Science Friday - Picking Right COVID Test For Holidays, “Big Bang Theory” Of Cancer. Nov 19, 2021, Part 1

Episode Date: November 19, 2021

Here’s How Biden’s Infrastructure Bill Addresses Science President Joe Biden signed a massive bipartisan infrastructure bill into law this Monday. The measure focuses on a range of sectors. It would funnel billions into cleaning up pollution in the air and water with efforts that include eliminating lead service lines and cleaning up old, polluted manufacturing sites. The bill will also invest $7.5 billion to create a large-scale network of electric vehicle chargers across the country. In other big news this week, a new study confirms that masks are highly effective in combating COVID-19, reducing incidence of the disease by as much as 53% on its own. Researchers say this finding is significant and add that when masks are used in addition to other protective measures, like vaccines and hand washing, people can feel confident in their safety. Joining guest host Roxanne Khamsi to talk through these and other big science stories of the week is Nsikan Akpan, health and science editor for WNYC Public Radio in New York City. Happy (Holiday) Testing Season! The holiday season has snuck up once again, leaving many people to figure out familiar logistics: If travel will be involved, who to see, and what will be for dinner. But of course, we’re still in a pandemic, so questions of safety remain. At the end of the day, we want to keep our families, friends, and loved ones healthy. COVID-19 tests are becoming a popular tool, helping many people make social situations safer. Quickly swabbing your nose or spitting in a tube can indicate if someone has been infected with the coronavirus. But with so many options available, and a big season of holiday get-togethers up ahead, many are wondering what kind of test is best—and when is the best time to get tested? Joining guest host Roxanne Khamsi to talk through COVID-19 testing questions are Dr. Céline Gounder, epidemiologist and professor at New York University’s Grossman School of Medicine in New York, and Dr. Alex Greninger, assistant director at the clinical virology laboratories at the University of Washington Medical Center in Seattle. The Big Bang Theory Of Cancer Despite tremendous scientific advances, there’s still so much scientists don’t understand about cancer. One of the biggest remaining questions is how do tumors form in the first place? Researchers are getting closer to an answer. For years, the prevailing theory of tumor growth was that cancer cells gradually acquire a series of mutations that enable them to outcompete healthy cells and run amok. But improved genetic sequencing of cancers is revealing a more complicated picture. New technology has enabled a new theory of tumor development, called the big bang theory. It turns out that some types of cancer contain a whole hodge-podge of mutations right from the very beginning, even before the tumors are detectable on a scan. Researchers initially observed this pattern in colon cancer, and then replicated the findings in pancreatic, liver, and stomach cancers, too. Guest host Roxanne Khamsi talks to Christina Curtis, associate professor of medicine and genetics at Stanford University’s School of Medicine about her research into tumor development, and how to improve cancer diagnosis and treatment. 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 Roxanne Camsey. Later in the hour, we'll talk about COVID-19 testing ahead of the holidays, plus the Big Bang Theory of Cancer. But first, President Biden signed the bipartisan infrastructure bill into law this past Monday. In it is a lot of funding towards cleaning up pollution in the air and water. It'll also invest in public health measures with a focus on underfunded communities. There is a lot to unpack in this bill and how it relates to science. So joining me now to walk us through is my guest, Sikan Akpan, Health and Science Editor for WNYC Public Radio in New York, a friend of the show and a friend of mine. Welcome back to the show, Sikon. Hey, thanks for having me. Let's dive into this infrastructure bill.

I think a lot of people think about things like bridges and roads when infrastructure is brought up. But there's a lot of stuff here in this bill that's related to science. So what are some of the big things that stick out to you? Yeah, you know, this first, this infrastructure bill is massive. It's a huge investment in terms of cleaning up the environment. And Vox has a great breakdown of what, you know, the infrastructure investment in Jobs Act could mean for cleaning up pollution in different communities. You know, this is a $1.2 trillion act that passed after months of debate that actually gradually whittled down parts of the original American jobs plan. that President Biden released at the end of March. And, you know, when it comes to the environment

and climate change, that process left some big winners and some big losers and also what I would call some big wait and see policy decisions. But still, this new law comes with some clear winners and losers. So who are some of the winners? So the biggest winner is arguably cleaner air near highways and urban areas. So the Infrastructure Act comes with about 2.5 billion for electrifying school buses. There's also 17 billion for reducing pollution near ports and inspiring the production of like electrified tugboats and freight trucks, you know, the types of things that we see moving in and out of industrial areas. The electric grid is also a huge winner. So there's 65 billion devoted towards modernizing the grid and also building it out, sort of expanding it into

new places. I think that could be particularly helpful with fighting wildfires in California. So, you know, part of the Monday will be used to take those like power lines, those transmission lines that we see sort of running overhead on poles and bury them underground where they can't spark fires. Expanding the grid would also put the country in position to build more renewable energy plants and, you know, then just plug them into the grid. And I think in that vein, there's about $500 million for new nuclear and hydrothermal projects, as well as some carbon capture for fossil fuel plants to make them a little bit more carbon-friendly to the degree that they can be made carbon-friendly. And there's also $6 billion for large-scale battery production.

