[♪ INTRO] There’s a saying that there are two things in life that you’re never truly prepared for: twins.

And that is in large part because twinning is somewhat rare in our species. Only about three percent of live births involve multiple fetuses.

Most of these are dizygotic, or what’s commonly called fraternal twins. They occur when a person just so happens to release two eggs instead of one, both of which get fertilized and successfully implant. A smaller percentage of twins are monozygotic or “identical” twins.

Those are the twins that share essentially all of their DNA because they come from a single fertilized egg which later split into two. And both of these types of twins are useful for scientific studies because they can help us sort out the influences of genetics and environmental factors on different traits. But it turns out that twinning is a lot more complicated than just identical or fraternal.

And the rarer types of twins suggest that we have a lot more to learn about human development. The name “mirror image twins” basically says it all. They’re a type of monozygotic twin where the two people are physical mirror images of each other.

Like, if one twin is right-handed, the other might be left-handed. The mirror twin’s internal organs might even be on the opposite side; what physicians call situs inversus. So while that degree of mirroring only occurs in about one in every 10,000 people, some degree of mirroring in identical twins is pretty common.

Some scientists think this is a hint as to when the twins’ embryo actually split. You see, within the first couple of weeks of embryonic development, the cells that will eventually give rise to organs become programmed for the right or left side of the body, a process called left-right asymmetry. During this window, left and right are determined, but the embryonic cells haven’t yet migrated to the positions where they will ultimately grow into body parts.

So it’s thought that full mirror image twins only occur when a single embryo splits after this has happened; sometime around two weeks after fertilization. But there is some debate about this. So, the concept of “identical” twins isn’t really true; there are always some slight genetic differences between twins.

So it’s possible that those genetic variations might actually explain mirroring better than when the embryo split. And even if it is a timing thing, the research isn’t clear on exactly when splitting will result in mirrored traits like hair whorls or handedness, as opposed to full blown asymmetry of organs. And that’s because we can’t actually see a human embryo splitting in utero.

Ultrasound technology is good, but it is not that good. Though, even if we could see twinning happen, we’d probably miss it for most pregnancies, since it happens during the earliest stages when a person might not even know that they’re pregnant. Still, whether it’s about when the split happens, or genetic differences between twins, or something else, piecing together the mechanism behind mirroring has the potential to teach us a lot about how our developing bodies determine where our different pieces go.

You’re probably already familiar with conjoined twins; twins that remain at least somewhat attached at birth. For better or worse, they’ve received a lot of attention both medically and culturally. Still, we’re not sure how conjoining happens.

And examining cases more closely has kind of upended everything we thought we knew about twinning. The earliest and still common explanation for conjoinment is that it’s a result of incomplete splitting; what’s often called the fission theory. This is actually how all monozygotic twins supposedly happen: for whatever reason, one embryo splits into two.

And, so the theory goes, if this happens super early, both twins develop their own amniotic sacs and their own placentas. If it happens a little later, they share one or both of those. And if the split is really late, like, two or more weeks into development then you get conjoined twins.

It’s thought that, for some reason, splits that occur that late fail to fully separate. And that makes a lot of sense intuitively, and there are other reasons to think that conjoinment has to do with late embryo splitting; like, that there are higher rates of mirroring in conjoined twins. But, remember, mirroring might not be a timing thing after all.

And many researchers think conjoined twins don’t arise from incomplete splitting. Their model, dubbed the fusion theory, posits that the embryo does completely split, and this split occurs a lot earlier on. But then, as the two twins develop, they end up physically colliding and they grow back together.

This might explain why most cases of conjoined twins are joined at the chest and often share a heart. See, early on in development, the primordial heart is one of the few parts of the body that isn’t covered in the type of cells that will become skin. That may mean that that area is more vulnerable to rejoining.

Sorting out which of these two theories is right, or if they both are, at times, would help scientists better understand how and when cells become programmed into different tissues and why twins happen in the first place. About ten percent of conjoined twins are considered external heteropagus twins. Essentially, one twin doesn’t develop all of their organs or body parts, so they rely on the other twin for survival.

This undeveloped or asymmetrical twin may even look more like a mutation than a separate, attached entity. Like, a while back there was a viral video of a pretty cute puppy with a tail that was sticking out of its head? That was probably an external heteropagus twin.

Much like other conjoined twins, it’s long been assumed that such twins arise when an embryo splits late in the game and doesn’t split perfectly. And for some reason, the split is also fairly lopsided, so one twin either doesn’t develop well enough to survive, or is essentially part of a person attached to their twin. That kind of wonky fission could explain how you’d end up with a tail sticking out of a puppy’s head.

But similar cases in people may actually support the fusion theory instead. See, here’s the thing: no one has ever seen fission happen. We have never witnessed a human embryo split in two, even though techniques like IVF can involve culturing embryos for almost a week.

That means that we’ve never really confirmed the idea that the timing of embryo splitting makes any difference, and we don’t actually know that an embryo can split partially or unevenly and still survive. But we have come pretty darn close to definitive evidence of fusion, thanks to a heteropagus twin case published in 1997. The child described in the study was born with what appeared to be a pair of legs growing out of his chest.

