Conflicting Directives Sow Confusion For NIH Workers | The Mycobiome

The acting head of the NIH reportedly pushed back against legal guidance to resume grant funding, leaving federal workers in the lurch. Also, though fungi make up a tiny part of the human microbiome, they play an important role in both the prevention and development of many diseases.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Flora Lichtman?

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• 1:24Ira Flatow?

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• 1:43Flora Lichtman?

  This is Science Friday. I'm Flora Lichtman. Five weeks into the Trump presidency, federal science funding in the US is in a state of confusion. Executive orders that have halted grant funding at the National Institutes of Health, the NIH, have faced court challenges. Last week, a federal judge lifted a freeze on some NIH funding. So is the NIH making new grants? What's the directive? It's opaque from the outside. Is it any clearer on the inside? Catherine Wu, staff writer for The Atlantic, talked to nearly a dozen former and current NIH officials to find out what's happening on the inside of the NIH campus. She's here to catch us up on that and other science stories of the week. Katie, welcome back to Science Friday.

• 2:27Speaker 03

  Always good to be here.

• 2:28Flora Lichtman?

  So there's a lot going on and you actually spoke to NIH workers about what it is like to try to do their jobs. What did you find out?

• 2:38Speaker 03

  Yeah, I think it is fair to say that this has been one of the worst five-week stretches in a lot of NIH officials' career. It is just a mess in there. I think they are battling a lot of really conflicting things. They are telling me that they are caught between their duty to their direct leaders, including their acting director, what is legal according to the literal law in this country, and their duty to the American public to protect and preserve and promote their health.

• 3:09Flora Lichtman?

  Who is the acting director? Who's running the NIH show right now?

• 3:12Speaker 03

  Right, so for the past few weeks, it has been a flu researcher named Matt Memoli, who was kind of picked out of a part of the NIH that does not typically yield acting directors. There actually usually is a deputy director who typically steps into that position when directors are in transition, but that didn't happen.

• 3:33Flora Lichtman?

  And why was he picked?

• 3:35Speaker 03

  So I can't say for sure. I'm not in the brains of the people who did the actual selection, but the rumor mill suggests that it was for largely political ideology reasons. Matt Memoli gained some note of fame a few years ago when he emailed Anthony Fauci criticizing COVID vaccine mandates and that became public. He publicly critiqued the idea of COVID vaccines, reportedly refused the shot himself, at least in 2021. And he's also gotten sort of chummy with Jay Bhattacharya, who is Trump's nominee to lead the NIH next. And I was made aware that he submitted a DEI statement for an internal review at the agency where he called the term DEI offensive and demeaning.

• 4:21Flora Lichtman?

  Okay, so is the NIH making grants right now? Like, what is the state of grant making?

• 4:27Speaker 03

  Oh, gosh, I think the answer is sort of? Question mark. And I think that's actually a pretty fair assessment. I mean, normally, we see tens of thousands of grants come out of the NIH every year. And there is still kind of a trickle. It's been happening in fits and spurts. It's been really, really stop and go at the agency since, basically, the end of January. But it is nowhere near the typical cadence that is necessary to support biomedical research in this country and frankly, abroad. So the big issue here is that they have been told by their leaders, including Mamali and the folks at the Department of Health and Human Services, which oversees the NIH, that they are not to be issuing grants.

• 5:09Speaker 03

  And that is to be in compliance with President Trump's recent state of executive orders, including ones on DEI, gender, foreign aid, environmental justice. Basically, the agency is not supposed to be funding grants that would violate those orders. But they've also been told by federal judges, it's not legal to be withholding those federal funds. We allocated those funds to you as a country, and you were supposed to be giving them out. So it is a total and complete mess.

• 5:40Flora Lichtman?

  And what about, are there sort of competing directives within the NIH?

• 5:46Speaker 03

  So within the NIH, I would say that if you are looking to leadership, the message has largely been the same. Hold off, we're figuring things out, we're trying to do our best to comply with President Trump's wishes. But I think the mixed messaging really comes from the fact that their leaders are telling them one thing, but these are also government workers. They, of course, you know, find the letter of the law very important, and all around them is this swirl of, you know, federal court orders that are saying, no, you really need to get back to business as usual to comply with the law. That is the most important thing. You must unpause things immediately.

• 6:24Flora Lichtman?

  And what about the NIH lawyers? What are they saying?

