Mighty Mice Return From Space : Short Wave Some very unusual mice with big muscles are back on Earth after a month on the International Space Station. NPR science correspondent Jon Hamilton shares the story of the two researchers behind the experiment. What they learn could help people with disabling bone and muscle diseases and another group with muscle problems, astronauts. Follow host Maddie Sofia on Twitter @maddie_sofia. Email the show at shortwave@npr.org.
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Mighty Mice Return From Space

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Mighty Mice Return From Space

Mighty Mice Return From Space

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MADDIE SOFIA, HOST:

You're listening to SHORT WAVE from NPR.

(SOUNDBITE OF MUSIC)

SOFIA: Maddie Sofia here with NPR science correspondent Jon Hamilton. Or do you prefer J. Ham? J.J. Hammer?

JON HAMILTON, BYLINE: (Laughter) I'll be whoever you want me to be, Maddie.

SOFIA: (Laughter) So you are here to talk to us about big muscles.

HAMILTON: Right. I've been working out and - just kidding. These are big muscles attached to mice.

SOFIA: Like, we talking Mighty Mouse...

(SOUNDBITE OF SONG, "MIGHTY MOUSE: THE NEW ADVENTURES THEME SONG")

UNIDENTIFIED SINGERS: (Singing) Zoom, zoom. Boom, boom, boom...

SOFIA: ...The little Mighty Mouse guy?

(SOUNDBITE OF SONG, "MIGHTY MOUSE: THE NEW ADVENTURES THEME SONG")

JONATHAN SEGAL: (Singing) Here he comes that Mighty Mouse, coming to...

HAMILTON: Right. Like Mighty Mouse, except these mice got all bulked up after scientists modified their genes.

SOFIA: Why are we giving mice bigger muscles, Jon?

HAMILTON: Actually, there is a serious issue here. The way scientists were able to increase the muscle mass in mice - it could ultimately lead to new treatments for people with diseases that cause muscles to waste away - you know, so diseases like muscular dystrophy.

SOFIA: All right, I'm on board with that. Go on.

HAMILTON: And these mighty mice have something else in common with the superhero mouse. They have also been to space.

SOFIA: (Laughter) These are busy mice, Jon.

HAMILTON: They are. And some of our mighty mice were just on the International Space Station. They got back just a couple of weeks ago. And they were up there as part of this experiment that could help save the day for another group of people who have muscle problems. And I'm talking here about astronauts.

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SOFIA: So today on the show, how these mice got their muscles and what it could mean for treating certain diseases.

HAMILTON: Plus, why the mighty mice went to space, and the husband and wife team - both scientists - who were behind it. It's the combination of decades of research.

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SOFIA: OK, Jon, where should we start?

HAMILTON: Well, let's start with a guy named Se-Jin Lee. I should say Dr. Se-Jin Lee. I visited his lab back in 2006, and this was when he was at Johns Hopkins Medical School in Baltimore. And that is when I got to meet my first mighty mouse.

SE-JIN LEE: This was one that I've actually engineered, has about four times the muscle mass of normal mice.

SOFIA: Four times. So what do they look like, Jon?

HAMILTON: Totally jacked. It was, like, meeting this mouse version of Arnold Schwarzenegger, you know, back in his Mr. Universe days. And Se-Jin told me that what you can see on the outside of these mice is nothing compared to what's underneath all that fur and skin.

LEE: If you open up the mouse and actually look at the muscles, it is just really unbelievable.

HAMILTON: But even just looking at him here, he's got huge - I don't know what muscle that is, quadriceps, bicep...

LEE: Yeah, down here. Yeah, so down here, that's the quadricep...

HAMILTON: I mean, his shoulders are incredibly bulky.

LEE: These animals are almost getting to the point where they don't really look like mice. You know, they just have a different look to them.

SOFIA: That's wild. Like, there - I have seen them, and they are yoked. They're big mice.

HAMILTON: Oh, yeah.

SOFIA: So how did they genetically engineer this mouse to give it bigger muscles?

