Transcript for the Piece Audio version of Ready to be Completely Wrong? Conjectural Genomics.

Reporter: Robert Frederick
The unchanged parts of our genomes are called “ultraconserved elements.” Ting Wu says scientists have no idea why they’ve been conserved, or haven’t changed. Wu is a geneticist at Harvard Medical School.

Speaker: Ting Wu
And here’s the problem: in general computational biology believes is the higher the conservation, the more important the function. So basically what this is saying is the most important parts of our genome — we have no idea about the most important parts of our genome.

Reporter: Robert Frederick
Wu was speaking before a group of science reporters at Massachusetts Institute of Technology. Usually, scientists announce discoveries with lots of reporters around.

Interviewee: Ting Wu
They are, I think some people say, “The most mysterious thing to come from the genome” because they are so puzzling.

Reporter: Robert Frederick
But instead of announcing a discovery, both during her talk and afterward in a one-on-one interview, Wu described what’s considered a more accurate picture of science: not one of discovery, but of trial and error. Lots of error. Literally, she and her colleagues have been trying to prove themselves wrong. And keep failing to do so.

Interviewee: Ting Wu
We were — actually, I have to tell you — stunned every… I thought this model was going to die in two weeks. It’s been 10 years.

Reporter: Robert Frederick
The model — or Wu’s understanding of what just might be the most important part of the human genome — can be described as fairly straightforward.

Interviewee: Ting Wu
I think these elements represent a new kind of genetic element — a new kind of function — and it’s function is simply not to change.

Reporter: Robert Frederick
So, unlike genes that tell what color your eyes are going to be, or allow your body to produce things like insulin, Wu says, really…

Interviewee: Ting Wu
I think the function of these elements is to not change. And I think that it would be just so much fun to have that kind of element.

Reporter: Robert Frederick
What would an unchanging element in a genome be useful for? Wu says you might think of the ultraconserved elements as fences around playgrounds. Inside the playground, the genome can play — evolve, or change. But beyond the fence — outside the playground — no playing allowed.

Speaker: Ting Wu
So they basically keep certain parts of our genome intact while letting other parts of our genome become malleable.

Reporter: Robert Frederick
And let creatures evolve into different things, like birds, snakes, mice, or us. But again, no one really knows yet. As it happens, in one of the many experiments Wu and her colleagues did to try to prove themselves wrong, researchers working in a different lab in California removed the fence: they removed four of the ultraconserved elements from the genomes of mice. In doing so, the researchers thought, if these elements of the genome are so important to have been conserved for hundreds of millions of years, removing them should mean the mice would die, or maybe, if they live, they’ll be unable to have baby mice.

Speaker: Ting Wu
And amazingly these mice were completely viable and fertile. This was a shock, even to us. What it says is that these elements, which have remained unchanged for over 300 million years, or change extremely slowly, they’re actually completely dispensable for viability….

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It’s at this point that I have to tell you I have no idea this model is right. I also need to tell you that it is not a very popular model in the field. The most popular models have to do with ultraconserved elements regulating very important genes. So, this model — for which there, at the time we proposed it, there was no evidence — could explain ultraconservation, but did not fit with what we knew about biology.

Reporter: Robert Frederick
And in the 10 years since Wu and her colleagues proposed their model, what’s changed? Well, scientists have learned a lot more about biology, and Wu has continued to experiment and search for evidence that would make her to say “Oops, we’re on the wrong track.”

Speaker: Ting Wu
In my lab, it’s understood anyone who wants to work on this project, I bring them into my office and we have a conversation and I always tell them that the only way they can work on this project is if they are willing to wake up every morning ready to know that they are completely wrong. And that’s the only way we can go forward. So I could be wrong completely tomorrow.

[music ends]

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