• 6:27Speaker 03

  Well, the NIH lawyers are certainly experts in the law and they have been advising leadership, yeah, please follow those court orders. If they're telling you to unpause and get back to grant making, that is what you need to do. That is what is most legally advisable. And at worst, if they continue to violate some of these court orders, they could be held in contempt, they could be prosecuted as criminals. But I think people are really unsure what to do. If their leadership is telling them one thing, their lawyers are telling them another thing, agencies are telling them kind of something else, court orders are saying yet another thing, it's a mess. I mean, some people appear to have resigned over this mess.

• 7:03Flora Lichtman?

  Is this also happening at other agencies, NSF, EPA?

• 7:08Speaker 03

  I believe this has been happening to some degree at every federal agency that you could name. But I think what makes NIH particularly special is the size of its budget, which is about $47 billion a year, and the fact that their pause has probably been one of the most prolonged and severe. You know, just for sake of comparison, the National Science Foundation, NSF, they resumed a decent degree of grant making as early as February 2nd. Things are by no means completely perfect and running smoothly over there. But just for comparison, I think that shows that federal agencies are handling this very, very differently, depending on their leadership, depending on who is overseeing that particular

• 7:49Speaker 03

  agency, and likely, you know, what staff internal to the agency are attempting to accomplish in this mess.

• 7:56Flora Lichtman?

  Let's talk about the measles outbreak in Texas. What's the state of that?

• 8:01Speaker 03

  It is not great. As of this week, we have hit triple digits in terms of the number of confirmed cases. An unvaccinated kid has died amid the outbreak, which is the first measles death that the country has recorded in over a decade. It's incredibly tragic. I mean, this is a dire situation. This is one of the bigger outbreaks that we've had in recent years. And I'm already hearing experts talking about the fact that this could be an outbreak if it continues to grow in size and the deaths continue. This could be something that could lose the country its elimination status for measles, which we declared in the year 2000.

• 8:39Flora Lichtman?

  I need a break from our planet for a second. It's a pretty special weekend for stargazers, right?

• 8:46Speaker 03

  Yeah, absolutely. I fully agree. Life on Earth is super stressful right now. I am constantly trying to look elsewhere. And tonight, I mean, I need to sort of check if my zone of habitation is in the right spot. But for some lucky people, if they have the right stargazing equipment, they can look upward and may be able to see all seven of the other planets in our solar system.

• 9:09Flora Lichtman?

  Oh, the planetary parade.

• 9:11Speaker 03

  Yes. And I will say, like, having some degree of what's called planetary alignment, which is, you know, being able to see more than one planet up in the sky at any given time, isn't like, super rare. But to have all seven of the other members of the solar system up there at once and potentially visible, that's pretty cool.

• 9:30Flora Lichtman?

  I read that it won't happen again until 2040.

• 9:33Speaker 03

  Yeah, so if this is your jam, I would definitely get in there. You're gonna be waiting a long time.

• 9:42Flora Lichtman?

  Okay, let's move on to one of my favorites from the week. A glass brain. Tell us all about it.

• 9:48Speaker 03

  Oh, yes. So if you are an archaeology nerd, you may already know about this glass brain that was uncovered from the region that was, you know, seriously impacted by the Mount Vesuvius eruption 2,000 years ago. And I do want to note that this isn't quite in Pompeii, but it's adjacent to Pompeii. But basically, researchers a few years ago found what looked to be nerve tissue that had glassified. What happened this week is researchers came out with a paper that suggested a new explanation for how the brain tissue could have glassified. And the big problem before is, to get glass, you need to heat something very, very quickly and then cool it very, very quickly. That's typically what

• 10:32Speaker 03

  happens with like, the molten sediment that we use to make like, the glass we see in our homes. But that wouldn't have happened very easily with an eruption like this. So the researchers said, well, maybe it wasn't all the like, thick volcanic debris you're picturing when you picture an eruption. Maybe in advance of that, this super hot cloud of ash hit this poor guy who was lying down in his bed, glassified his brain, and then dissipated really quickly because it was just ash. It could move really quickly. And that's how the super fast heating and cooling happened in that short timeframe.

• 11:03Flora Lichtman?

  All right, I'm lacing up my running shoes. Well, in my case, my slow, slow jogging shoes for our last story. Researchers have crunched the numbers and think that Kenyan runner Faith Kipjigan could break the four-minute mile? Is this a big deal?

