Science Friday - BRCA Gene Test, Bacteriophages, Synesthesia. March 9, 2018, Part 1

Episode Date: March 9, 2018

Overuse of antibiotics has lead to bacteria becoming resistant to the drugs. In the United States, at least two million people become infected with antibiotic resistant bacteria each year, according to the Center for Disease Control. While some researchers are looking for new sources of antibiotics, other scientists are looking for new strategies to treat bacterial infections. One strategy is the use of bacteriophages—viruses that infect and kill bacteria.  In 2013, the Food and Drug Administration prohibited the consumer genetic testing company 23andMe from marketing a test for breast cancer mutations and drug sensitivity. Now, the FDA has changed its mind, granting 23andMe permission to screen for three mutations in the BRCA1 and BRCA2 genes, which increase breast cancer risk. Around four percent of the world’s population has some form of synesthesia, a neurological phenomenon that blurs some of the lines around the senses. In two of the more common variants, synesthetes may involuntarily associate letters with colors, or see colors for musical notes—but there are many other forms of synesthesia, all involving the crossover of one form of perception to another. This week, researchers report that they’ve identified several regions of the genome that may be involved in synesthesia. Plus, Maggie Koerth-Baker, senior science reporter for Fivethirtyeight.com, tells Ira about a falling space station, exoplanets, and more top science stories of the week in the News Round-up. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Flato. A bit later in the hour, how a virus fished out of a lake healed a man's deadly infection. But first, this March is a great month for night sky gazing. I'm going to get out my telescope because Mercury and Venus will line up close to each other, low in the horizon. You have Jupiter, Mars, and Saturn also being bunched together. And if you're lucky, you might catch another bright spot in the sky, though it's not a planet or a star, it'll be a falling space station crashing to the Earth,

hopefully not near you. Maggie Gerthbaker is here to fill us in on that story. She's senior science reporter at 538.com. Welcome back, Maggie. Hi, thanks for having me. Well, we know the station is going to come crashing down somewhere, but how many more details than that? I mean, that's all we know, right?

Scientists have left it pleasantly vague. So sometime between March 29th and April 9th, and somewhere in a area of the world that covers Spain, France, Portugal, Greece, and I quote, et cetera. Et cetera. It's good that's right, the escape clause. Now, the Chinese space agency was using the station for five years, right? What was it used for? For basic scientific research, there was part of their push to become a space space. faring power, the first Chinese woman in space went there, and they apparently lost control of it somewhere

around 2016. So now it is descending to Earth without anyone being able to guide it to some other place that's not populated. Yeah, I remember covering NASA skylight falling from in 1979. There was always stuff coming back down to Earth. Well, there's always stuff coming back down to Earth. There's probably about one piece of space junk that falls to Earth every day. Most of it is not. not this big. The chunks of this space station could be as big as 220 pounds. But the good news is that in this entire history of space junk falling to Earth, there's only ever been one person that we know of that got hit with space junk. And that is Lottie Williams of Oklahoma, who got bopped on the shoulder by a six-inch-long fragment of a second-stage Delta rocket

back in 1997. She was fine. Bopped. That's how he... She got bopped. by that. Okay. I hope she was not more, you know, we'll move on. Let's move on to a study out this week. I looked at the representation of women's scientists when it comes to the big journals. This is a month we're talking about it. What did it find? So this was an analysis of prestigious multidisciplinary and neuroscience journals, and it showed women were underrepresented, underrepresented, rather, as published authors in these journals. And that was even compared to the rates at which women receive prominent research grants, the kind of that end up funding the research these journals tend to publish. So, for instance, when the study looked at nature, they found that women accounted for fewer than 15% of last authors on papers published in nature, which that usually means the most senior person involved in the research.

and 27% of NIH National Institute of Health and UK Medical Research Council grants were going to female lab heads. So you have 27% of these big grants going to women researchers, but only 15% of the papers in nature were representing those women. The authors also found a negative correlation between a journal's five-year impact factor and the percentage of first and last authors that were women. So basically the more big deal of journal is, the fewer women are getting past the gatekeepers. And do we know why the disparities between the grants and the publications? They have not speculated on that. This isn't the first paper to show gender imbalances in scientific publishing. There have been quite a few over the last few years that showed various types of gender imbalance,

both on editorial staffs and in publications and also in reviewers. And they did, though, make a suggestion that maybe what we need to do is have more mandatory double-blind reviewing, because there's apparently been a couple of studies that show that mandatory double-blind reviewing actually seems to reduce those gender imbalances in what's deemed worthy for publication. That's interesting. Let's move on to coral reefs being affected by warming oceans. We know that they're shrinking or dying, and scientists have found another effect of eroding corals.