Wow. I mean, it sounds like there's a lot of focus on fighting pollution and things like that, but you alluded to the fact that there are some losers as well. Can you tell us a little bit about that? Yeah, so, you know, the biggest loser might be Biden's original Americans' jobs plan that was released back this spring. So the Sierra Club put together a nice table of where that plan started in terms of its funding for environmental and climate investments and where we are now. So those investments currently are at 46% of what Biden originally proposed, if you consider the money that's in the new law and also what's being proposed in the last. latest version of the buildback better bill that's under consideration. I think carbon control is also probably another loser. We have, we're facing this climate emergency where we need to reduce carbon emissions as fast as we can in order to stop all of these disasters that we already are already kind of

saying. And so, you know, Vox cited a Princeton analysis that suggests that the infrastructure law would only reduce carbon emissions by 1% by 2030. know, the build-back better build might aid that mission, but only if some of those environmental pieces can survive the House and Senate deliberations. And, you know, there are a lot of other things in that build, like paid family leave and also like a lot of child care funding that, you know, is going to be strongly debated. So we'll have to see if the climate elements survive. Hmm, it sounds massive. So let's move on to some other massive news about COVID-19. And there's been a study out confirming what a lot of us have thought to be true, that masks work. Can you tell

us a little bit about this new study? Yeah, you know, the Hill had this new story about this study with the headline, huge new study finds masks most effective public health measure in fighting COVID-19. And I just want to, I want to just do a quick fact check on that headline because, you know, they're saying, oh, it's a massive analysis of 72 studies across the world that was published this week. But in truth, you know, what we're talking about is a system, systematic review. So, you know, it's a group of researchers who tried to find all the papers they could on this topic, you know, and this topic we're talking about is technically called non-pharmaceutical interventions, right? So, you know, masking, social distancing, the types of stuff that we can do

around behavior to reduce the transmission of infectious disease. So this review started with about 36,000 papers that they just screened to say like, okay, is this on the topic of public health measures for COVID-19? From there, they whittled that down to about 650. And then they were like, okay, were these studies well designed? Do they have, like, you know, potentially too much bias? And then from there, they got down to 72 papers. With mask wearing, it showed that it can reduce the, it can essentially cut the incidence of COVID-19 in half. which is good to know, right? Like, you know, there's been a lot of debate about wearing masks in public.

You know, I think we've created this sort of false paradigm between getting the vaccine and taking off your mask. But I think this is really showing that masks are a valuable part of how we keep people safe, especially in scenarios where they can't socially distance. Because, you know, we know that the vaccines are very good at stopping infections. They are extremely good. at stopping severe disease, but we still get breakthrough infections, even though they're very rare. And so I think if we can reduce that even further, it would put us in a better place overall to break coronavirus transmission for good and then, you know, be able to really reopen safely. And cutting risk by half is quite a lot, although vaccines seem to do even more when you

compare them separately, but combining these things together, I guess, is the point? Yeah, I mean, I think we take the results for the vaccines, right? We know that if you have just like, you know, your two shots of Pfizer and Moderna or Johnson and Johnson, you're going to reduce your chances of infection by 80 to 90 percent, depending on which vaccine you're taking. If you get a booster, we know, okay, it's popping you back. It's like, oh, you're so much better. You have way more immunity. So then you're lowering your chances of infection even by more, right, to like 95%, back to where we originally were before Delta decided to power through. So they're saying both are doing well, right, but together they will combine to sort of give

extra layers of protection to everybody. Speaking of getting vaccinated, the FDA today authorized COVID booster shots for all U.S. adults. The CDC still needs to sign off on this, but it's a big step. And we'll be talking about boosters later in the show. But let's move on to another vaccine for now. One against Lyme disease, which is really interesting to me because I grew up in New England and Lyme disease was definitely something we all talked about.

