a chimera. Take it from someone who really knows this stuff. Okay, but do chimeras really exist? I'm so glad you asked. Certainly the mythological Greek monster isn't real, but there is a genetic anomaly that gives rise to a rare condition known as chimerism. Per Wikipedia, "A chimera is an animal that has two or more different populations of genetically distinct cells that originated in different zygotes." (Genetically distinct cells originating from the same zygote produce a related condition called mosaicism.) In humans, it's long been believed to be an exceedingly rare condition, with fewer than 40 reported cases.

One of the most famous is Lydia Fairchild, the subject of a documentary called The Twin Inside Me. She separated from her husband while pregnant with her third child, and took a DNA test to prove her husband's paternity, as required to qualify for welfare support. He was, indeed, the father, but according to the test, she wasn't the children's mother. She was taken to court for fraud. She was only exonerated when she gave birth to her third child, with a judge-ordered witness present to take blood samples from mother and infant for testing. And those DNA tests revealed she wasn't the mother of that child either. Except she was. I mean, court-appointed eye witnesses watched her give birth. If she was a fraud, she was a damned good one, on a par with the world's best illusionists. 

A similar thing happened (without the charges of fraud) to Karen Keegan in 1998, a Boston-area teacher who needed a kidney transplant. She had three grown sons who were tested to see if they could be donors, but the DNA showed that two of them weren't her biological children. This time doctors did additional testing on Keegan, drawing samples from other areas of the body, and discovered she had two sets of cell lines with two separate sets of chromosomes -- a mix of two individuals, fraternal twin sisters who fused in the womb and developed into a single infant. Fairchild's lawyers heard about the case, and arranged for their client to undergo more testing as well. She, too, turned out to be a chimera. For instance, the DNA in Fairchild's skin and hair didn't match that of her children, but the DNA from her cervix did.

Now that's weird -- weird enough to inspire episodes of both House and C.S.I. In "Cane and Abel," House treats a young boy who suffers from seizures and believes he was abducted by aliens; the hallucinations turn out to be caused by the "alien" brain tissue from the twin brother who had merged with the boy in the womb. The C.S.I. episode ("Bloodlines") involved a rape victim who correctly identifies her attacker, only to have him exonerated by DNA evidence, although it demonstrated her rapist was related to the original suspect, who had many brothers -- none of whom proved to be a positive match. The suspect turns out to be a chimera: two different sets of DNA. Grissom discovers the suspect's unique condition when he notices visible Blaschko's lines while photographing said suspect's torso for evidence.

Bizarre though it sounds, according to this 2003 article in New Scientist, chimerism might not be as rare as previously believed; in fact, some researchers are beginning to think there might be a little bit of the chimera in all of us. Most cases simply aren't detected. Usually, there aren't many outward signs or symptoms: eyes of slightly different coloration, for example, hair growing differently on opposite sides of the body, even hermaphroditism (having both male and female genitalia -- the subject of another memorable House episode in which a beautiful young female model turned out to have testicular cancer). Male tortoiseshell tabbies are examples of chimerism. It takes a DNA test to reveal the chimerism, and usually more than one, with samples taken from different parts of the body.

A more common variant is blood chimerism, when fraternal twins share part of the same placenta and exchange blood, which settles in the bone marrow, so each twin is genetically separate -- except for their blood which has two distinct sets of genes and two distinct blood times. Some 8% of fraternal twins are blood chimerism, and the number could rise given the increase in multiple births, thanks to in vitro fertilization. Fairchild and Keegan are much rarer cases.

Of course, it was only a matter of time before scientists started creating chimeras in the lab -- yes, just like the infamous South Park episode where the local mad scientist created creatures with multiple derrieres. Okay, not like that, but in 1984 scientist combined a embryos from a goat and sheep to form a "geep." Others have made rat/mouse and rabbit/human chimeras (2003), as well as pigs with human blood flowing through their bodies. Most were created not with the intention of creating living hybrids, but for the purpose of harvesting stem cells for further research. And in 2007, scientists at the University of Nevada's School of Medicine created a sheep with 15% human cells. In the UK, researchers are attempting to insert human DNA into a cow's egg using the same technique that successfully cloned Dolly the Sheep. Last I heard, they hadn't yet succeeded.