Right. So we know that coral reefs have been shrinking. They've been dying. Part of that is from warming oceans. Part of that is from human intervention. I mean, people touching them, getting sunscreen chemicals on them. All of those things can hurt and kill them. But we also know that coral reefs dissipate the energy from waves.

And because these reefs form near islands, it ends up affecting the people that live on those islands and the communities that are on those islands. So as corals become more stressed, they grow less slowly. or excuse me, they grow more slowly and they become less complex. So combined with rising sea levels, that could mean big trouble for these low-lying coastal communities that have depended on reefs for protection from big waves. This new analysis shows that by 2100, the average wave height at several locations in the South Pacific could be more than two times higher than it is today, exacerbating that flooding

from the rising sea levels, even more. And then you have shrinking corals and rising waves and sea levels. It's not good news. No. Yeah, let's move on to something that's kind of interesting also that you're going to talk about. That's that there's been a flare-up with one of our neighboring exoplanets. It was a candidate for life. I was rooting for this one.

Everyone was rooting for Proxima Centuary B. It's so close, isn't it? It is. It's only 4.2 light years away. It was found in 2013. It's in the habitable zone around its star. It's this candidate for extraterrestrial life. but unfortunately some recently published research has found some bad news about Lil B.

It probably got fried last year sometime in March. That is because its sun, Proxima Centuri, got a thousand times brighter than normal for about 10 seconds on March 24th, 2017. And most likely that means a massive solar flare. So 4,000 times the radiation Earth usually gets from the sun blasted out all at once at this little planet. As one of the scientists told science news, that means that the planet is likely not in the best shape. That's a euphemism for being toast, literally. A little bit, yeah. And it also sort of implies that this could be something that happens fairly frequently with Proximus Centauri,

which would really put a damper on life on Proximus and Cherry Bee. No hope, then. No hope for it. I wouldn't say no hope, but it definitely makes it less likely. I like that because, you know, with four light years away, you know, you could have a conversation. back and forth in a lifetime. And that's... Yeah.

That's very sad, Maggie. Thank you. Well, I'm glad we kept that for last. I'm happy to provide you all the depressing news. Oh, no, you can't even come close. Maggie Gertz Baker is Senior Science Reporter for 538.com. Thanks. And now it's time to play.

Good thing, bad thing. Because every story has a flip side. Five years ago, the Food and Drug Administration sent the genetic testing company, 23 and me, sent them a... warning letter. Stop marketing your personal genome test, they said. Stop telling your customers about their breast cancer risk, their drug reactions, and so on. The reason, what if the results from that mailed-in-saliva sample were wrong? Patients might get unnecessary surgery or think they don't have a cancer risk when they really do. Well, now the FDA has finished

reviewing data from the company and has changed its mind, reversed its decision, and freeing the company to tell customers about whether they have the breast cancer brachian gene mutations. Here to tell us the good in the bed is Emily Mullen. She's associate editor for Biomedicine at MIT Technology Review, and we love MIT Technology Review here at Science Friday. She joins us via Skype. Welcome. Thanks so much for having me. So give us the good news here. So the good news here is that this test reports on three mutations in the Bracca 1 and Bracca 2 genes.

which are associated with a high risk of developing breast and ovarian cancer. And these three particular mutations are most common in people of Ashkenazi Jewish heritage. About one in 40 people of this heritage has one of these three variants. I think probably the biggest benefit of this test is also its biggest drawback,

and that's the fact that you don't have to visit a doctor for this test. This is going to be an additional result that's available to customers, under 23MEE's existing health and ancestry tests, which costs about $199, actually exactly $199. So you say that is the good news and the badness. So what's the bad news about that?

So the bad news, there's a big caveat here, and that is that there are 1,000 or more known mutations found on the bracket genes. And the three variants that 23 and me test for are not the most common ones in the general. population. So what that means is a negative result for these three mutations reported by 23 and me is not a negative result for all BRAC mutations. In other words, if you test negative for these three mutations, it doesn't rule out a higher risk for cancer. So one worry is that a negative result could give people a false sense of security that they don't have an increased risk of cancer. And there's another concern that, you know, women who test positive might go out and

have unnecessary screening tests, and more alarmingly, they could end up getting mastectomies or even having their ovaries removed in the hope that they'll prevent breast or ovarian cancer. We actually saw something like this happen before, so you'll probably remember that a few years ago, Angelina Jolie went public about how she got a preventive double mastectomy after testing positive for a BRCA mutation. And what happened after that was sort of this Angelina Jolie effect. More women went out and started getting tested for the BRCA gene, and more women, you know, are starting to get preventive mastectomies.