• 11:19Speaker 03

  Oh, it would be a huge deal. So no woman has been recorded doing this. A man broke the record. Well, multiple men have broken the record as early as the 1950s. But to have a woman break this record as well would be not only just another amazing feat of human performance, but I would also hope would be really inspiring to people across the gender spectrum, just to think like, this is not one of those things where, oh, a man can do it, but a woman can't. I think that's an incredibly important message to send. So the idea here is, I mean, she is close, but also not close. Her record is four minutes and 7.64 seconds. And to non-runners, that may not sound like a lot, but to people who are sprinters,

• 12:03Speaker 03

  that is a huge chasm to be breaching. And so people have been really skeptical that this could happen. I mean, she currently holds the world record for a woman, so she is an incredible candidate. But it would be really tricky. What these researchers are saying is what might be the trick is to have really strategically placed pace setters during a race to basically be in front of her and in back of her to reduce drag. So, you know, the force that would be working against her from like wind resistance and all that stuff. But if you have strategically paced people, you're basically able to draft off of those people and run to your maximum ability without having to battle as many external forces as you otherwise would.

• 12:44Flora Lichtman?

  What did Faith have to say about this?

• 12:47Speaker 03

  So I believe she was interviewed by The New York Times on this, and I think she called it interesting. I don't think she really wanted to. I suspect she didn't really want to guarantee that this was going to happen or not. But she seemed to be very gracious. I mean, if someone did this modeling study on me, which they definitely wouldn't because I'm the world's slowest runner, I would also say it was intriguing, but like TBD on what's going to happen next.

• 13:14Flora Lichtman?

  Thanks, Katie. Thanks for joining us today.

• 13:16Speaker 03

  Thanks so much for having me.

• 13:17Flora Lichtman?

  Catherine Wu is a staff writer at The Atlantic. Before we go, next Friday is the Stand Up For Science Rally in Washington DC and across the country. Are you planning to go? Tell us about it. How far are you traveling? Is there a crowded van involved? And why are you going? Call us or text us at 646-767-6532. That's 646-767-6532.

• 13:47Flora Lichtman?

  After the break, you've heard of the microbiome, but how about the mycobiome? A researcher makes the case for why the fungus among us is vital to our health.

• 13:56Speaker 04

  Bacteria and fungi, they interact together and they play together.

• 14:07Speaker 05

  Science Friday is supported by PBS, presenting Going Wild. If you love learning about the natural world and meeting the scientists who help us understand it, be sure to check out the new season of Going Wild with Dr. Ray Wynn Grant. It's the chart-topping and Webby Award-winning podcast from the folks at Nature on PBS, now with a video companion series. In this season of Going Wild, host acclaimed wildlife ecologist Dr. Ray Wynn Grant heads out into the field to explore the animals, people, and stories that make nature worth saving. Stops include a hibernating black bear den in Arkansas and an underwater shipwreck site off the Florida coast. If you're looking for a place to start, check out the season's debut episode, where Ray joins beloved biologist and influencer

• 14:49Speaker 05

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• 15:32Speaker 05

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• 15:40Speaker 06

  And from the Alfred P. Sloan Foundation, working to enhance public understanding of science, technology, and economics in the modern world.

• 15:52Flora Lichtman?

  When I hear microbiome, I think of the billions and billions of bacteria that call my body home. But the microbiome is more diverse than that. It includes viruses and parasites and fungi. And that last group doesn't always get a lot of attention. Partially, it's a numbers thing. Fungi are outnumbered by bacteria about 1,000 to 1 in the microbiome. But even if they're a smaller sliver of the population, according to my next guest, that does not meet our fungal friends and foes are less important. When your fungal feng shui is off, things can go afoul. Fungi can play a role in Crohn's disease, irritable bowel, celiac diseases, colorectal cancer, and more. Our next guest has been banging

• 16:37Flora Lichtman?

  the drum for fungi for many years. Over a decade ago, he coined the term "mycobiome" to shine a spotlight on these misunderstood mycelium. Dr. Mahmoud Ganum is a microbiologist and professor at Case Western Reserve University's School of Medicine, based in Cleveland, Ohio. Welcome to Science Friday.

• 16:56Speaker 04

  Thank you for having me.

• 16:59Flora Lichtman?

  Let's start with the basics. How do you define the microbiome?

• 17:03Speaker 04

  As you mentioned, in our body, there are microbes that live in and on our body, on the skin, in our gut, all over the place.

• 17:15Speaker 04

  One important community of these microbes is the microbiome. And as you know, my ecology is the study of fungus. So we coined the term microbiome to refer to the fungi that live in our body.