Yeah, you know, Lyme disease is a long-term scourge and infects a lot of people, right? Like close to half a million every single year in the United States. Most people are going to survive it. They're going to be completely fine. But there is, you know, a proportion that develops chronic Lyme disease and it can become very problematic for them for years. So this vaccine is interesting because it is an MRNA vaccine, right? So like Pfizer-Moderna, the vaccines against COVID. What's cool about this mRNA vaccine is that it's essentially trying to create an itch response. So what it's doing

is it's targeting the proteins that are in the saliva of ticks and ticks carry the germ that causes Lyme disease. And so what they've seen in guinea pigs is that, okay, you vaccinate them, and then you put a tick with Lyme disease on the guinea pig. And it creates these like itch marks, like these like rashes. And so the idea would be that, okay, if it was a person instead of a guinea pig, they would be like, oh, what is this? Like I'm, oh, I'm itchy right here. Oh, there's a tick on me. And then you pull the tick off. And what we know about the transmission of Lyme disease is that it typically takes about 36 hours from the tick bite. The tick is just sitting there, sucking blood. It typically takes 36 hours. And so if you can catch that tick early enough, you can reduce

transmission. And so that's what they found with these guinea pigs. Like once they saw the itch marks, they pulled the ticks off and they were like, oh, these guinea pigs didn't develop Lyme disease or they didn't catch the bacteria. So that sounds really interesting. It sounds like the vaccine is keeping the ticks from getting in or doing their nasty thing before the Lyme disease bacteria can get in the body. I do think that it's time for a little bit of a story about some cute animals since we were talking about some nasty ticks. One thing that's come across the radar this week is there's a lovely story about ducklings. Sikon, can you tell us about the latest duckling news we've been blessed with?

Yeah, so this is from one of my favorite science writers at Emily Conover. She spotted this study from Scotland where they tried to figure out why a mother duck and her ducklings will swim in a row. And so what people should know about is like when you swim, when you do like a stroke, you know, you're doing like the freestyle in the Olympics, right? When you push against the water with your hand, the water is actually pushing back. And when you create waves, those waves when they hit you are actually pushing back against you. So that front stroke that you do with your hand can actually create a wave that pushes against like the back part of your body and slows you down. And so the same thing happens with ducklings, right?

So they're splashing along and they're making a wave that is also pushing back against them. And so what this study did was it sort of created a model to show that by swimming in a straight line, the mother duck is creating a wave in her wake. but if a duckling can get the right spot along that wave when it crests, they can actually sort of ride it like a surfer. So like if they're sort of in front of where that wave crest, it sort of pushes them forward and makes swimming a little more efficient. And they kind of pass it on to their brothers and sisters. So it's kind of a make way for duckling story, right?

Yeah, exactly. Yeah, exactly. Make way for ducklings. Well, that's all the time we have for now. I'd like to thank my guest, Sikhan Akpan, Health and Science Editor for WNYC Public Radio in New York. Thanks for joining us. Yep, thank you. We have to take a break, and when we come back, we'll talk about COVID-19 testing ahead of the holidays.

Are you wondering what kind of tests to take and when and how often? Stay with us. This is Science Friday. I'm Roxanne Camsey. Like a lot of people, I feel this holiday season really has snuck up on me. And like most holiday seasons, I've got logistics to figure out. It's tricky because there's a chance I might be flying internationally to see family. But of course, we're still in a pandemic, so questions of safety remain.

And at the end of the day, all of us want to keep our families, friends, and loved ones healthy. So how do we do it? COVID-19 tests are proving to be a popular tool for a lot of people to figure out whether a social situation is safe. quickly swabbing the nose or spitting in a tube can tell you if you have COVID. But with so many options and a big season of holiday get-togethers ahead of us, a lot of people are wondering what kind of test is best and when? The whole thing can become overwhelming pretty quickly. Joining me now to answer these questions are my guests,

Dr. Celine Gounder, epidemiologist, and professor at New York University's Grossman School of Medicine in New York City. Hi, Celine. Hey. And Dr. Alex Greeninger, Assistant Director of the Clinical Virology Laboratories at the University of Washington Medical Center in Seattle. Hi, Alex. Hi, how's it going? So, Alex, last year we were having a lot of the same conversations about how to have get-togethers safely. But a lot of things have changed since then, right? So can you walk us through what are the big differences between last year's holiday season and this one?

Well, I think the major differences between last year's holiday season and this year's holiday season. and this year's holiday season is the vaccines. We have the vaccines this year. So that's really by the most important things that changed. We also have some new testing modalities. So rapid tests were approved at the time, but many of them were not really available over the counter or could be bought easily by people.

So that's a new option. But we still have to use all of the different modalities we have to prevent transmission, it's masking, ventilation, and the whole pandemic playbook here. is really important. Yeah, I think those things are definitely big changes. And yet, as you mentioned, some of the stuff that we tried to do last year remains. Selene, how about you? Do you feel safe enough to get together with loved ones for the holidays? Well, I think there are a couple of questions I ask

myself and I think a good framework for people who are planning their holidays. I would say, number one, think about who's going to be there. Is anyone who's really vulnerable? So when I mean really vulnerable. I'm talking about the elderly, people with immunocompromising conditions. Maybe it's an elderly grandparent who lives in a nursing home. These are the people who are most likely to have a severe complication from COVID, even if they're vaccinated. They are at higher risk for a breakthrough infection that can progress on to severe COVID. So I really think you should be conscious of who's going to be there. And, you know, other people may have similar, but different issues where it's really too high risk for them to get an infection over the holidays.