That's a really big personal choice that probably, you know, shouldn't be hinged just on this 23-meat test. Yeah, because I remember when we started talking about gene testing way back in the day, we said, you know, there's going to be a problem if you get a test, result and you don't know how to interpret it, you should either be offered a doctor or professional care or you should go out and seek some guidance on this. Right. And that's the concern, I think, with this new 23 and Me test result. You know, when you go to your doctor to get a genetic test, somebody, whether it's your doctor or a nurse or a genetics counselor, is going to sit down

with you to tell you what those results mean. Now, the FDA, as you mentioned, is definitely softening to the idea of these at-home genetic health risk tests, but what the FDA is requiring is that companies communicate results in a way that consumers can understand and use. Emily, thank you very, very much for taking time to be with us today. Emily Mullen, Associate Editor for Biomedicine at the MIT Technology Review. After the break, we'll talk about the problem of antibiotic resistance. Could viruses be a key to figuring out the antibiotic problem? It's an old technology that's being reborn. We'll talk about it after the break, so stay with us. This is Science Friday. I'm Ira Flato. Our next story is about a virus fished out of a lake

that healed a man suffering from an antibiotic-resistant infection in his heart, saved his life. A little backstory first. You've heard that there is an antibiotic resistant infection in his heart, saved his life. You've heard that there is an antibiotic crisis, right? We all know that, more and more bacteria are becoming resistant to the standard drugs. In fact, in the U.S. alone, 2 million people each year develop infections that cannot be treated by the usual antibiotics. So the rush is on to find new antibiotics. Some scientists, though, are turning to an old technique that was being investigated before World War II, before the age of antibiotic wonder drugs, enlisting viruses.

called bacteriophages, viruses that seek out and kill bacteria in nature. They do it all the time. Well, now back to that patient. He was given a dose of a bacteriophage, a virus found in a lake. And he healed. He was healed in a matter of days. The scientists who found that phage published their results this week in the journal, Evolution Medicine, and Public Health. So could we engineer phages for novel treatments. Why not let nature do the work for us? And are we finally in the age where we can say the phage is all the rage? And how to get that in there, sorry. Let me introduce my guest. Benjamin Chan is an author and that study from Yale University. Welcome to Science Friday. Hi, Benjamin. Are you there?

Yeah, I'm here. Hi. Thanks for having me. I want to also bring on Timothy Liu, Associate Professor of Electrical and Bioelectronic Engineering at MIT. Welcome to Science Friday. Hi there. Thanks for having me. Hi there. Now, Benjamin, this patient you treated came to you as a last resort. How did you hear about this patient?

I heard about him through sort of the hospital administration. When I first popped into the university, I sent emails all over and, you know, saying, hey, I'm new here. I'm really interested in doing some of this stuff. And like the former head of the hospital got back to me and said, I think you should talk to these people, forwarded me along, and to Deepak Narayan, also an author on the study. And he just, when I spoke to him in his office, he said,

ah, I've got, you know, I've got a case you could, you know, you should look at and see if we can do something about this. Did you already know that you had a virus of phage that could combat this infection? Well, I had lots of bacteria phages, right? So when I first arrived, I started collecting them from all over different sources. But I didn't know for sure that it could work on his strain until I actually got the strain from him. So you injected the phages directly into the infected area, right? Close.

Well, how did you know how to do it and where to put it? How much, what size dosage, all those things? Well, we didn't, to be totally honest, because it's not known. Like it hasn't been done before in this. of indication, and so we were sort of, it was a lot of guesswork, but that was based on a lot of evidence that we sort of came up with in the lab, where we tested the minimum, you know, a minimum number of phages required to kill an approximate number of bacteria, which we estimated. And so we did a lot of pre-work in the lab and then just estimated that maybe 10 to the eighth

would be sufficient. And now you're a phage hunter, right? You go out into the slime and the muck and you look for these naturally occurring. viruses? Yeah, I go all over. A lot of times it's, you know, the muck and the slime, but, you know, sometimes it's nice lakes and rivers as well. And this was, and this one was found in a lake. Yeah, in a lake here in Connecticut. Wow. Dr. Liu, you're a synthetic biologist, your engineering phages that get around the antibiotic resistant problem. How do you, how do you build these fages, they use the phage coat, the package that you want that's inside there? How do you make a phage?

