Thanks to the many people who left comments on my recent post about some recent work on the intersection of stem cells and human evolution. I noticed that several people expressed variations on the same theme, one which deserves a response. To recap briefly: a great deal of research indicates that a couple million years ago, our hominid ancestors lost the ability to make one of the main sugars that coat mammal cells, called Neu5Gc. This ancient chapter in our history turns out to have a big effect on current research on embryonic stem cells. When human stem cells are raised on a substrate made of mouse cells or calf serum, they absorb the nonhuman Neu5Gc sugars, which ends up on their surface. Humans carry antibodies to Neu5Gc, and these antibodies attack stem cells raised on animal substrates. As a result, existing cell lines fed on this stuff would likely be destroyed if they were implanted in a person.
Some readers questioned whether the research I discussed actually supported evolution and not creationism.
Samuel asked: “If humans are missing this sugar, and the rest of the animal kingdom has it, wouldn’t that make humans unique? Could this evidence also support the creationist theory?”
In a similar vein, Graham Mitchell emailed me, writing, “I do find it interesting that you detail how the loss of this sugar in hominids occurred maybe three million years ago and that most other mammals (including primates) still have the sugar, but yet you interpret this evidence as making Intelligent Design *less* likely. As I was reading along, I thought to myself, ‘Wow, more evidence that a Designer created humans to be distinct from the animals.’”
I’m happy to respond to these messages, but it’s tricky. Neither what Samuel calls “the creationist theory” or what Graham calls “Intelligent Design” offers an explicit hypothesis about how this aspect of our biology came to be. Was mankind created 6,000 years ago without Neu5Gc? Or did a Designer (I’ll use Graham’s capital D) shut down Neu5Gc 2.5 million years ago in hominid ancestors of humans, with the intent of creating a special species? This is the sort of vagueness that leaves practicing biologists cold when it comes to creationism.
The main point Samuel and Graham are making is that the lack of Neu5Gc appears to be the work of a Designer/Creator who made humans unique from animals. But the lack of Neu5Gc does not actually make us unique. Note that in my original post, I did not say that Neu5Gc is found “in the rest of the animal kingdom,” as Samuel put it. I said it was found on every mammal except humans. That’s an important difference. The vast majority of animal species–not mention the millions of species of fungi, plants, and bacteria–do not have Neu5Gc. What’s more, we have a related sugar called Neu5Ac which all mammals do, and which non-mammals orgnaisms do not.
So our lack of Neu5Gc cannot be interpreted as an example of how the Designer made us unique. On the other hand, there’s an obvious (and testable) hypothesis about this evidence that emerges from the theory of evolution. Namely, Neu5Gc and Neu5Ac evolved in the ancestors of living mammals–probably from a similar sugar that can be found on the cells of non-mammals. Then in the human lineage, one of those sugars–Neu5Gc–was lost due to a mutation.
Mind you, evolutionary biologists do not contend that humans are not unique–in the sense that you can scan the human genome and find stretches of DNA not found in any other species. But being unique is not all that…well, not all that unique. A sea slug is also unique, because it also has stretches of DNA not found in any other species. But we would be surprised to hear a sea slug declare that its genetic makeup is evidence that a Designer created it to be distinct from the animals (and not merely because sea slugs are a pretty quiet bunch).
In fact, the study of evolution very much concerned with how humans–and other species–became unique. Evolutionary biologists look at the biology we see around us today and aim to infer how those processes could have produced the diversity of life that surrounds us (and includes us). Some aspects of the history of life are harder than others to study, because there’s less evidence at hand. But in the case of Neu5Gc, some things are nicely clear. The gene that makes Neu5Gc in other mammals is not missing from our genomes. It’s still sitting there. But right in the middle of it is a distinctive sequence of DNA that belongs to a sort that geneticists understand quite well, called an Alu element.
Alu elements get copied by our cells and those copies get inserted all over our genomes. Scientists can watch the process up close by putting molecular tags on Alu elements in a colony of cells, and then watching it spread over time. In the real world, a fertilized egg may wind up with a new Alu element, which then gets spread to every cell in the baby’s body. Out of every 200 births, one child is born with a new Alu element. Sometimes they wind up wedged in the middle of a gene, disrupting its ability to make a protein. In some cases, this leads to a disease. More often, though, the new Alu element ends up somewhere in the genome where it doesn’t do much harm. As a result, Alu elements piled up in the ancestors of living humans. The human genome has 1.2 million Alu elements, making up about 10% of its entire sequence of DNA.
Alu elements all work the same way, and all have the same basic genetic sequence. But they are not identical. That’s because each time an Alu element gets copied, there’s a chance the copying machinery of our cells will make a mistake and introduce a mutation. So Alu elements can be grouped together into families, related by common descent, which in turn can be related to other Alu families. Humans have some unique Alu elements that emerged after we split from other apes, and we also have Alu elements that we inherited from our common ancestor with other apes.
The gene that makes Neu5Gc is interrupted by an Alu element. It’s the same Alu element in the same place in the same gene in every person every studied. Scientists can document Alu elements interrupting genes today, either in laboratory experiments or in the maternity ward.
How do we explain this pattern?
On the one hand, there’s evolution. The basic idea behind evolution is that mutations have continuously emerged in DNA, leading to variations between individuals in a population. Some of these variations may give individuals an edge in reproducing. If those variations can be inherited, they will gradually become more common. Some populations may split off from the other members of their species and become a new species of their own, but they still carry the adaptive mutations from their common ancestors. And over very long periods of time, many mutations can arise leading to new complex traits.
The case of Neu5Gc is completely consistent with evolution. Scientists may not yet understand what advantage the mutation that robbed us of this sugar had, but the fact that our knowledge is incomplete is not a compelling argument against evolution. After all, scientists don’t even know what Neu5Gc andNeu5Ac do today. That doesn’t mean the sugars don’t exist, or that they aren’t important. (As I mentioned before, if you take away these sugars from a mouse through genetic engineering, you end up with a dead mouse.)
Is all of the evidence I’ve presented consistent with “creationist theory” or “Intelligent Design”? Perhaps someone can offer an explanation that can make it fit, but I don’t see it. To create this part of our genome, the Designer would have had to have inserted an Alu element by hand at a particular place in our distant ancestor’s genome in order to produce this change. And if Intelligent Design really is supposed to be a scientific theory, that would mean that every time an Alu element winds up somewhere else in the genome, it’s the work of a Designer. (You can’t just pick and choose the cases that the Designer is responsible for.) And that means that every timesomeone dies of an Alu-related cancer or other disorder, it’s because the Designer invisibly slipped into the body of his or her parents and monkeyed with an egg or a sperm to make sure they died. I look forward to reading the scientific paper documenting that.
Originally published January 28, 2005. Copyright 2005 Carl Zimmer.