[MUSIC - DANIEL PETERSCHMIDT] JOHANNA MAYER: Hamlet. What does a mutation in the Hamlet gene do?
HELEN ZALTZMAN: Oh, depression, talking to a skull, really hating your uncle, being a small ham.
JOHANNA MAYER: OK, I'm going to cut you off. That was very impressive. From Science Friday, this is Science Diction. I'm Johanna Mayer. And today we're talking about gene names, fruit fly gene names, and also defenestration.
ELAH FEDER: Back in grad school, I spent a lot of time with fruit flies. I was studying evolutionary biology, doing experiments that honestly rarely worked out. I was not good at this very basic thing that you don't even have to be a scientist to do, which is keeping fruit flies alive.
JOHANNA MAYER: Science Diction Senior Producer Elah Feder.
ELAH FEDER: That is me. So I had some long days in the lab just sorting unconscious fruit flies under a microscope. And I was often bored. And to pass the time, I listened to a lot of--
[MUSIC - GWEN STEFANI, "HOLLABACK GIRL"]
GWEN STEFANI: (SINGING) Uh, huh, this my sh--
ELAH FEDER: --Gwen Stefani.
GWEN STEFANI: (SINGING) All the girls, stomp your feet like this. Few times you been--
ELAH FEDER: So "Hollaback Girl" was a big album at the time, but not everyone in the building was a fan of these beats that were coming down the hall. And one day, this professor from the lab next door suggested that I might listen to, like, anything else.
And he asked me if I'd heard of podcasts, which I had, but I wasn't totally sure what they were, and I was kind of stubbornly refusing to even find out. It sounded like some trendy new gadget. But I gave it a shot, which led me here. And in a roundabout way, I have fruit flies to thank for it. So today is a celebration of fruit flies, and we have company.
HELEN ZALTZMAN: I am Helen Zaltzman, and I make podcasts including The Illusionist, an entertainment show about language.
JOHANNA MAYER: And the occasion for all of us getting together? Fruit flies or, to be specific, their genes. Helen, so you probably have heard about how some people with COVID have been losing their sense of smell?
HELEN ZALTZMAN: Mm.
JOHANNA MAYER: Yes, very common. Last March, we came across this tweet from a professor, and he said that that loss of smell might be caused by this one particular gene getting silenced.
ELAH FEDER: Huh.
JOHANNA MAYER: And the gene was called Sonic Hedgehog. That was its real scientific name, which, of course, led to a lot of jokes, rightfully so, and also led to a lot of people being like, wait, you're allowed to name a gene after a Sega character?
And yes, actually, we do have a lot of genes with really weird names. So there used to be a gene called Headcase. And for a while, there was also a gene called Pokemon that was actually linked to cancer until Pokemon USA actually threatened legal action.
HELEN ZALTZMAN: They didn't want their name on such a non-playful gene?
JOHANNA MAYER: Yes, yes.
HELEN ZALTZMAN: But when people give those names to things, is that canonical? Or is it just what you use in your lab, being funny, and then in a-- in scientific paper, you give it a string of letters and numbers?
ELAH FEDER: No, that name will fully count. So you can discover a gene, give it just about any silly name that you want in your paper, and generally that's the official name. Although, there is actually, for human genes, a committee that's like the high court of human gene names. And they decide what names are actually OK and which ones are not.
JOHANNA MAYER: Because there are some that are not.
ELAH FEDER: Yeah, there are some that have caused some real problems, which we will be talking about. But a lot of those names, they're not the fault of human geneticists. It's actually fruit-fly geneticists who are the-- who are often the trouble makers and, also, mouse people.
JOHANNA MAYER: Yeah, the mouse people got in there and stirred up some stuff.
HELEN ZALTZMAN: Can't trust mouse people.
JOHANNA MAYER: But fruit-fly people in particular have a reputation for getting very creative with their gene names. Look, there's this article from 1992 in The LA Times all about this, this curious divergence between two camps of scientists, so fruit-fly people and sea-elegans people, AKA worm people. Worm people are dead serious with their gene names.
So when the fruit-fly people are partying it up with names like Drop Dead and Male Chauvinist Pigmentation, for the worm people, almost always, it's three letters followed by a number. And then the fruit-fly people are like, ugh, the worm people are total squares.
There's one guy who's actually quoted in the article. His name's Thom Kaufman. And he just straight up calls the worm people sticks in the mud.