Well, what we do is we take the genetic material that's inside that phage. It basically is the software program that actually encodes all of those phage components. And our focus is then how do you pluck things out of that phage genome for your application of interest, or how do you insert new materials into that phage genome so that you can endow that phage with new functionalities, for example, use in therapeutics or even as diagnostics. Do you need Benjamin's library to be able to build your phages? Well, I think certainly Benjamin's library and many of the libraries that are being discovered by the phage hunters are really valuable for the sort of work that synthetic biologists want to do. You know, there's an amazing diversity of genetic material out there that have evolved over time of these phages have been countering bacteria and vice versa.

And that starts as a great starting substrate for the types of engineering that we'd like to be able to do. At number 844-724-8255. You can also tweet us at Cy Frye, talking about the... using phages. This is not, as I mentioned before, this is not a new idea. Didn't the Soviets work on this before World War II and have laboratories where they were trying to create bacterial phages that sort of went out of fashion when the areas of these miracle antibiotics came about? Sure, yeah. Bacteriophages have been developed as therapeutics for almost 100 years now. and the work persisted in sort of the former Soviet Union

where it faded out here after the discovery of broad spectrum antibiotics. And when you go out to look for a phage, Benjamin, do you go looking for a specific thing that you just go into out there and say, hey, let's see what I can pull out of the lake today? A little bit of both, I guess. For some of the phages we're looking for, we have a pretty good idea where they won't be. And so we can sort of tailor our search.

We study, like, you know, cholera as well. And so you have to go to a location that actually has cholera in order to find the phages. And Tim, what do you do to create a new phage? Give us a process as involved. Yeah. So as an example, some work that we've done before is to take that phased genome, which nowadays with DNA sequencing technology, has been fully read. and so we can then identify specific locations where we'd like to pop in additional genes that would endow, for example, that phage with the ability to break up biofilms more effectively

or reduce that bacteria's ability to develop antibiotic resistance. Then, depending on what tools you want to use, we can use tools like CRISPR to cut out DNA from that phage and insert our new DNA in that. Or even if we can use some of the new DNA synthesis-based technologies and print that DNA from scratch and actually insert that into the phased genome. We then take that now recombinant or a new phaged genome, and we can then insert it back into the bacteria that actually is the host for that phage. And when that DNA goes in, it sort of boots itself up and can generate a new copy of that bacteria phage now with the additional functionality that we've encoded into that bacteriophage.

I find an ironic that you use CRISPR against the bacteria because CRISPR is what the bacteria uses against the virus, is it? Yeah, I think the amazing thing about phage biology in general is not only has it this great potential as a therapeutic agent, but it's actually phage biology, plus the interaction between phages and bacteria has really been a really rich source of all the tools that we actually use in modern-day molecular biology, ranging from some of the things that gave rise to CRISPR or those studies that gave rise to our basic understanding of molecular biology and how to manipulate it.

So, you know, these phages are everywhere in the environment, and I think they've really made a big impact in biology, even beyond the use in antibiotic resistance. Benjamin, so how was this particular phage you use? How was it able to knock out this type of bacteria? So this particular one we're using, we used as sort of a way to drive a force of tradeoff, right, between antibiotic sensitivity and phage sensitivity. Because early on we found that when bacteria became resistant to this phage, that they suddenly were now susceptible to antibiotics.

And so we forced sort of a trade-off where we anticipated bacteria becoming resistant to this phage, but as a consequence, it would be susceptible to antibiotics. Why aren't more drug companies doing this kind of thing? Well, I mean, it's complicated, I guess, like all things, But I think a major part of the problem, I guess, for a company whose interest is, you know, profit is sort of intellectual property. As far as I can tell, that's a bit harder when you're looking at live organisms. But I think, you know, with synthetic organisms or whatever or engineered ones, you can get around that problem. Tim, can you patent a phage that you're making?

Yeah, I think you can get intellectual property coverage over things that are manipulated. So I think that that is one piece of the puzzle. But as Benjamin also mentioned, it's a complicated problem. I think in general, antimicrobial drug discovery is underfunded compared to other areas of research. And, you know, if an antibiotic works the way it should, it should cure that patient in just a few days. And it's not something that's going to generate, you know, years or decades of profits for a pharmaceutical company. So I think in terms of the way the current incentive system is set up, it's not really conducive for, you know, the types of, you know, the types of, you know, profit-focused drug development that many companies focus on.

And so there have been interesting discussions about alternative approaches to try to incentivize antimicrobial drug development, since it's really, if you think about antimicrobies are sort of a public good in that, you know, if I use an antibiotic too much, it actually affects your future ability to use that same antibiotic. And so maybe we have to think about more creative ways to incentivize drug development in this area. Is one of the obstacles that these phages are very specific to one bacterium? These aren't broad spectrum treatments. You have to make it, you know, it's not a shotgun.