So are you taking any special steps yourself to ensure that you and your family will be safe? Well, all of us, with the exception of my two-year-old niece, will be vaccinated. My six-year-old niece just got her first dose of the Pfizer vaccine. She'll get her second dose before the holidays. And my mom, who is elderly, has recently gotten her third dose of the most. Moderna vaccine. So we'll all be, with the exception of my two-year-old niece, will all be fully vaccinated before Christmas. But as Alex said, you know, you have to think about this as the full pandemic playbook of layering different things because none of them is perfectly 100% protective.

So in addition to getting vaccinated, you know, I do think rapid tests are probably the easiest thing to implement without disrupting your holiday activities. So yeah, so we're going to be layering, just like we layer our winter clothes, it's all about layering these different protective measures and then maybe throwing in some rapid tests too for good measure. Yeah, I think that's right. I love your metaphor of the winter layers. I think that's right. You know, like you have one layer that blocks out the rain. You have another that's warmer. I think that's a similar kind of thing here. So, Alex, let's talk about testing. You run a massive testing laboratory in Seattle. how many COVID-19 tests has your lab been processing? Yeah, so since the beginning of the pandemic, we've done about 3.6 million tests.

We were one of the first labs to go live, clinical labs in the country. And for us, that's about 72 years of testing in the last 20 months. That'll be across all analysts, but that's just for COVID. So it's really an incredible amount of testing that we've done. And those are the ones we know.

What's great, we get to do PCR testing. We can get high sensitivity. With those data get reported directly to public health, which is fantastic. And the new thing is basically these availability of these rapid tests, be able to provide that into household or at the workplace or many different other locations. I wish those tests were getting reported to public health as well. But they are, like we said in the layer, the different layers that can be used to prevent transmission and help people understand, you know, what their status is and how to interact with the healthcare environment as well. And just to note, so you're in an airport also as you're talking with us.

So you're probably thinking about the testing and action. as people are traveling, you're kind of getting a preview of the holiday season to come. Yeah, definitely. I mean, if you've been to an airport recently, I mean, it's almost back to 2019. Maybe like 20% lower. It's a little bit lower, but it's still, it's pretty hop in. There's a different attitude towards the virus. And I think a lot of people expect, you know, in the next, over the holidays, we're going to see a much higher rate of transmission, a lot more cases around the country, unfortunately. So, you know, one of the things that we're talking about here is the different test options, we have. And Alex, you were saying that you've been running millions and millions of tests,

which is phenomenal. But, you know, there's PCR, there's antibody tests. You know, some of these can take a few days to process and others are pretty instant. Would you recommend to listeners to have one type of testing over another for the holiday season? I mean, there's a lot to say for rapid tests because they give you that result at that moment, right? I mean, they're a hundred times less sensitive from an analyte standpoint, but the part that they're missing is maybe a little the less important overall from terms of, you know, where they're missing those infections or people who have lower viral loads, potentially a little less infectious. So there's a lot to say for different testing modalities, but I do like rapid testing from

the standpoint of you get the result right then and you know that status. So if you're about to go to a dinner party or you're about to interact with people, you know, the situation right then. You know, with PCR testing, the advantages are, it's usually collected and observed by someone else, it's run by someone else. You can use that results for many different purposes, whether it's travel or meets some of the OSHA requirements for workplace required testing that's helpful, as well as it gets reported to public health. And I think that's really important that our policymakers have a good understanding of how many tests are being done, how many infections are being picked up.

That's one of the most important things is the policy response that we have to the virus. So they're both helpful, but I do think from some of these holiday standpoint, it actually is, you know, rapid testing has a lot to offer as well. Roxanne, if I could add to that just briefly, I think the power of rapid testing is that it's rapid, but also that it's picking up the people who are really infectious or contagious to others. And so if the purpose here is really to reduce transmission, rapid tests are a really powerful tool.