But they weren’t his. Genetic tests suggest that the legs were from a fraternal twin. Which, if true, means that two distinct embryos fused at some point.

Of course, that’s just one case. But it does suggest that further research on this kind of twin could help settle the fission/fusion debate, or determine that both of them can happen. Either way, it would provide researchers with greater insights into how developing human cells behave, which could in turn help doctors treat cases where development doesn’t go as planned.

Sometimes, a heteropagus twin can exist wholly inside its healthy twin, as a fetus in fetu. Okay, I say sometimes, but let’s be clear that this is really rare: less than two hundred reported cases have ever been reported. And usually, there’s just one, but there is a case report of eleven fetuses in fetu!

Not only is there some debate about how fetuses in fetu happen, some researchers don’t think it’s a twin at all. They believe that a fetus in fetu is actually a highly developed teratoma; a kind of tumor made up of several body tissue types. There are also some that think it stems from a kind of error during development where some stem cells that can become anything divide weirdly.

But others say it has to be a true twin, because fetuses in fetu have vertebral columns, and often, other developed body parts like limbs. And of course, everybody here could be right, there could just be lots of different ways to end up with one partially-developed fetus inside of another. That would mean studying fetuses in fetu could help doctors understand why some fetal tumors become problematic while others stay benign.

And it could teach us some really cool things about developmental programming. Plus, it could give us further insights into twinning. See, it could be that fetuses in fetu happen because one twin envelops the other at some point.

So, kind of like the fusion idea, but all the way. And that actually isn’t as far-fetched as it might sound, because there are cases where one twin absorbs part of or all of the other. Now, you may have heard that you could be your own twin without even knowing it.

That’s based on a phenomenon called vanishing twin syndrome, where, very early on in a multiple pregnancy, one of the twins just kind of disappears. Except, it doesn’t really. Doctors now think that vanishing twin syndrome occurs because, when one twin dies spontaneously, it is generally absorbed by the other twin.

And by absorbed, I don't mean the tissues are broken down for molecular parts and digested or something. No; whole, living cells get incorporated into the twin's body So one baby is born, and that baby has two people’s genomes, making them what biologists call a chimera. And it turns out this kind of merging of cells doesn’t just happen when a twin dies.

It’s also how you end up with chimeric twins: dizygotic twins where one or both has cells with the other twin’s genome. Fetal cell swapping might occur in monozygotic twins, too, but since they have essentially the same genome, it’s not really notable. When twins are dizygotic, though, the other twin’s cells stand out.

And researchers have found clear cases of this, like, twins which have two distinct blood cell lines. So some of their red blood cells are type A while others are type O. What’s amazing is that this kind of blood chimerism seems to occur in about 8% of dizygotic twins; 21 % of triplets!

And the other twin’s cells can end up basically anywhere in the body. In one case, a man fathered a child that had his twin’s DNA! This episode continues to blow my mind!

And there’s also a lot we can learn from these multi-genomed twins. Doctors don’t fully understand how the cells make their way from one twin to the other, why they do it, or what it means for either twin. It’s also not clear how these twins’ immune systems handle having cells with different genomes.

Understanding that could teach us a lot about our immune systems in general. Plus, on a practical level, research into chimeric twins could help doctors predict and manage compatibility issues that might arise during blood transfusions or organ transplants. Last but not least is the rarest type of twin.

So far, we have talked about subsets of either monozygotic or dizygotic twins. But sesquizygotic twins are also a thing, though there have only been two reported cases. These are twins that share between 50 and 100% of their DNA.

So they are more genetically similar than dizygotic twins, but not quite as similar as monozygotic twins. And no one is really sure how sesquizygotic twins happen, but biologists have a couple ideas. One is that a single egg becomes fertilized by two separate sperm, a phenomenon called dispermic fertilization.

If such an egg were to split so that each half ends up with, more or less, a single, complete genome, that could result in what scientists refer to as semi-identical twins. What’s not clear is how the dually-fertilized egg actually does that. Because generally, dispermic fertilization results in one embryo with an extra set of chromosomes; a condition which is fatal.

So another hypothesis for sesquizygotic twinning is that it arises from the fertilization of a polar body. Polar bodies are small, immature cells generated by the cell divisions that occur during egg development. They usually die or disintegrate once the egg matures.

But if a polar body were to be fertilized around the same time as its associated mature egg cell and both developed, you could hypothetically end up with what’s generally called half-identical twins. It is not clear how a polar body could become fertilized, though, let alone develop into an embryo. Not even all mature eggs succeed at that.

So understanding the mechanism, or mechanisms, of sesquizygotic twinning could help us better understand what is and isn’t required for fertilization and embryonic development. And it could hint at new ways to help people who want to become pregnant successfully do so. There you have it!

Twinning is way more complicated than identical or fraternal. These rarer types of twins, from fetuses inside of fetuses to living mirror images, can teach us a lot about what actually happens during human development, and lots of other things. So when we finally do figure all of this out, the knowledge will likely benefit everyone.

Thanks for watching this episode of SciShow! And thanks to today’s President of Space, SR Foxley. SR is one of our patrons on Patreon, so he is part of the wonderful community that supports SciShow and loves learning together.

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