It's a very precise shot here, Benjamin? I mean, it can be. I think that's a massive benefit because, you know, you're not going to disrupt any of the microbiome. And you can use the specificity of bacteriophages to sort of target-specific, you know, proteins or sugars or whatever you're looking at or virulence factors on the bacteria surface so that when they become resistant, You know, you've sort of made them less able to cause disease or antibiotic susceptible.

So I think the specificity is a massive benefit for using phages therapeutically. You know, we talk a lot about the microbiome here, the bacteria that's in our gut a lot. I would imagine, tell me if I'm wrong, if there are all these bacteria in there, they're going to be phage viruses trying to attack them also. So we have a lot of viruses lurking around in our gut. Can we engineer phages that might help our microbiome? Tim, what do you think? Yes, I think certainly, I think there are a lot of phages and other viruses that are actually

present in our microbiome. They're relatively understudied compared to the bacterial members of that community. But if you think about it, many of the approaches we have now to manipulate the microbiome, including antibiotics, are not very narrow spectrum. There's no really ready way for us to say, I want to knock out this one specific bug from inside my gut. And so I think the development of narrow spectrum targeting agents, like bacteriophages, can be very useful in that process to really allow us a greater tool set to be able to manipulate the bacteria

that are inside of us. Let's go to the phones, 844-8255 to South Bend, Indiana. Hi, Brian. Hey, I'm curious, is there any chance for these phages becoming pathogenic to the patient? And if so, you know, how do you manage that immune response that the patient would have against the treatment? Good question. So, I mean, as far as we know, there's no bacteriaopages that can infect or attach to human cells,

since they're very, very, very specific to particular strains, often of bacteria. And managing the immune response, maybe Dr. Liu could answer since he's a physician. Yeah, I mean, I think the immune response for foreign elements in the body is certainly something to consider. You know, I think in many of these cases, giving them as an acute treatment, you know, the, you know, as we've seen from some of the studies that Benjamin has published in others, you know, I think there's an immediate sort of risk benefit to be able to use these, especially when there's infections that are not present. There have been strategies to try to shield these bacteria phages from the immune system,

you know, covering them with certain polymers are actually mutating the phages so that they can hide from the immune system to a greater extent. To my understanding, there haven't been significant adverse effects been reported with the administration of phages from that perspective, but it is a concern that I think anyone who's using these should be aware of and continue to monitor. I'm Ira Flato. This is Science Friday from PRI, Public Radio International. Talking with Benjamin Chan and Tim Liu about the bio of the phages. What if a doctor has a patient and wants to get in contact with you, Benjamin?

And so here's this story and says, you know, I have patients all the time who are at the end. We run out of antibiotics. Are you open to hearing from them? Is there a data bank? Is there a place for people to go? Yeah, of course I'm open to hearing from them. I actually heard from one late last year. I mean, I hear from them fairly regularly,

but we actually treated a second case in December of this year with some great results. So I mean, Google me or, you know, I should be in the first 10 pages or so and email me. And I'm just surprised that we don't hear more cases. You know, one, two, if there's so many people, there are so many, you know, infections that can't be treated. I would think people would be flooded with calls looking for phage therapy. Is that surprise you with that journey? I mean, I get quite a few calls for it. So I wouldn't say it's not flooding my inbox, but I think it's more of a process than we realize.

I mean, the FDA is great, actually. The process works in getting approval for these. But a lot of times it's getting the strain from the person and sending it to a lab where they're going to find, test their phage on it. And there's a little bit of a delay there. But that's going to change, you know, in the future as it becomes more accepted and there are banks sitting around or the fages are more characterized. Dr. Liu, am I just being naive about all on this?

Yeah. Well, no, I think it is an area that is quite exciting. I think, as Benjamin mentioned, there is a process currently in terms of the way it's done. And it's, you know, I think there's a lot more work to try to make it systematic and expand the scope of what can be achieved. I think one of the current challenges is, as was alluded to earlier, really the diagnostic challenge, how do you know you have a phage on the shelf that will go after the bacteria of interest? And inherently, there's a time lag associated with that.

And if we want to push the use of these phages to the front line of medicine, we need better tools to diagnose the infections rapidly and then be able to pull the phages off the shelf to know that those will be actually effective in the patients we want. So I think over time, if we want to see the broad utility of this, you know, despite the great work that the labs like Benjamin's and all the other, others are doing, they won't be able to service, I think everybody in the country who might want to do this, especially once more people start hearing about this, and I think we're going to need sort of more high throughput and quicker processes to be able to execute on the vision here.