THOM KAUFMAN: Oh, yeah. Well, my-- one of my favorite quotes is from a good friend of mine, Jeff Hall. You couldn't dynamite an interesting name out of a worm geneticist.
JOHANNA MAYER: Yeah, 29 years after this article came out, Thom Kaufman still stands by it. Today, he's a distinguished professor at Indiana University Bloomington.
THOM KAUFMAN: I prefer to think of myself as an extinguished professor, and I do flies. I love my flies. What can I say?
ELAH FEDER: He loves his flies.
HELEN ZALTZMAN: I'm really happy for him.
JOHANNA MAYER: So most people trace this tradition of weird gene names back to one guy.
THOM KAUFMAN: Thomas Hunt Morgan, the guy who started the whole thing back in 1910, when he discovered the White mutation.
JOHANNA MAYER: He's basically like the original fruit-fly geneticist, although he started off as a developmental biologist.
THOM KAUFMAN: And he kind of got dragged into this genetics business by happenstance. And it was recommended to him that he work on these fruit flies by one of his colleagues. And so he brought the flies into the lab because you could go out to the fruit markets and capture lots of them. And they just started breeding them.
ELAH FEDER: So Thomas Morgan, he didn't just study fruit flies. He ate them.
HELEN ZALTZMAN: Mm.
JOHANNA MAYER: He told his coworkers that they tasted like Grape Nuts, which is a cereal that I have never had.
HELEN ZALTZMAN: It's an austere cereal. It's like cat litter, but a bit scaled down.
JOHANNA MAYER: Yeah. Well, so that's why fruit flies taste like, apparently. So Thom had a different take.
THOM KAUFMAN: They taste pretty much like what they've been grown on, which is acetic and phosphoric acids. So mainly what the taste is is that.
ELAH FEDER: Like vinegar?
THOM KAUFMAN: Like vinegar.
ELAH FEDER: You sound like you know the taste of fruit flies from personal experience.
THOM KAUFMAN: Yeah, yeah.
ELAH FEDER: You've eaten fruit flies?
THOM KAUFMAN: Yeah.
ELAH FEDER: Why?
THOM KAUFMAN: Why not?
ELAH FEDER: They don't look appetizing. Did you season them? How did you prepare the fruit flies?
THOM KAUFMAN: Well, you just pop a couple in your mouth and--
ELAH FEDER: OK, so it's a finger food?
THOM KAUFMAN: --crunch them around a little and see what they taste like.
HELEN ZALTZMAN: Wow.
JOHANNA MAYER: I love how Thom Kaufman was like, of course, I ate them. It's the most natural thing in the world. Why wouldn't I eat them?
So Thomas Morgan, the original fruit-fly person, was breeding all these flies in his lab and snacking on them. And one day he noticed that there was this one fly with fully white eyes, one male fly with white eyes out of possibly thousands of flies. Fruit flies are usually red, but this fly had white ones, which that kind of thing happens when you're breeding flies in a lab, and they're all just getting really inbred. You start to see these mutations.
This male fly with white eyes turns out to be a very big deal because Morgan soon starts breeding these white-eyed flies, and he notices that the female flies are less likely to have the white eyes. It's usually just males, which leads him to show that genes can be sex-linked and, also, that genes are in chromosomes in a long string, which was really just a theory at that point. He actually ended up winning the Nobel Prize for his work.
But for our story, the key part is what he decided to name this gene. And this decision would set off a century of playful and sometimes very iffy gene naming. He named it White.
HELEN ZALTZMAN: Is that it?
JOHANNA MAYER: That was it. Yeah, that was it. The gene was named White.
HELEN ZALTZMAN: Oh, I thought it was going to be a noun.
JOHANNA MAYER: Nope, nope. That was it.
ELAH FEDER: But this was a turning point. It was a descriptive name in plain English, so he helped establish that tradition. And it was kind of an unusual choice.
STEPHANIE MOORE: It's a backwards logic because what we're expressing in the gene name White is what goes wrong when the normal function is absent.
ELAH FEDER: Stephanie Moore is a lecturer on genetics at Harvard Medical School and the author of First in Fly.
STEPHANIE MOORE: So if you have a normal copy of the White gene, you have a brick-red eye. It's a little bit like if you were naming parts of your car, and you called the steering wheel won't turn.
ELAH FEDER: So that also became a standard that Thomas Morgan helped establish, that you name a gene after what the mutant looks like. So still, naming things like White was pretty safe. And after that, people kept in the tradition of really safe descriptive names.
