If Aneuploidies = Sexes, Then Two-Headed Turtles Aren’t Turtles

It should've been an easy question.

Some biological questions are pretty straightforward, although people can make them unbelievably complicated. One example is the question of how many human sexes there are (not genders, that’s a different question).

There are two ways that a simple question gets complicated.

The first is when someone researches a topic and learns a lot of facts, but doesn’t have the intellectual background necessary to understand the information or appreciate the nuances. We all know people like that. They’re like Cliff Clavin in the TV show, “Cheers.”

The second way is when people confuse questions about language with questions about reality. For instance, if you think that a sack of potatoes is a chair because you can sit on it, and I disagree, there’s no point arguing about the molecular structure of chairs. We’re using the word “chair” differently. Full stop.

In my opinion, the best way to think through complicated questions is by using analogies. For instance, when I teach about brain function, I draw analogies to computers. This gives my students a way to think about the neurological complexities from a different perspective and (hopefully) view them through fresh eyes.

Given the current difficulty in defining the terms “male” and “female,” I wanted to rethink the question from a couple of different perspectives. As always, I’m not claiming to be the ultimate authority, but I think that I have a point of view worth considering.

Part One - My best friend, Billy

Billy was my very best friend in middle school. We spent our time together catching frogs, doing science experiments in the garage, and collecting bugs. We were inseparable for a couple of years until his family moved away. I missed the guy.

Oh, and Billy was born with only one arm.

Part Two - Heads Up

Biology seems fickle and uncaring. Any adult with a full-length mirror knows that.  None of us are the Platonic ideal of a human, and each of us falls short of what we think we should be.

Our shortcomings notwithstanding, most of us are keen enough to know the difference between human development when it goes as expected, and what can happen when it veers off course as it did for Billy. We recognize those developmental detours as biological anomalies, or deviations from the (statistically) common norm.

Of course, our anomalies – and we all have some — don’t make us less of a human, or a less valuable person. Nor do they make us less deserving of love, respect, or social standing. They are simply unique threads in the human tapestry.

We also know that our anomalies don’t define us as different “types” of human beings. Billy and I were of the same ilk, rambunctious young boys. Our physical differences were simply variations on a theme. They didn’t redefine the theme.

Let me use an example that doesn’t hit so close to home.

About 650 million years ago, several groups of animals evolved heads. Before this, animals didn’t have heads. Think of sponges and jellyfish.

Animals that evolved heads grew just one. So, for over half a billion years, millions of vertebrate animals like fish, amphibians, reptiles and mammals have been characterized as having just one head. Ask any biologist how many heads a vertebrate has. She’ll look at you funny, and reply, “One… and that’s a silly question.”

“But wait,” you might say, “I know for a fact that sometimes animals actually grow two — and occasionally three — heads. I’ve seen it in fish, snakes, turtles, and mammals, even people.”

“That’s true,” she’d say. “It’s also true that sometimes an animal is born with an undeveloped head and no brain. That’s called anencephaly. But, just like having more than one head, these are biological anomalies. They don’t redefine what it means to be a snake, or a turtle, or a human. As a biologist, I can recognize a turtle as a turtle, and still be aware of the fact that some turtles are a bit different than others. I certainly wouldn’t say that turtles have a spectrum of heads from zero to three, or that a two-headed turtle isn’t a real turtle. The answer to your question is still one head.”

But, you’re insistent. You’ve been doing Internet research. You press on.

“How about if I take an animal to a research clinic and have them surgically add a second head? I know that’s been done with salamanders, rats, dogs, even monkeys. And, the extra heads do OK for a while. They’re even talking about doing head transplants on people… Doesn’t that mean that animals or people can have a spectrum of heads? Maybe these are even new types of animals.”

“No!” she’d tell you. “Biological anomalies or surgical modifications don’t change the fact that vertebrates — from fish to humans — are characterized by having just one head. You can’t change that. A two- or three-headed turtle isn’t a new kind of turtle or an ‘intermediate’ turtle. It’s just a turtle with a developmental anomaly. Likewise, a monkey with a second, surgically attached head is still a one-headed monkey with an extra head attached. Get it?”