• 17:31Flora Lichtman?

  No one had coined that term before.

• 17:33Speaker 04

  Nobody have coined this term before us. And really, it came from the fact that for many, many years, I worked with fungus. And I always knew that bacteria and fungi, they interact together and they play together. So about 15 years ago, when people were talking about the microbiome, they talk about bacteria. I told them, no, no, no, you really need to talk about fungi as well, or the fungus that live in our body. And that's where I thought it would be a good idea to differentiate the bacterium, which is the bacteria, from the microbiome, which is the fungus.

• 18:16Flora Lichtman?

  Did it work? Did people heed your call?

• 18:19Speaker 04

  You know, it's so funny you ask this question. For a long time, people did not listen. I wrote an article in 2010 that we should look at both of these communities and nobody listened. 2016, I also wrote another article in the Scientist saying the microbiome, basically, the ignored kingdom. And lo and behold, I published a paper after that to look at the microbes that live in the gut of Crohn's disease patients. And I showed that not only bacteria is there, but also fungi are there. And they really interact together and they help each other.

• 19:03Speaker 04

  After this, people start reaching out to me, asking about the fungal community. And really, they needed guidance, how we can help them to rebalance. And that's where people start to take really the microbiome into consideration. In fact, 2021...

• 19:26Speaker 04

  Also, the National Institute of Health opined at that time to say, "Yes, we really need to look at not just bacteria, but about the other communities out there." And that's really pleased me tremendously because it took them a decade, but they figured it out at the end.

• 19:45Flora Lichtman?

  Well, how do fungi and bacteria interact with each other in the microbiome?

• 19:49Speaker 04

  What happens when they are together? You can imagine, they are not like in suspension. They stick together. They adhere to the tissue in our gut, okay? The gut lining, for example. And then what they do? They start secreting some chemicals or metabolites that can change their behavior. In fact, to give you a specific example, we found that E. coli and Serashia marssisans are two bacteria. They interacted with Candida tropicalis, which is a fungi, and they formed what we call biofilm. You know what a biofilm? It's like the plaque in our teeth.

• 20:29Flora Lichtman?

  I was just gonna say, yes, I know about it from my teeth.

• 20:32Speaker 04

  Exactly, but nobody described them in our gut, how they interact together to really cause our issues with Crohn's disease, for example.

• 20:43Flora Lichtman?

  In a biofilm in your gut, what should I be picturing?

• 20:48Speaker 04

  The best way to imagine a biofilm, it's like a jello. Inside this jello, you have M&M's or raisins, okay?

• 20:56Flora Lichtman?

  You're speaking my language, Mahmoud.

• 20:59Speaker 04

  So you have the jello is the matrix. Matrix is what these raisins and bugs inside the jello produce, okay? It's made of carbohydrates, proteins, some DNA, and it becomes like a cover or an area which protects this organism. Not only this, when they interact together, these bacteria and fungi, we showed in animal models as well as in vitro or test tube experiments that the shape of the candida changes. So if you have a plaque... Or biofilm of candida alone, it's in the shape of yeast, like baker's yeast, okay?

• 21:42Speaker 04

  When you put them together with the E. coli and serasha, they form what you call filaments or hyphae, or like thread-like, thread-like material. And what happens, this thread-like material, they start to poke holes in our gut lining. And that's why we have leaky gut. And they are protected from antibiotics or antifungals because of the matrix which we talked about, the jello, as well as they are protected against our immune cells. You find the immune cells are unable to go in and kill these bad bugs.

• 22:19Flora Lichtman?

  Wow, so they're working together in some cases?

• 22:21Speaker 04

  Yes.

• 22:22Flora Lichtman?

  You know, we hear a lot about how antibiotics wreak havoc on our microbiome. And I think, when I think of that, I think about the effects to bacteria. But has modern medicine changed our fungal makeup?

• 22:34Speaker 04

  Yes, definitely. You know, you will laugh at this. I am an old man, I am seventy-five next May. I did my PhD or doctorate fifty years ago, okay? The fifty years ago, my project was how antibiotics and steroids can affect candida. In other words, when you use an antibiotic, what happens? You kill not only the bad bugs or the bad germs that causing disease, we kill also the beneficial one, which keeps candida under control, okay? So that's why, when you use an antibiotic, definitely it wreak havoc in your gut balance.

• 23:19Flora Lichtman?

  You know, we hear about these good bacteria. Are there good fungi?