It may not be what we want to use in the hospital when somebody is sick and we're trying to figure out what you have, but that's not really the purpose here. It's really just to figure out, are you contagious to? other people. And for that purpose, the rapid tests are really great tools. That's a lovely way to look at kind of the advantage of rapid tests. And I'm curious because in the past months of the pandemic, I have heard concerns that at-home testing isn't always as accurate. And so Alex, I'm wondering, do you have any thoughts on whether at-home testing is as accurate as what happens in the lab? I mean, they're accurate enough. They are, like I said, from an analyte standpoint, they are less

sensitive, but as Dr. Gander said, they are also picking up the, you know, people who are most likely to be infectious. I think what's most important to highlight when it comes to testing or any of this is the layers we talked about before, as well as what you do with the information and how you, how you act. I mean, I'm going to use the University of Washington football team from last year that basically did not get to go to the, to the Pact 12 championship game because they had an outbreak in a football team. They were getting daily antigen testing and weekly PCR testing. And yet the risk that they themselves were at, whether from their household transmission or from, you know, the team itself and the close quarters, you know, there are still 23 other hours during the day where you're not getting that results. And so while it's very helpful, you've got to as well sort of de-risk yourself and think about the other layers that you're bringing in if you want to, you know, avoid getting infection or having transmission. I mean, this is a lot to think about. And as we're talking, I'm also recalling that, you know, I was in an airport not that long ago.

and I tried to get access to a rapid test for travel and ordered one online, but by the time it had arrived, I was already on my flight. So I had to find other testing options. And I've heard that for a lot of people, finding rapid tests can be kind of a mixed bag. In some places, they're pretty accessible. And then other places, they're kind of impossible to find. Celine, do you have any thoughts on why supplies have fluctuated so much? I know you're not running the supply chains, but I'm curious if you have observed this kind of phenomenon. Yeah, I mean, I've certainly seen it firsthand, and there are a number of different bottlenecks. One, you have the FDA and their regulatory framework. They're not really set up to approve tests for a public health purpose as opposed to a diagnostic purpose. And when you're talking about testing to assess of somebody's contagious, not to make a diagnosis of COVID for their medical care, the purpose we're talking about here is really a public health purpose. And the FDA is not really set up to do that. In addition, they just weren't set up to approve this many new rapid diagnostic tests in the context of the pandemic.

There have been some moves recently from the White House to facilitate more rapid approval in the future. The NIH has recently announced a new program where they will, in fact, do a lot of the testing for the test kit developers. so there's a much more standardized streamlined process leading up to an FDA approval. But in addition to some of these regulatory issues, there have been, as you alluded to, there have been issues with the supply chain, so the different components that go into making a test, unlike in other countries like the UK, for example, where there was investment by the government pre-purchasing tests so that manufacturers knew there was going to be a certain demand, knowing that you have a predictable demand makes it a lot easier to ramp up supply.

I think there has been really bad messaging around how to use rapid tests. What's the purpose of rapid tests? I think everyone had really doubled down on vaccinations. And as we talked about earlier, vaccinations are really important. They might be our most powerful tool in the toolbox. But at least for the foreseeable future, we're going to need to layer other tools, other approaches. And then finally, I think what you alluded to at the beginning, which is it's really hard to find a test and they're really expensive. You know, you're still talking about, you know, easily $25 a test in many places.

For listeners, a couple places where you might look to for a lower price test would include iHealth Labs, iHealth,LABS.com. They currently are available at $7 a test. There are a couple different retailers, Walmart, Amazon, and Kroger, who have agreed. to sell their test at cost for $14 over the next three months. But many others, CBS, Walgreens and the like are also selling these rapid tests. It's just a question of can you get your hands on them? And as you're saying, these prices, I'm thinking maybe I'll make them stocking stuffers. Alex, can you say a little bit about what's the ideal time to do a COVID test ahead of, let's say, like, Thanksgiving,

which is coming up on Thursday? Right. So whatever test you're getting, the most important thing is that you're able to get that result and then act on it, whether it's antigen testing or PCR testing. So if it's PCR testing, you do have to factor in the turnaround time of the lab, which can be different in different locations. So, you know, generally, probably want to get tested probably on Tuesday, maybe Wednesday morning, depending different locations. And that's, that's one of the problems, right, is that there's still that time that can pass and you can still have the virus. For rapid testing, you know, if you're 15 minutes, you want to do it right before you go to dinner, where you're headed over to someone's place or whatnot, because you can get that result

and you can know immediate what your status is at that moment. And so that's really just want to make sure that you get the result with time and the ability to act on it. Otherwise, it's just you're just getting tested. Shelf life for them is quite long, right? So they'll be available for, you can get some now for Thanksgiving, you can get some now for Thanksgiving, you'll be stable during that entire time period. So you'll be, you'll be okay. It's not too late.

The worst thing would be to have like dessert and then get your result and find out that you're posited. Right. Exactly. Okay, great. Well, thanks for clarifying that. Just to pause here, I'm Roxanne Camsey, and this is Science Friday from WNYC Studios. We're talking about COVID testing ahead of the holidays with Dr. Celine Gounder and Dr. Alex Greninger. Celine, I know you have very strong thoughts about boosters. News came out today from the FDA. They've authorized COVID booster shots for all adults in the U.S.