In the minute I have left to have somebody on the phone like that, R.B. from Fort Dodge, Iowa. Hi, R.B., welcome. Good afternoon, gentlemen. I recently went to my doctor of infectious diseases, and he told me that I had MRSA, and I was probably going to be on doxas cycling for a year. My wife, who's in medicine, shook her head on me, like, this is not great news. I was surprised at how many people have Mercer. I didn't even know what it was. I need a question quickly because we're running out of time.

Okay. Any thoughts they have about Mercer and Phages? Okay. Why not use phages to treat Mercer? Go ahead. I mean, it depends on the infection, right? Of course, and the nature of it. But there's lots of phages that can infect and kill Sephora,

including MRSA, and it's just sort of matching the right phage with the right infection. So it's done on a case-by-case basis. That's how you work. Currently. I mean, you know, as if we get through trials eventually, it could be like an approved thing that you just sort of would be available like Dr. Liu was mentioning. But right now it's case-by-case. Can we speed it up, Dr. Liu? Well, I think if we have more funding for great support and really can incentivize this area, I think, you know, the technology is there.

It's just a matter of getting the regulatory, getting the manufacturing, getting the scientists together, and really coming up with a strategy for rolling this out. Great way to end this conversation. Benjamin Chan, Associate Research Scientists in the Department of Ecology and Evolutionary Biology at Yale. Timothy Liu, Associate Professor of Electrical and Biological Engineering at MIT. Thank you both for taking time to be with us today. When we come back after the break, do you associate letters or days of the week with specific colors? Do you see colors when you hear music plays?

We'll talk about synesthesia after this. Stay with us. This is Science Friday. I'm Ira Flato. It's been estimated that around 4% of the world's population has some form of synesthesia. That's a neurological phenomenon that blurs the boundaries between the senses. Let me give you an example. In a common form of synesthesia, when people see letters, they also see colors or see colors when hearing musical notes. There are many, many kinds and many combinations, but all of them involve the crossover of one form of perception to another. This week, researchers report they've identified several regions of the genome that may be

involved in the phenomenon. Joining me now is Amanda Tillott, one of the authors of the research published this week in the proceedings of the National Academy of Sciences. She's a postdoctoral researcher at the Max Planck Institute for Psycholinguistics in the Netherlands. Welcome to the program. Hi, thanks for having me. You're welcome. Also with us is Ed Hubbard, professor of educational psychology

and the neuroscience training program at the University of Wisconsin in Madison. He's at WPR Studios in Madison. Welcome to Science Friday. Thank you for having me. Amanda, this is a pretty common phenomenon, but sort of at the same time, many people have never heard of it. I never really heard about it until we started researching this. Right.

A lot of people don't realize that their perceptions are anything unusual until maybe they hear about it in a book or in a neuroscience class in college. So that's actually a tricky thing. It's very common, but people don't talk about their perceptions with their friends and realize that there's something a little different. So people who have it grow up thinking everybody is like them? Often, yeah. Yeah. Is this the same thing as imagining deeper musical times? tones, notes as darker colors, or seeing music in a minor key as dark.

What is going on? Explain us. Yeah, so our thinking about this is that some of the same brain processes that are involved in, say, imagining the music as being dark or these sorts of things might be present both in people who experience anesthesia and in all the rest of us that don't experience anesthesia. But in people who have synesthesia, these processes are high. or exaggerated in such a way that they do this involuntarily. They often describe it as something that happens to them as opposed to something that they do.

And they report that it's been that way for as long as they can remember ever since childhood. So it's quite different at the level of sort of how it feels to you. That subjective experience, but we think at a brain level there might be a sort of continuum between what you and I might do voluntarily and what synesth each report experiencing. You know what's interesting is when we were talking about this in the office, some people in the office, and we have a small population of people just perked up and said, you know, I get that, I hear that. And one of our staff people said that she gets in trouble giving people in the New York subway directions

because the color, the MTA has assigned, let's say, to the A train, that doesn't match up with the color that she sees as that letter. Yeah, this is a quite common experience that, synesthetes will report that they have their own lifelong associations, and the rest of the world also tries to use color codes, but they don't match for any given synesthete. Amanda, you looked at several families of people with synesthesia. Who were they? And what did you find?