• 23:22Speaker 04

  Yes, certainly. Thank you for asking this question because a lot of the time, people think of fungus as a bad thing. Apart from the mushrooms, of course, people love those. Now, we have good fungi or good yeast, like...

• 23:37Speaker 04

  Saccharomyces circisae. You remember Saccharomyces circisae is what we use to bake our bread and make beer. And we found in healthy people, we have high level of this good yeast or good fungus.

• 23:51Flora Lichtman?

  Wait, if you're healthy, you have a high level of bread making and beer making yeast in your body?

• 23:56Speaker 04

  Yes, yes.

• 23:57Flora Lichtman?

  Do we know what these good fungi are doing?

• 23:59Speaker 04

  Yes, we know, of course. Remember, I am a fungi, I know a lot about fungus, okay? So, what they do, they can control the ability of candida to grow.

• 24:13Flora Lichtman?

  And candida is like the fungus we know is associated with yeast infections and thrush. We don't want that one out of control.

• 24:20Speaker 04

  We don't want that out of control, but I love the word you said, "out of control." Why? Because if you look at people in general, healthy people, or you have maybe 50 to 70% of us have candida in their gut. If it is at low abundance, it's no problem. We can take care of it because the good guys can keep candida under control. The problem starts when we kill these good guys. This gives candida the opportunity to overgrow. And lo and behold, when it overgrows, believe it or not, what it does, it keeps the good guys down. So as if we killed the policeman and we keep the policeman under control.

• 25:03Speaker 04

  That is not good for us.

• 25:06Flora Lichtman?

  Okay, so the beer bread fungus keeps the bad guys under control. What I'm hearing you say is that this is an argument for drinking more beer and eating more bread.

• 25:16Speaker 04

  Unfortunately, biology is not as simple as this, okay? I agree with you, having a beer is great. So you don't want to take the message from me here that go and drink about five, six beers a night. So yes, having little alcohol is good, but not too much of it.

• 25:31Flora Lichtman?

  Do we have to worry about antifungal resistance, the way that we worry about antibacterial resistance?

• 25:39Speaker 04

  Certainly. I tell you something, you are asking good questions. I'm praising you now.

• 25:44Flora Lichtman?

  Don't butter me up. I know, you know what you're doing here.

• 25:47Speaker 04

  Why? Because you touched on a topic now, which now is becoming hot. The anti-fungal resistance. We all know about the antibacterial resistance. It's time to think anti-fungal resistance. There was a new fungi that cause infection in the skin, discovered in India, which is resistant, highly resistant to tirbanefin, one of the major drugs we use to treat nail infections. And lo and behold, we are starting to see it in the U.S. as well. And there was big interest from the CDC, asking people to submit applications to understand what is the extent of really spread in the U.S.

• 26:32Speaker 04

  I tell you, this is an area that needs to be addressed because in addition to antibacterial resistance, we have now anti-fungal resistance.

• 26:41Flora Lichtman?

  Why do you think the microbiome has been overlooked for so long?

• 26:47Speaker 04

  You know, because for a long time, we did not have a lot of fungal infections. Okay, it was mainly bacteria. But what happens? We change medicine, the way we practice medicine. I'll give you a simple example. When you have cancer, you are treated with chemotherapy, radiation and all this stuff. And guess what happens? You lower the immunity of the patient. And when a patient has low immunity, this gives the opportunity for fungi to cause infection. That's why we call it opportunistic infection. They take the opportunity, when somebody's immunity is weak, it starts.

• 27:31Speaker 04

  And that's why now we are seeing more fungal infection than we used to see, uh, let's say, forty, fifty years ago.

• 27:41Flora Lichtman?

  And so now people are paying attention.

• 27:43Speaker 04

  I hope so.

• 27:44Flora Lichtman?

  Thank you so much for this fascinating conversation.

• 27:47Speaker 04

  You are most welcome. It's a pleasure to talk to you.

• 27:51Flora Lichtman?

  Dr. Mahmoud Ganum, microbiologist and professor at Case Western Reserve University's School of Medicine, based in Cleveland, Ohio.

• 28:02Flora Lichtman?

  And that is about all we have time for. Lots of folks helped make the show happen, including

• 28:08Speaker 01

  Jordan Smudgick.

• 28:09Ira Flatow?

  Charles Bergquist. George Harper. John Dankowski.

• 28:13Flora Lichtman?

  I'm Flora Lichtman. Thanks for listening.