The CDC still needs to sign off on it, but it's a really big step. And that's after several states have already recommended that residents get the booster. Celine, would you recommend that people get boosted now? So the people who should absolutely get boosted now are the elderly, and there's different ways of defining the elderly depending on the study. But definitely, if you are 65 and older, you should absolutely get a booster now. We know that that group, the elderly, has something we call immunosinensensis, which is basically aging of the immune system, where your immune system does not respond as well

up front to vaccination. So giving you an extra dose of the vaccine will help you generate a more robust, durable response to vaccination. The other groups that really would benefit from an extra dose of vaccine now are people who are highly immunocompromised. So, for example, somebody who's had a solid organ transplant. And then people who live in nursing homes. And this is really the setting in particular where we have seen people who have infections after vaccination, and those infections can turn bad. In other words, those people go on to severe disease, hospitalization, and death, unfortunately, not unfrequently. And so it's really important for people who are living in a nursing home, who work in a nursing home,

if you're planning to travel, to visit somebody in a nursing home, to also be more cautious. But the residents and staff of nursing homes and other long-term care facilities should absolutely receive another dose of vaccine now. So people in regular Thanksgiving settings where there's a mix of different generations, if people want to get boosted who might not be falling into those categories that you mentioned, if they want to get boosted to get the most protection for Thanksgiving, is it too late? If you're wanting to do that, I think you probably want to do that about two weeks prior to the holiday. And I think you have to be very clear about what it is you're achieving. I do think there's a danger that some people think that getting a booster,

means that now, you know, you don't have to worry about COVID anymore, you're Superman, you know, you're not ever going to have to take other precautions. And that is the danger here. By giving you an extra dose of vaccine, we know that will boost your antibody levels over the short term. We do not know what the impact will be on your underlying immune memory, which is really what you'll revert back to, fall back to within six months or so. And so I would just be very cautious about interpreting what that action means for you and for others. So a booster is not a free pass, and we should definitely continue to layer as we get through the holidays. That's right. That's right. Continue to layer.

We've run out of time. I'd like to thank my guests, Dr. Celine Gounder, epidemiologist and professor at New York University's Grossman School of Medicine in New York City, and Dr. Alex Greninger, assistant director of the Clinical Virology Laboratories at the University of Washington Medical Center in Seattle. Of course. Bye, everyone. Bye everyone. All right. Thanks a lot. I appreciate you all. Cheers. We have to take a break, and when we come back, we'll be talking about the Big Bang Theory of Cancer and how researchers are working to figure out exactly how cancer cells mutate. Stay with us. Hey there, podcast listeners. Last week, I shared that we're celebrating our 30th anniversary,

and I asked you to make a donation. I know I've mentioned this before, but it bears repeating. donations are crucial to Science Friday success. And right now we have a dollar for dollar match in effect, which means that any amount you give will be doubled. Yes, doubled. So please go to ScienceFriady.com slash support to make a donation. Again, that's sciencefriiday.com slash support. And thanks. This is Science Friday. I'm Roxanne Camseley in this week for Ira Flato. Cancer touches many of our lives, but there's still so much we don't understand. understand about it. One big question, how do tumors form in the first place? Researchers are getting closer to an answer. For years, the prevailing theory of tumor growth was that cancer cells

kind of gradually acquire a series of mutations that enable them to somehow out-compete our healthy cells and run amok. But improved genetic sequencing of cancers is revealing a much more complicated picture. From this technology comes a new theory of tumor development called the Big Bang theory, it turns out that some types of cancers contain a whole hodgepodge of mutations right from the very beginning, even before the tumors are detectable on a scan. To help us better grasp what this means for our understanding of cancer and how to treat it is Christina Curtis. She's an associate professor of medicine and genetics at Stanford University's School of Medicine. Welcome to Science Friday. Thanks for being here. It's my pleasure. Thanks for having me.

What's the prevailing model of how scientists understand tumor growth and the spread of cancer? How have we understood it in the past? So really the prevailing view is that cancer growth invariably follows the principles of evolution that Charles Darwin outlined for us in his theory of natural selection. And that theory was that organisms with favorable traits are more likely to reproduce pass their treats onto the next generation. And the way that was translated in the cancer field is that cancer cells that arise from our normal cells and accrue mutations can occasionally acquire a mutation that confers a really strong advantage for that cell to grow. And such that every time one of these beneficial mutations comes along, they will take over the population in effectively a linear or a stepwise fashion, gradually increase. the sort of aggressiveness of a tumor or its fitness. And so this notion was that it's very much stepwise, sequential over time. So how is the Big Bang model different from that?