What were you looking for? So these are families that were originally identified about 10 years ago in a study done in the U.K., where they were using the best technology at the time. to try and understand if there were particular parts of the genome that were associated with synesthesia that might be the same across family. So a more unifying answer that would apply to everyone with synesthesia. And they actually had a really hard time finding something like that, which suggested that in individual families,

you might have different genetic causes. And so that's where the research left off. And we picked up a couple years ago coming back to these families with newer technologies that allowed us to get really precise. So we could look for specific single-letter changes in the DNA that would be associated with synesthesia in these families. So the people in the family who have synesthesia might have these changes. and the people who did not have synesthesia would not show those changes.

And we looked for those in each family separately. So is this genetically passed on from one member of the family to another? Yes, that's what we think. And we've had some indication that that was the case for about 130 years. So that idea that it runs in families is not new. But it's been taking a long time to figure out exactly what was happening. Well, well, what was happening? What did you discover is happening?

What did the genes do? So the genes that we found that contained changes that were specific to synesthesia, those were different in each of the three families. But we were kind of expecting that based on the previous research that suggested, this is going to be complex. This is not going to have one simple answer. And so our next task was to figure out if there were any functions of those genes that would tie them all together.

So maybe they're all different, but they act in similar biological pathways. Maybe they have similar roles, maybe even in the brain. And when we looked for that, you know, what activities were overrepresented in this big list that we had from the three families, we found that genes related to how neurons connect with each other during development, and how they know where to go to send their connections to link the right circuits together, that was a function that was overrepresented in our list of genes that were showing differences in the synesthetes. And that was surprising and exciting for us. Ed, how does this fit into what we already know about synesthesia?

So I think that this is a really nice sort of bridge between the genetic level and what we were learning from more systems level neuroscience, thinking about how the brain is organized. So one of the main theories about what's causing synesthesia is a story of sort of crossed wires in the brain that, for example, brain areas that are involved in recognizing letters and words lie directly adjacent to brain areas that are involved in perceiving colors. And so about 15 years ago, we put forth this idea that there was some sort of what we called cross-activation. So every time somebody who has anesthesia sees a letter or a number, in addition to activating those neurons in the brain that are involved in recognizing letters and numbers, they also activate some of those color cells in the brain. And that's why they then get this automatic, involuntary additional experience of colors. And that idea has been around, and it's been supported by various. different brain imaging tools. So looking at, for example, functional brain imaging, fMRI,

and also looking at the structure of the brain at a very coarse level, being able to look at how brain systems sort of look when we look at them with MRI. But this bridge, to be able to connect this up now with the molecular and cellular level and talk about these pathways at the level of these individual families, I think is really exciting. And I think that this is now allowing us to build these bridges across these different levels of explanation. Dr. Tillott, do we have any idea what's going on in the brain that sets these associations

initially, you know? That's a good question. So the ideas that are out there right now, and I think some of the more prominent hypotheses, are that something in your genetics, maybe differences in the types of genes that we saw, maybe differences in genes that we haven't identified yet, predispose the brain to form these extra connections. So your brain is primed to make these extra links between your senses. And then exactly what links form, you know, what color is your number six or your Wednesday is then an interplay with your environment. And that is something that has been looked at a

couple different ways, trying to see what environmental effects there are. But the idea is, so far, at least maybe that your brain is wired a little bit differently that makes it more receptive to these changes or to these associations. And then it's up to what you experience to form the rest. Let's go to the phones to Merritt Island, Florida. To Lee. Hi, Lee. Welcome to Science Friday.

Hello. Hi. Thank you for taking my call. I discovered that I have synesthesia when I was teaching a college-level composition course and I gave my students an assignment to write down what color the music was that I played and I played some pieces of music and not a single one of them understood at all what I was asking of them and when I received their blank looks I thought oh there's something wrong with me and I started doing some research and I realized this must be what it is I see colors I see

shapes and textures when I hear music and sometimes it's distracting enough that I can't listen to it while I'm driving because it's so vivid in my sight line, even though it's in my mind's eye, it's sometimes hard to see the road. And my son is very interested in music, and he's fascinated by this, and he wants to know, can you induce this in a person who doesn't have this tendency naturally? Is this something you can learn to do when you listen to music? A good question. Ed, what do you think? Yes, so this has been a question that's been around in the music.

the experimental psychology literature and then the neuroscience literature, almost as long as we've been studying synesthesia. So since the late 1800s, really, people have asked that same question. And the answer seems to be kind of. With lots and lots of intensive training, people can learn to have synesthesia-like associations. And a recent study has even shown that you get these really nice. systematic changes in brain activity along with these changes in people's report, but it doesn't seem to be quite as automatic.

