Archealization by CRISPR

Credit Muotri Lab/UC San Diego

Alysson Muotri is a neuroscientist at the University of California, San Diego. His team is developing lentil-size, Neanderthalized mini-brains by using CRISPR + paleogenomics + organoids. After reading the paper published in Science last February, we asked him a few questions about the experiments of paleo-gene-editing he is doing at the Archealization Center.

1) First of all, what does the word archealization mean?

It is a made-up word, we created it because we have a new concept that did not exist before, it means to go back to the archaic format.

2) In your lab neurons go back to the Neanderthal stage one gene at a time. Let’s imagine that you can edit all in once the 61 genes for which the sapiens version is consistently different from that in archaic human types.

If you are trying to replicate the Neanderthal brain, the more the better, and most likely the combinations of the 61 genes will be more informative. Still, there are thousands of non-coding variants to incorporate. But my goal is different, I want to sort out what are the evolutionary steps that made the modern human brain. So, to do this, we have to first test one by one. What we are actually doing is re-playing the evolution of the human lineage in a dish. We are just using Neanderthal genomes to find the target genes.

3) I like to think that Neanderthals and us are different human types, not different species. Do you consider this issue relevant to your work?

I agree with you, they are a different human type. But it is irrelevant for my research.

4) When do you expect organoids will be ready to join DNA, bones, and artifacts to unveil the evolution of human cognition?

I think this work is a nice step forward in this direction. Having a list of genes is not enough to understand evolution, we need to test them in relevant models.

5) Several years ago, the gene FOXP2 seemed to be the candidate to answer the question of what it means to be human. Now the focus is on NOVA1. But even if we could understand the function of every mutation that we have and Neanderthals do not, don’t you think the findings would be so complicated that few people will find the answer comprehensible and emotionally satisfying?

Please note that the FOXP2 gene is identical between modern humans and Neanderthals. It is not in our list of 61 genes. It could be that the answers will not be comprehensive, but maybe not. I am always in favor of doing the experiments first, before you conclude anything. Otherwise, these are just opinions.

6) In its book about what makes us human, Michael Gazzaniga says he asked many thinkers and got a collection of answers. For example, a teacher suggested we are the only animal to actively teach their young. An accountant mentioned mathematical abilities. A five years old said that animals don’t have birthday parties. What about you?

I personally think that there are not many things that are uniquely human. I think animals do most of what we do: they teach their young, they do have mathematical abilities and they might well celebrate birthdays. To me, to be human is more related to the “intensity” of certain abilities, rather than have it or not. I often use technology, arts, and adaptation as examples. We see this in other animals, but not with the same intensity. Other animals (including what we know from the fossil records of our extinct relatives) are not trying to go to Mars or creating arts as we do. Thus, in that sense, we are outliers in evolution.

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