STEPHANIE MOORE: If we look at the genes that were named in the 1910s, 1920s, and so on, they look descriptive, right? They're descriptive of eye colors. They're descriptions of what's going wrong on a wing. A Forked is a forked bristle instead of a single bristle, right? So they're very straightforward. I would not be able to pinpoint who or when the field started becoming creative about it.
ELAH FEDER: But we do have examples where people start to get really creative with the best of intentions, and it winds up creating some awkward situations, like this gene. In the late '70s, a pair of scientists were looking at mutations that affected development. So fruit-fly larvae have bristles on them, and they found this one mutation that caused the bristles to be all bunched together. And they thought, what does this bristly little creature look like? Let's call it Hedgehog.
THOM KAUFMAN: Perfectly descriptive of the mutant phenotype. Everything is fine. OK. But then they found that there were mutants in mites, and mice have four copies of this gene. And the mouse people got cute, so they started naming these extra copies and said, oh, there's one that's Hedgehog, then there's one we'll call Sonic Hedgehog after the cartoon character.
And there's another one called Desert Hedgehog and Indian Hedgehog to name all four of these things. There's also Tiggy Winkel Hedgehog and Echidna Hedgehog. OK. And people were just trying to be cute.
ELAH FEDER: But humans have these genes, too.
THOM KAUFMAN: Well, then it was discovered that this gene caused a human disease that is a very bad thing for a child to inherit from its parents, holoprosencephaly. And when a child has this, and a doctor comes and says, oh, your child is mutant for the Sonic Hedgehog gene, well, it's not a joke to have a child with holoprosencephaly.
Another place where this is a problem is there's another mutation called Fringe. It was discovered in flies. And Fringe, again, has a mutant phenotype that's consistent with-- it's like Hedgehog. But then they discovered these extra copies of these genes, and they started getting cute. And so they called them Lunatic Fringe and so on.
And it starts to get a little over the top. And again, these things have human orthologs, which can be associated with bad genetic disorders in human beings. And so that's where things start getting a little dicey.
ELAH FEDER: This is where you really run into trouble. Sonic Hedgehog, great for jokes, works on Twitter, not great for medicine.
HELEN ZALTZMAN: I was just going to say that it often strikes me as a problem in medicine that the terminology is either too incomprehensible to non-medics, because it's in Latin, or it's eponyms, or in this case it's too fun. So maybe you need something that is actually quite boring in the middle, boring but plain.
ELAH FEDER: Well, it seems like we might be taking a sharp turn into Boringville now. When this work started, no one had sequenced a gene. They were just figuring out chromosomes. So it made sense to name genes after what the mutation looked like.
THOM KAUFMAN: Now that we have a sequenced genome, we're getting away from naming a lot of these things after mutant phenotypes and just naming them after the gene product it is.
ELAH FEDER: Which means naming it after a protein. The Lunatic Fringe gene obviously had to change, so that's now called--
ELSPETH BRUFORD: Peptide-3-Beta-N-Acetylglucosaminyltransferase.
ELAH FEDER: Wow. That's Elspeth Bruford of the Human Genome Organization's Nomenclature Committee. They're kind of like the adults in the room. So usually, people go with whatever name scientists have picked and published in papers. But when we start getting into names like Lunatic Fringe or Manic Fringe-- that's another one-- they will override that. And they've done that for a bunch of names over recent decades. So that's how we get--
ELSPETH BRUFORD: Peptide-3-Beta-N-Acetylglucosaminyltransferase.
ELAH FEDER: Which is, just from a practical perspective, very hard to say. It's hard to remember. I've already forgotten it, and I have it written down in front of me. And it's kind of sad that we're going this way. Obviously, we don't want to have names that are offensive or awkward for clinicians, but it does seem like creativity, within reason, brought people a lot of joy.
So is this-- is the era of descriptive or possibly silly gene names coming to a close because we can always describe the protein instead?
HELEN ZALTZMAN: Well, I mean, I don't think it will ever stop in fruit fly, but-- and don't get me wrong, some are just so well entrenched that we just don't think it's a good idea to change them. So you've maybe heard of the gene Sonic Hedgehog in human--
ELAH FEDER: Yes.
THOM KAUFMAN: So Sonic Hedgehog is such an incredibly well known gene name, and it's not actually offensive. Some people might think it's a bit frivolous, but it's not actually offensive. So there's such a huge body of literature already referring to that genus Sonic Hedgehog that to even think about changing it would quite honestly just not be feasible.