HAMILTON: Well, Se-Jin and this team of scientists discovered this protein that is produced by muscle cells. This is back in the late 1990s. And what they found is that in a developing embryo, this protein's job is to limit the number of muscle fibers that are formed, right? Then later in life, the same protein limits the growth of those muscle fibers to prevent your muscles from getting too big. And that protein is made by a specific gene. So if you create a mouse without that gene...

SOFIA: Then you don't have the protein that limits muscle growth, so you get a big, ol' mighty mouse.

HAMILTON: Exactly. And the team named the protein myostatin.

SOFIA: OK, got it. So what does that mean for humans?

HAMILTON: Well, back when the mighty mice first made headlines - it was back in 1997 - the humans who were most interested were bodybuilders.

SOFIA: OK.

HAMILTON: And Se-Jin told me his lab's phone started ringing almost immediately. Emails started pouring in. And everybody wanted to get some of what mighty mouse was taking, right? And, of course, after this discovery, there was huge concern that drugs that tweak myostatin could become a big problem in sports.

SOFIA: Right. But these mice were genetically engineered, right? A person just can't take a pill to make this happen.

HAMILTON: Well, not yet. But you know, ever since myostatin was discovered, drug companies have been working on products that can reduce myostatin. And there have been several drugs that were even tested in humans. The companies still haven't really quite figured out how to duplicate the results in mice. But if they do and one gets FDA approval, it could help tens of thousands of patients who have genetic diseases, like muscular dystrophy. Or it could help many more people with muscle wasting associated with cancer or with kidney disease or even old age.

SOFIA: So let's talk about how all this is connected to astronauts and sending these mice up into space.

HAMILTON: To explain that, I need to introduce you to Dr. Emily Germain-Lee. She's a scientist, and she also happens to be married to Se-Jin Lee.

SOFIA: Cool. Cool. OK.

HAMILTON: And Se-Jin and Emily actually met up as undergrads back in the late 1970s.

EMILY GERMAIN-LEE: We met when I was 18, and we were biochem majors in college together.

SOFIA: Oh, a little lab romance, a little Bunsen burner in the background, the hum of an incubator softly.

HAMILTON: It must have gone something like that.

SOFIA: (Laughter).

HAMILTON: And even then, you know, early on Emily, like, had these big dreams about things that she and Se-Jin might accomplish together someday.

GERMAIN-LEE: Wouldn't that be amazing if one day we worked on some project together that had incredible meaning and help people and, like, all the stuff that you'd think a teenage kid would say.

HAMILTON: So they went on to medical school together. Eventually, they got married. They had a son.

GERMAIN-LEE: Cute, cute. Go on.

HAMILTON: I know. And Emily became a pediatric endocrinologist, so she focused on rare bone disorders. And all this time, while Se-Jin was, you know, bulking up his mighty mice, she was treating children with diseases that affected their bones. And she noticed something, which was that weak bones could lead to weak muscles.

GERMAIN-LEE: My bone patients don't escape muscle loss because they have large periods of time where they can't move or a whole lifetime where they're wheelchair bound.

HAMILTON: And Emily says it also works the other way.

GERMAIN-LEE: Any muscle disease leads to weakness. And any weakness leads to bone fragility eventually.

SOFIA: So muscle loss and bone fragility go hand-in-hand.

HAMILTON: Yes. And Emily wondered something. She wondered if Se-Jin's work on blocking myostatin - you know, that protein that limits muscles growth - she wondered whether that might also help her patients.

SOFIA: Were they, like, talking about this every night around the kitchen table?

HAMILTON: Apparently they were, yes.

SOFIA: (Laughter) That sounds like scientists.

HAMILTON: Emily said other people thought she - might find her a little strange but that they found it gratifying to talk about these subjects.

GERMAIN-LEE: And part of it is just myostatin is threaded through our life. Se-Jin brings it home and talks about it not in a scientific way but in the way it has meaning. And it just became just really a part of me. And then...