Hopefully, you’d reply, “Yeah. Got it!”

Part Three - Anomalous Aneuploidies

Arguably, the most important — and one of the more complicated — biological tasks that you have to accomplish is producing gametes, sperms or eggs.

Each gamete is a unique, one-celled organism whose job it is to deliver exactly 50% of your chromosomes to another gamete that’s carrying a matched set. The difficult part is packaging exactly the correct 50% into the gamete. It's difficult because sperms and eggs develop from cells that contain 100% of your chromosomes, twice the number needed. You’d think that the easiest way to make a gamete would be for the original cell to divide in half. But nothing in biology is easy.

Instead, just before the original cell divides, it duplicates all of its chromosomes. So, it begins with four times as many chromosomes as the gamete needs. To reduce that number to 50%, the cell has to go through two rounds of division. (Does the math make sense?)

The tricky part is that before each division, the chromosomes have to line up in a double row of matched sets in the middle of the cell. Then, strands of proteins pull each row in opposite directions and the cell divides into two. This has to happen twice. The second division creates the cells (gametes) with 50% of the original number of chromosomes.

Producing gametes requires choreographing dozens of biological processes. Most of the time, all goes well. However, sometimes the chromosomes don’t separate properly. This creates an egg or sperm with too few, or too many chromosomes. This anomaly is called an aneuploidy (AN-yoo-PLOY-dee).

You’ll recognize that just like my friend Billy isn’t a different kind of human, and a two-headed turtle isn’t a different kind of turtle, an aneuploid gamete isn’t a different kind of gamete. It’s still either an egg or a sperm but with a biological anomaly.

If an aneuploid sperm fuses with a normal egg (or vice versa), the fertilized cell is going to have the wrong number of chromosomes. When the fertilized cell divides into two daughter cells, and those cells divide, and so on, the error gets repeated with each division. Consequently, the developing animal — or person — will have the wrong number of chromosomes in its cells.

Probably, the best-known human aneuploidy is Down syndrome in which a person has an extra 21st chromosome. However, there are many more examples, some caused by an addition or deletion of one, or just a portion of one chromosome. Most aneuploidies are severely debilitating or fatal. However, under no circumstances would we consider these individuals different or intermediate types of humans. They are all people deserving of the same respect and moral status as any other person.

In contrast to aneuploidies like Down syndrome which is caused by a somatic (non-sex) chromosome aneuploidy, there are aneuploidies caused by too few, or too many sex chromosomes. This is where the current confusion occurs.

In the vast majority of cases (over 99.5%), a human has two sex chromosomes, XX or XY. However, although rare, a person can end up with just one X, or a combination of multiple X’s and Y’s, for instance: X, XXY, XXX, XXXY, XXYY, XXXXX.

Some people mistakenly think that these aneuploidies are equivalent to different sexes or different points along a continuum of sexes. However, based on what we’ve discussed so far, that’s not really accurate, is it? These anomalies don’t create unique types of humans or unique sexes. Nor do they redefine the basic categories in terms of which we understand sex. In fact, these kinds of biological anomalies can be understood only in terms of the biological standards from which they diverge.

You can read any number of articles on this controversy. Some are quite good. Others are confused, unnecessarily detailed, and pretty boring. I guess that some people think the answer is hidden somewhere in the details of molecular biology. However, it never is.

In truth, this controversy is really about language, not biology. Biologists can recognize the fact that there are two distinct human sexes and still understand that there are anomalous edge cases. (Both biology and language are like that.)

So, let me ask you. In your opinion, is a person with four X chromosomes a unique sex, or a female with a biological anomaly? Is a person with three X’s and a Y chromosome a unique sex, or a male with a biological anomaly?

Is a two-headed turtle a new intermediate type of turtle, or just a turtle with a biological anomaly?

Was Billy just a regular guy who happened to be my best friend, or an intermediate type of human?

I think the answers to all of these questions should be similar... but, it’s your call.