It doesn't seem to be quite as stable. And the changes may go away fairly quickly after you stop the training. So there does seem to be something still different between synesthetes and non-cinesthetes in that respect. But those of us that are curious about it might find a way to at least get some insight into what it's like. Lee, are you still there? Yes.

Do you, does it help you? Do you think of yourself as more artistic because of, I'm going to call it a talent that you have with synesthesia? I think that I found artistic ways to express it. For example, from the time I was very young, five years old as I first remember, I was interested in dancing, and every time I would hear music, I would act out the shapes and textures that I would see with the music. And that turned into an ability to dance. And as a consequence, since I was 18, I've been a professional choreographer,

and I'm very easily able to choreograph, you know, dances to the music because I just, you know, close my eyes and watch the music and then, you know, teach people to do what I see. Wow, that's a great story. Thank you for sharing that with us, Lee. Thank you. Thanks for calling. I have a tweet here from Kim who says,

Both my husband and daughter have synesthesia. I read that it is thought we all have synesthesia as infants, but that the associations diminish or disappear from most people within their first few years of life. Have you seen any research regarding this idea, as fact she says? Do we all have it? And do some of us keep it and some of us lose it? What do you think, Amanda, Ed? Amanda, go ahead.

I can talk about the Dobkin study, or you can if you would like to. Oh, no, go ahead. I think that's one I was thinking of. Okay, Alphonse, you go. So there was a study that was done by Karen Dobkins and her team at the University of California, San Diego, and they looked at six-month-old infants and used a paradigm where they asked the infants to sort of look at the same shape over and over and over again until the infant got bored. And then they presented things that were colored and tested whether or not that boredom from the shape also transferred to the colors.

And what they found was that individual infants would associate, for example, triangles with red. So if they had seen a bunch of triangles, they were bored by red. And that suggested that the sort of cross-talk that is present for synesthetes between letters and colors might be present in infants. And then when they looked at, I think it was nine-month-old infants, that cross-talk seemed to go away. And so this does suggest that early in development, there is some of the same cross-talk that's important for synesthetes having their lifelong associations between letters and colors. This is Science Friday from PRI, Public Radio International. Now, Amanda, I understand you are studying synesthesia and you need volunteers, right? Yes, we do.

You have a big megaphone right here. How can people sign up? If you experience connections between letters and numbers or days of the week and colors, we would love for you to join our study. You can start by going to our website. It's www.m.m.m.l. slash synesthesia. And if you click on join the study, you can learn a little bit more about synesthesia, take some short quizzes if you're not sure.

and if your types that you experience are the right ones for our tests, we'll send you a genetic test in the mail, and you can mail it back to us. You can participate from anywhere in the world, and we pay for the shipping. There you go here. The website is samples.mpe.n.l. nl. slash synesthesia. We'll try to get up on our website later on. In the minute we have to go ahead, you're studying educational psychology. Now, does this affect the classroom, the synesthesia?

This is part of what we're looking at now. Synesthetes will say that sometimes their colors help them to remember things like phone numbers or math facts. They will also say that sometimes they get in the way when, for example, the colors for three and four don't mix to create the color that seven should be. Or two plus five, which are different colors, are supposed to give them the same color for the seven. So synesthetes say it helps them and hurts them in all sorts of interesting ways. And we're still trying to understand this. And so we're looking at adults, college students here that have synesthesia, and also looking at children trying to understand better how these synesthetic associations help and hurt their learning.

Good luck to both of you. Ed Hubbard, Professor of Educational Psychology, and Neuroscience Training Program, University of Wisconsin, and Madison and Amanda Talat, postdoctoral researcher Max Planck Institute for Psycholinguistics in the Netherlands. Thank you both for taking time to be with us today. Thank you, Ira. Thanks for having us. You're welcome. Before we go, I want to invite you to join me on April 9th for a special springtime celebration of the Green Space here in New York.

We'll be talking about one of my favorite subjects, orchids. We're going to have orchid experts and storytellers. We'll have drinks and food, and you might even get to take home an orchid that I select myself. You're going to love these orchids. To purchase the tickets for more detail, go to ScienceFriiday.com slash events. science Friday.com slash events, April 9th at the Green Space here in New York. And also a special

thank this week to Rachel Bouten, our events manager, who's been working very hard on our national breakthrough event series this month, celebrating women and science. Thank you, Rachel. We couldn't do this without you. We had technical help also today from Rich Kim, Sarah Fishman,

and Jack Harowitz. We are active all week on, oh, everywhere, Facebook, Twitter, Instagram, all the social media. If you have a smart speaker, to play Science Friday when you want to. So every day now is Science Friday. I'm Ira Flato in New York.