ELAH FEDER: Yep, so Sonic Hedgehog, that's not one of the names that got changed. It's not inherently offensive like some of the others, but also not great in the wrong context. Oh, and we should mention that it probably is not involved in the loss of smell that we see with COVID patients. We talked to a researcher about that.
But in any case, it seems like the era of creative gene names is not completely over, which is a good thing for people like Stephanie Moore. When she named a gene, she called it something descriptive but safe. There was a gene called Mago Nashi, which apparently means without grandchildren in Japanese, and Stephanie found another gene that interacted with it.
So she gave it another Japanese name, Tsunagari, which apparently translates to connection. And that seems like a good compromise. If you found out that you had a mutation in your connection or relatedness gene, you're probably not going to be offended by that name.
JOHANNA MAYER: Yeah. I mean, that's kind of I feel like what Thomas Morgan was doing in the very beginning by just calling it White or Apricot or whatever.
HELEN ZALTZMAN: Maybe it needs to be like what three words because you're going to run out of White, Apricot fairly quickly. But if you have fairly humdrum words in random combinations-- say, three of them-- then you do have so many options.
ELAH FEDER: So a random benign word generator?
HELEN ZALTZMAN: Yeah. Then you do have to program that carefully so it is benign. Ah, no wonder they call them just some numbers. Stay out of trouble.
[MUSIC - DANIEL PETERSCHMIDT]
JOHANNA MAYER: All right, so you've heard all about all of these fruit-fly genes. Elah and I are now going to tell you the name of a real fruit-fly gene, and you will try to guess what happens when there's a mutation in that gene.
HELEN ZALTZMAN: OK.
JOHANNA MAYER: Number 1, Spaetzle, as in the delicious German noodle.
HELEN ZALTZMAN: OK. Does it make a fruit fly look like a noodle or covered in a cheesy substance?
JOHANNA MAYER: Very close.
HELEN ZALTZMAN: Oh, poor fruit flies. Do they have wiggly legs?
JOHANNA MAYER: You were closer before.
HELEN ZALTZMAN: Oh, cheesy.
JOHANNA MAYER: So it makes their larvae look irregularly shaped like a spaetzle noodle.
HELEN ZALTZMAN: Wow, that's just going to ruin spaetzle for people.
JOHANNA MAYER: Absolutely. Do you know what their larvae usually look like?
HELEN ZALTZMAN: I don't Tell me a food they look like.
ELAH FEDER: I would say like tiny, skinny grains of rice.
HELEN ZALTZMAN: Yeah, I'd say basmati rice.
ELAH FEDER: They could totally blend in with your rice.
HELEN ZALTZMAN: Yay.
ELAH FEDER: All right, Helen, next one. There is a gene called Ken and Barbie.
HELEN ZALTZMAN: Is it very heteronormative, but asexual?
ELAH FEDER: It sure is.
HELEN ZALTZMAN: They have no genitals?
ELAH FEDER: Well, I think it's that they remain inside the fruit-fly body, no external genitals.
HELEN ZALTZMAN: Oh, wow. Oh, wow.
ELAH FEDER: Right?
HELEN ZALTZMAN: God.
JOHANNA MAYER: OK, this next one is one of my favorites, The van Gogh.
HELEN ZALTZMAN: Oh, mm. Well, I'm hoping it's something to do with art and not severing the larva's own ear.
JOHANNA MAYER: You're correct. Keep going down that path.
HELEN ZALTZMAN: Painting? OK. Are they very swirly and brightly colored, yellow, like the night sky? I'll just cycle through the van Gogh paintings that I know. Self portraits?
JOHANNA MAYER: Yes. You're very, very-- yes. Every fruit fly, it compels them to paint self portraits. No, you were very close. So a mutation in this gene causes the hair on their wings to grow in a swirling pattern--
HELEN ZALTZMAN: Wow.
JOHANNA MAYER: --very similar to the style of his paintings.
HELEN ZALTZMAN: Cool.
JOHANNA MAYER: I know. That's kind of a nice one.
HELEN ZALTZMAN: Well, it sounds nice, but maybe having swirly hair inhibits flight. I wouldn't know.
ELAH FEDER: OK, Helen, what do you think Clown is?
HELEN ZALTZMAN: Terrifying. It's a terrifying gene that makes people cry when that fruit fly turns up for a birthday party.
ELAH FEDER: Actually, Johanna did indicate as part of the answer that this was somewhat terrifying.
JOHANNA MAYER: Yes, I have a note that says horrifying.