Yes. So we were able to observe just this extensive diversity of mutations in cancers that suggested there wasn't one dominant event that took place that. that overtook or out-compete at all the other cells. And this led us to go back and really formulate an alternate model. And in this model, use the term Big Bang, because we postulate that early on, the nascent tumor acquires a full house of mutations that initiate that growth. And once it has those, it can expand rapidly,

creating a wealth of additional diversity, much of which are mutations that are passengers. They're non-consequential. They don't actually fuel the growth. They're just arising through the course of cell division. And so this really posits that there's a tipping point at which this cancer can expand rapidly, that it's not gradual or sequential, that much of the action happens really early on. So does this play in at all to why you called it the Big Bang theory? I mean, can you explain some of the parallels it has with this Big Bang theory of the creation of the entire universe? So we use that model because what we observed and what we observed really implies that we could go back and trace the origins of a cancer from what we detect in the clinic. So really, we don't know how the tumor became what it was, but the fact that we observed these very specific mutational patterns when we sequence,

tumor genome, suggested that this was really a reflection of how the tumor began. And so this parallels the notion that, you know, the cosmic microwave background is really a signature of the origins of our universe. And in both cases, these observations about the end product allowed us to reveal the origins of the universe and the origins of a tumor. A big part of your research is figuring out what happens before the cancer is even big enough to detect. But there's a catch-22 there. How did you use the samples from fully formed tumors to then go back retroactively and kind of chart their growth and find that big bang of tumor mutations? So we took, in this case, patients that had colon cancer, and we used sequencing technologies

that allow us to peer in and read out the genome sequence of our tumors. And in this manner, we really were able to do this at very high resolution using some advances in technology and assemble the patterns of diversity that we had observed. And what it really took then actually was computational approaches and some theory from other fields, from fields of population genetics, where we've studied the relationship between species to use that to trace back their ancestry. And you can kind of think of it that, you know, much as we can understand patterns of growth over time in a, you know, a tree, if we take a cross-sectional view,

concentric rings of the circle tell us about how that grew, we're able to look back in time and use the patterns of mutation to tell us about the origins of the tumor. And like how many mutations are we talking about in the colon? cancers that you looked at, was it like 20 mutations after the big bang of mutations or 100 or 2,000? Many mutations, many mutations. But I want to stress that a lot of those mutations that we observe, you know, in fact, mutations are happening all the time in our cells. And so these mutations are accruing our cells have many ways to cope with them. Most of them are inconsequential. They don't influence how the tumor will grow. And so there's many, many mutations. There's an

extensive diversity to the point that in fact every cell within a tumor may be genetically distinct. And that poses real challenges for how we might treat patients and poses risks to the development of resistance to our very best therapies. And like, I know you looked at colon cancer, but are there other types of cancers that follow this Big Bang model? Like, for example, in the liver or stomach? and do we know why some types of cancers follow the Big Bang model? Yeah, so there's been some surveys to really try to understand how different tumors evolve. And I would say this is sparked, you know, really reinvigorated the field and how we think about this.

And you're correct. There's a whole host of tumors of the gastrointestinal tract. We can think of liver, not only colon, the stomach, as well. is even pancreas that tend to follow this model where growth is rapid, expansion is rapid, and the diversity is vast. Now, why that's the case, particularly in gastrointestinal cancers, is still unknown, but we would speculate that it may have to do with the organ structure and the architecture within that is innate to our different organs. I mean, that's so, interesting to me that you're finding that this is the case for some cancers, but that not all cancers

have this big bang phenomenon operating in them. It also makes me wonder, do we know what causes a cancerous cell mutation in the first place? So mutations accrue at random. That happens throughout the lifespan. And of course, we have many trillions of cells in our bodies. So we are constantly coping with these insults. Now, some of these mutations affect proteins that carry out critical functions in our cells. And sometimes those mutations can cause a growth advantage for a cell. And that is really what we think of as the key drivers of tumor growth. Now, we believe, and much work has suggested that there's probably a limited set of events that actually initiate a cancer, that form a cancer. They differ by our tissue types or organ types. And yet, there's not so many

of them. But the cell must have accrued a particular constellation of these events. It's very seldom that a single event is going to cause a cancer. So they clearly have a genetic origin. And there seems to be some preference in different tissue types for particular mutations, meaning that they, they promote growth in one environment, but not in another. I'm wondering, as you're talking, you know, once a tumor is fully formed, does it still continue to evolve over time? Absolutely. So that is one of the greatest challenges that we really face is that tumors are constantly evolving. They're not static. This is a highly dynamic process. And what that means is that given this diversity, given the vast array of mutations that a tumor can have, that we need to anticipate whether or not any of those mutations can confer or allow for resistance to therapy, because we're really dealing with a very large population.