HAMILTON: So the two of them realized that a drug that could strengthen both muscles and bones at the same time could help a lot of people. And that might include kids with muscular dystrophy or something called brittle bone disease, cancer patients, patients with hip fractures and older people who simply grow frail, and their muscles and bones get weak.

SOFIA: So they're starting to actually get to work together.

HAMILTON: Indeed. And eventually they identified a potential drug. This is a substance that affects not only myostatin but also other proteins that are involved in bone growth. And Emily, of course, wanted to test the drug on mice with brittle bones.

GERMAIN-LEE: I said oh, my gosh, I really have to try this. And Se-Jin said, sure. And those were the first set of experiments we actually physically did together.

SOFIA: Power couple, Jon.

HAMILTON: Right.

SOFIA: So how did the experiments actually go?

HAMILTON: Well, they worked. The mice developed both stronger bones and stronger muscles. And that initial success, it kind of paved the way for them to revive this idea that Se-Jin had been pursuing for, like, 20 years. This is an idea involving - wait for it - astronauts.

LEE: So for the astronauts in space, you know, they have lots of health things that they need to be thinking about. But certainly at the very top of that list would be muscle loss and bone loss.

SOFIA: Right. Right. Right. I know that people that go to space can lose, like, 20 percent of their muscle mass because there's not that much gravity up there.

HAMILTON: That's right. And space is actually the ultimate place to test something like the drug that Emily and Se-Jin were working on.

SOFIA: The final frontier, if you will.

HAMILTON: If you will.

SOFIA: (Laughter) You will not. Fine. (Laughter) OK, go ahead.

HAMILTON: So back in December, I went down to the Kennedy Space Center in Florida. That's where Se-Jin's mighty mice were about to launch into space.

LEE: We're getting close to the two-minute warning.

GERMAIN-LEE: I feel like our heart and soul is going up in that thing, you know?

HAMILTON: The experiment involved 40 mice with a month in near-zero gravity. And usually, that would cause, like, the bones to weaken and the muscles to pretty much melt away.

LEE: Question is, will they lose any of that muscle mass? And then if they do lose, then will they lose at the same rate as normal mice? Will they end up at the same place as normal mice, would they be somewhat protected and so forth?

SOFIA: So they basically want to see if the mighty mice lose muscle and bone density like the astronauts do? Or are they protected?

HAMILTON: Exactly. And there was something else. Se-Jin and Emily also sent up these mice that weren't genetically modified. They're these normal rodents, and they got the drug that Emily and Se-Jin developed together that builds both muscle and bone, at least here on Earth.

GERMAIN-LEE: I'm, like, so nervous (laughter). Here we go.

UNIDENTIFIED PERSON: (Unintelligible).

GERMAIN-LEE: Five, four, three, two, one.

UNIDENTIFIED CROWD: Five, four, three, two, one.

UNIDENTIFIED PERSON: (Unintelligible).

GERMAIN-LEE: Oh, my God.

SOFIA: Is that Emily?

HAMILTON: That is Emily. And so fast forward a month or so. Now the mice are back. And it'll take, of course, months for Se-Jin and Emily to know for sure whether they figured out how to maintain muscles without gravity. But I talked to them. And they say preliminary results are looking promising.

SOFIA: Oh, so things are kind of, you know, coming full circle for Se-Jin and Emily?

HAMILTON: It seems to be. I mean, from those college kids in the '70s to today.

GERMAIN-LEE: There was, like, this incredible connection. It's just part of who we are. And probably most people would think we're really odd, you know, but it's given great meaning to our life, I think, just knowing we've impacted a lot of people.

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SOFIA: Well, Jon Hamilton, thank you for bringing us this tale of space and muscles and a little science love story, pretty much everything we go for here on SHORT WAVE.

HAMILTON: My pleasure, Maddie.

SOFIA: And I'm absolutely bringing you back here to find out what happens with the cool mice.

HAMILTON: I can't wait to find out myself.

SOFIA: Today's episode was produced by Brit Hanson, edited by Viet Le and fact-checked by Berly McCoy. Thanks for listening to SHORT WAVE from NPR.

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