HELEN ZALTZMAN: Do they live in a drain and lure you down there with balloons? Do they have big squeaky feet? Do they have an exaggerated facial expression painted on them?
ELAH FEDER: It allows more fruit flies than usual to fit inside a tiny car. The actual answer is eyes that are a mosaic of red and white.
HELEN ZALTZMAN: What?
ELAH FEDER: Why is that Clown?
JOHANNA MAYER: Because clowns wear the red and white checkers.
HELEN ZALTZMAN: In the eye though? Why don't chessboard?
JOHANNA MAYER: I think clowns typically have red-and-white-checkered suspenders. That is my image of a clown. You can submit that depending on what the abbreviation is.
ELAH FEDER: No, Clown is OK, although this is-- I could see Clown being another one that would cause problems if there were human orthologs.
HELEN ZALTZMAN: Yeah, true.
JOHANNA MAYER: OK, last one, Hamlet. What does a mutation in the Hamlet gene do?
HELEN ZALTZMAN: Oh, depression, talking to a skull, really hating your uncle, being a small ham?
JOHANNA MAYER: OK, I'm going to cut you off. That was very impressive. OK, so it affects the development of something called 2B cells.
HELEN ZALTZMAN: Oh, no. That's some crossword clue type of stuff.
JOHANNA MAYER: So you either have 2B or you are not 2B.
ELAH FEDER: It's so good. Come on.
JOHANNA MAYER: It's art. This one is art.
ELAH FEDER: Before we go, we have a question from a listener.
JOHANNA MAYER: So this word, I have received more emails about this word than any other word. Almost every time we ask you all to tell us what word you're curious about, someone mentions this one.
ELAH FEDER: OK, I'll read out this email. I would love to know if there's an origin story to my favorite word, defenestration, the action of throwing someone or something out of a window. It's oddly specific, so it makes me laugh. Thanks, Alicia.
JOHANNA MAYER: Yeah, there is a word specifically for throwing somebody out of a window. So defenestration comes from the Latin word for window, fenestra. And versions of the word defenestrate actually already existed in Middle French and German-- of course, Germans had a word for this-- as far back as the mid 1800s, but it's generally believed that defenestration entered the English language for the first time after a particular historical event where people were thrown out of windows.
So 1600s in Prague, there's a lot of turmoil going on. And in 1617, Roman Catholic officials closed a bunch of Protestant chapels. A lot of people were ticked off because they'd been promised religious freedom in this fancy agreement called the Letter of Majesty.
So on May 23, 1618, a bunch of Protestants got together, tracked down the officials who were responsible for closing these chapels and, also, their secretary who somehow got roped into this, and they put them on trial and found them guilty for violating the Letter of Majesty. And then they threw them out the window. It was the window in Prague Castle, and they fell for 18 meters, which is about 60 feet.
Somehow, they survived and weren't even seriously hurt. No one's totally sure how they managed to survive. I've read accounts that they landed in a pile of trash or even dug, but can't confirm those. And it's more likely that the wall against the side of the castle was sloped, so possible they ended up sliding.
This event became known as the Defenestration of Prague, and it actually ended up kicking off the Thirty Years' War. Now this is not the only example of defenestration in history. It seems like it was actually a pretty common form of punishment, but we can thank this particular event for giving us the English word.
And it lives on in the digital world. Computer scientists use the word defenestration to refer to bad-intentioned hacking of the Windows operating system. So thank you, Alicia and all the many, many, many other people who emailed me about this word. As always, if you have a question about a word, you can email us at firstname.lastname@example.org or call us up and leave us a voicemail.
The number's 929-499-WORD. That's 929-499-9673. We might play it on the show. Helen Zaltzman is the host of The Illusionist, a very fun and good podcast about language.
ELAH FEDER: We also talked to Helen about another beloved creature, the ladybug. You will soon be able to hear that conversation on her podcast, The Illusionist.
JOHANNA MAYER: Science Diction is produced by me, Johanna Mayer.
ELAH FEDER: And me, Elah Feder.
Daniel Peterschmidt is our composer, and they mastered this episode. Nadja Oertelt is our Chief Content Officer. And she says she knows our office has become infested with a horrifying human-mouse hybrid and that she was definitely going to exterminate, but then--
THOM KAUFMAN: The mouse people got cute.
ELAH FEDER: So now we peacefully coexist and feed them cheese. See you soon.
[MUSIC - DANIEL PETERSCHMIDT]