So there's a huge amount of variation to be acted upon by evolution. and that is a key, key challenge for the field. Knowing about this Big Bang theory, how does that help scientists point doctors towards better cancer treatments? So while those mutations that we've talked about may not fuel the growth of the tumor, they may enable resistance to a particular therapy.

And there's such diversity that there's really this huge reservoir of ways in which are, a tumor can evade therapy. And so that's a problem. We need to really anticipate resistance. And we need to harness the evolution therapeutically, meaning can we exploit this variation to actually impede cancer growth? And that's really a very active area of ongoing research. So how would you do that? So you're saying you could leverage the fact that there's this big bang of mutations to somehow undermine the way the cancer can grow? You know, a particular mutation may confer resistance to one drug, but possibly sensitivity to another or that there's a tradeoff in the fitness of that cell that could be exploited.

And so we need to clearly do much more research to know the many ways we can exploit this because each patient's tumor is distinct. But arguably our best tools to tackle this ongoing evolution is the evolution itself and to design evolutionary grounded therapies. So it sounds like there's a really complex conundrum there for doctors to pick the right treatment, but that somehow looking at all the mutations might guide us towards these things where we can be more nuanced about how to treat the tumor. One thing I did wonder is about metastasis. So the idea of a tumor that's kind of able to spread in the body, does the Big Bang theory inform our understanding of how cancers spread in the body? What we've been able to do this on sort of an initial basis. And what we're finding is really quite profound.

And for example, when we compare these patterns of diversity between the originating tumor and its metastasis, which is really the cause of patient death, what we tend to find is that there's really strong evidence that these tumors can, leave home early. And by leave home, I mean leave the primary organ site and disseminate and colonize another organ. And so that comes back to really the early origins of tumor formation. And the notion that, in fact, what we had posited alongside this theory was that some tumors may be born to be bad, that their aggressive potential is specified really early, that it's dictated by these early mutations. and that has been borne out in a number of studies, both from our work and from others.

And of course, that gives us quite a bit of pause because, again, it really highlights the fact that this process is not necessarily gradual as it has long been assumed. And it places considerable emphasis on earlier detection. I'm Roxanne Kamsley, and this is Science Friday from WNYC Studios. So it sounds like metastasis is something that happen really early in a cancer development, which does point towards the value of early detection.

But as you kind of hinted to earlier, there's different kinds of cancers that may or may not follow this Big Bang model. Some of the mutated cells, as you mentioned, might be born to be bad. And you've got some current research on breast cancer that has some promising new insights into why some types of breast cancers return after, let's say, five or ten, or even 20 years of remission. Can you tell us a little bit about what you found there? So really using very different approaches, what we observed is that there are specific genomic differences amongst breast cancer patients, some of which had not been previously appreciated. And so really, we can classify breast cancer into some 11 subgroups. So that's a lot. But these groups really have distinct

mutational landscapes, distinct features. And remarkably, some of these genomic alterations allow us to predict which patients are likely to relapse from their disease. And in some cases, up to two decades after that initial diagnosis. So really, again, as we saw in these earlier studies in colon cancer and has been extended to other tumor types, specific genomic alterations can provide a wealth of information about what that tumor's trajectory may be and allow us to forecast its next steps. So you're doing a lot of looking back at tumor histories with genetic sequences and also kind of using that insight into the mutations to look forward and maybe give us a better sense of what's to come. That's right. We think that

if we can understand the origins of a cancer, that it really provides fundamental clues as to how to better detect those cancers to intercept and then to treat them in a far more personalized manner. And so it really is quite nuanced, given the heterogeneity. But equally, there are some core principles here that I think really give us some hope that we might be able to understand what those alterations, those mutations are, and to go after them. So there is, some, you know, silver lining there in terms of how we can use this information to improve patient outcomes. Well, that's a great positive note. And I think that looking forward in that way sounds fantastic. I'd like to thank my guest, Christina Curtis, Associate Professor of Medicine

and Genetics at Stanford University's School of Medicine. Thanks so much, Christina, for joining today. Thank you. That's all the time for today. Here's Diana Monta. with some of the people who made this show possible. Christy Taylor, Kathleen Davis, and Shoshana Buxbaum are our radio producers. Daniel Peters Schmidt and Lauren Young are our digital producers. Andy Nero is our individual giving manager, and I'm Diana Montana, Outreach Manager. Thanks for listening. Thanks, Diana.

BJ Leatherman composed our theme music. And on the Science Friday Vox Pop app, we'll soon be speaking to Ralph Nader, about the 55th anniversary of his groundbreaking. book, unsafe at any speed. That book sparked major change for auto safety in the U.S. Do you have questions for Ralph Nader about consumer safety in our new age of technology? Let us know. That's on the SciFry Voxpop app, wherever you get your apps. Have a great weekend. Ira will be back next week. I'm Roxanne Camsey.