Sheesh. Truth really is stranger than fiction sometimes. A creature from Greek mythology has a counterpart in modern 21st genetics. Next scientists will be telling us that vampires and werewolves are real. Which means we might be in need of a Slayer or two. Any takers?

Comments

[Oskar]

Discoveries like this always reminds me of that great line from Hamlet: "There are more wondrous things between heaven and earth, Horatio, than are dreamt of in your philosophy" (I've taken a slight liberty with the quote and replaced "to" with "between" and added "wondrous". The quote works much better this way as a slogan for science. Apologies to Shakespeare). Stranger than fiction, indeed.

I don't know if you've listened to the recent Radio Lab episode "(So-Called) Life" (which can be found here: http://www.wnyc.org/shows/radiolab/episodes/2008/03/14 ), but it discusses these things in some depth, it includes an interview with the Chimera-woman and a discussion of geeps. Any person who is even mildly interested in science should really subscribe, it's one of the most well-produced, informative, interesting, funny and philosophical radio shows of all time (the episode on morality will knock your socks off, then again, most of them will).

It's staggering to think that while the rest of us mammals and reptiles have gone on and evolved our asses of, all along, there have been the lonely platypus, doing it's own thing, evolving at it's own pace, and now with modern genetics we can look at the platypus and find out about our own ancestry. I can't understand people who don't buy into evolution, look at the wonderful discoveries that they're missing out on! We're learning about what we looked like, hundreds of millions of years ago! Talk about heritage!

(PS. You snuck in a little Buffy-note at the end (I love it when you do that!), so I thought I'd add another: remember Adam? Now HE was a chimera! And remember how they defeated him? With the whole mixing together of the essences? Never really understood what Xander added to the mix, but it's always nice when he gets to contribute to the ass-kicking)

[Ed Yong]

Great article, Jennifer. To add to your tour de force on chimerism, I just wanted to big up a PNAS study from last year, which showed that chimerism is pretty much par for the course for marmosets. Because marmoset twins exchange cells as embryos, the adults can carry tissues that are identical to those of their siblings. Including sperm. Which means that marmoset males can fertilise females with the sperms of their brothers, and marmoset babies can inherit genes from their uncles as well as their parents. I've blogged about this here: http://tinyurl.com/62zt2f

[Ville]

Really fascinating stuff. Makes me wonder what kind of quirky situations will arise in the not-*that*-distant future when DNA testing is affordable and common.

[Danniel]

About the platypus, even though it's not a chimera in the other biological sense of fused embryos, I think it's not inappropriate to describe it as an evolutionary chimera as well. But yet much of the coverage on the subject was indeed disgusting, but not because of the eventual use of the word "chimera" itself, but because of the false aura of oddness and strangeness they've created and poor clarification on what it really means. Evolutionary intermediate forms between separated branches are in a certain way, chimeric organisms, they often share traits of the groups that descended from it later, which, by current "standards", look unique to only one of the branches. That's what defines a chimera, isn't it? But the media coverage really made a mess. Platypus happens to be somewhat more prone to confusion, than say, Archaeopteryx, which is a "chimera" that mixtures reptiles and birds, as it has that convergent "duck bill" --which is as biologically related to the duck's bill as a dog's snout anyway-- and to add to that confusion they mentioned that it also has "bird genes" in a way that almost lead to the idea that it would have been either the product of divine creation/humor or of a ménage à trois between animals of different taxonomic classes. Once I heard in a podcast or something, that Matt Ridley's instructions for writing about science in The Economist were "to simplify and then exaggerate"; I think that can be the recipe for disaster.

[Stephanie]

A fantastic bit on chimeras, focusing on Karen Keegan (you get to hear her tell her story) is on WNYC's Radio Lab podcast (which you should listen to if you haven't, it's by far the best science podcast out there) at http://blogs.wnyc.org/radiolab/2008/04/08/so-called-life/.

Stephanie
http://sciencegeekgirl.wordpress.com/

[MyA]

I believe the second reference to a House episode is incorrect. If we're talking about the same pretty young model with testicular cancer, she was not a hermaphrodite. She did not have any sort of ovary or uterus. She had AIS (Androgen Insensitivity Syndrome, I believe); her body turned testosterone into estrogen, so although her DNA was male, her body was female. As far as I know, AIS is not caused by chimerism, and a person with AIS would have consistently male DNA. However, AIS is still fascinating.