Öйú365betÖÐÎĹÙÍø

Over the last 200 years or so, vaccines have come a long way, for a number of viruses. We’ve made so much progress, in fact, that in 2017 scientists began the early stages of vaccine development for some virus families they believed could pose a future pandemic threat. One of those families was Coronaviridae: coronaviruses. Not many people know that before SARS-CoV-2 started making its way into people in 2019, there was already a project underway in the U.S. to create a vaccine for a looming coronavirus (we didn't!), but even that would not have been possible without the decades of vaccine and drug research that came before it, particularly for HIV.Ìý

Transcript of this Episode

Deboki: In May, 1796, an 8-year-old English boy named James Phipps made history, becoming the first person in the world to be vaccinated for smallpox. James was inoculated by English physician Edward Jenner, who used fluid from a cowpox sore that had been retrieved from the hand of a milkmaid. Cowpox and smallpox are caused by viruses in the same family, but they’reÌý quite different in terms of severity. Cowpox is much milder and not as contagious. Smallpox, by comparison, is very dangerous with around a 30% fatality rate.Ìý

Sam: Phipps made a full recovery and then, two months later, was challenged with the goop from a human smallpox sore. Risky? Absolutely. But Phipps was fine, he never developed smallpox. And now scientists were seeing that people could become immune to a disease without actually being exposed to the material that causes it. Jenner referred to cowpox as “variolae vaccinae,â€� Latin for “smallpox of the cow.â€� Ultimately, “vaccinaeâ€� gave rise to “vaccineâ€�.Ìý

Over the last 200 years or so, vaccines have come a long way, for a number of viruses. For one, we no longer have to inoculate people with pus. We’ve made so much progress, in fact, that in 2017 scientists began the early stages of vaccine development for some virus families they believed could pose a future pandemic threat. One of those families was Coronaviridae: coronaviruses.Ìý

Deboki: Not many people know that before SARS-CoV-2 started making its way into people in 2019, there was already a project underway in the U.S. to create a vaccine for a looming coronavirus. But even that would not have been possible without the decades of vaccine and drug research that came before it, particularly for HIV.Ìý

Welcome to Tiny Matters, a science podcast about the little things that have a big impact on our society, past and present. I’m Deboki Chakravarti and I’m joined by my cohost Sam Jones.Ìý

Sam: Deboki, this is a story that I find so compelling. Because at its heart it is about science and society at their best in an incredibly challenging time.Ìý

When we started hearing that a vaccine trial was already underway less than a month after the World Health Organization declared COVID-19 a pandemic, it was exciting but also confusing…How could things move this quickly? Didn’t vaccines take forever? Was that possible while also being safe? What the heck was an mRNA vaccine? A lot of details were omitted or lost in the deluge of information that we had coming at us.Ìý

But the more I talked with the guests you’ll hear from today the more I learned that, yes, things moved quickly, but they were only able to move that fast because of decades of work � not only on other coronaviruses but respiratory syncytial virus or RSV, and Zika, and Nipah virus and, I’d argue most importantly, HIV. This is a story that is so much more interesting and complicated than I imagined and it sheds light on how we went from identifying a new virus to a vaccine in just 11 months.

Deboki: Sam I am so ready for this. Let’s get into it.

Barney Graham: Viruses are fascinating microbes or little entities that carry genetic information, create disease, evade immunity. They are a part of human evolution. Once you start learning more about viruses and learning not only how they contribute to biology, but how then they cause disease, and learning there are ways that each virus causes disease, and learning unique ways of preventing that disease, that's a whole lifetime's worth of things to figure out.

Deboki: That’s physician-scientist Barney Graham, a professor of medicine and microbiology, biochemistry and immunology at Morehouse School of Medicine in Atlanta, Georgia where he is also the founding director of the David Satcher Global Health Equity Institute. Before that he had spent 21 years as deputy director of the Vaccine Research Center at the National Institutes of Health and led the team that developed what became the Moderna COVID-19 vaccine.Ìý

Barney Graham: I grew up in eastern Kansas in small towns and spent my teenage years in farming. We raised pigs and horses and cattle and farmed a lot of crops and I learned a lot of biology during that time.

Deboki: While in medical school, Barney took a research sabbatical, spending nine months in a lab studying a virus that could transform normal muscle cells into rhabdomyosarcoma cells. Rhabdomyosarcoma is a rare and aggressive cancer that develops in skeletal muscle and other soft tissues. It was Barney’s first exposure to virus research, and he was hooked.Ìý

Barney Graham: I went to Vanderbilt for residency training after medical school. And as things progressed, I was chief resident at General Hospital in Nashville in 1982. I saw the first patient diagnosed with AIDS in General Hospital in 1982. And that event and the emergence of this new disease that was untreatable at the time was very compelling. When you see things like that during training, it's hard to turn away.

Sam: So let’s fast forward to 2002. Shortly after Barney arrived at the Vaccine Research Center at the NIH, there was the first SARS outbreak. In the fall of 2002, SARS or severe acute respiratory syndrome popped up in the Guangdong Province in China, ultimately spreading to 29 countries with a reported 8,422 cases and 916 deaths.Ìý

Barney Graham: But we didn't really know much about coronavirus. We didn't have a structure of the spike protein, we didn't have Zoom, we didn't have a lot of things that made this new context so different than the original context.Ìý

Sam: Unknown to Barney and everyone else at the time, the work he was doing at the NIH’s Vaccine Research Center that focused on HIV would end up being essential for what was to come.Ìý

Barney Graham: The threads of this story include all the technologies that were developed by trying to make an HIV vaccine.

Deboki: Those technologies were wide ranging. For example, scientists learned how to identify the structure of a virus, which was no easy task. It’s also really important because it helps scientists find antigens, which are proteins that stick off of a virus, and that your immune system detects. So being able to find antigens helps us design treatments that can effectively trigger an immune response. Scientists also learned how to rapidly sequence the genome of a virus.

Back in the early 2000s, all of these technologies were being developed primarily with the hope of creating a vaccine for HIV, but they also quickly became applicable to other viruses, like RSV. For instance, in 2008, Barney began working with researcher Jason McLellan to work out the structure of RSV. It took a few years, but once they had it, they immediately knew they could make a much more effective RSV vaccine than the one on the market.Ìý

Barney Graham: Finding that structure of RSV in 2012 and publishing in 2013 is what’s led to the current RSV vaccines that have been licensed in the last two years. So RSV really told us that there are generalizable principles that can allow you to make vaccines within viral families or maybe even across viral families.

Sam: The same year that Barney, Jason, and their colleagues identified the structure of RSV, there was another coronavirus outbreak. This time it was Middle East Respiratory Syndrome or MERS, which began in Saudi Arabia in April 2012. So Barney and Jason decided to take what they’d learned from HIV and RSV to try to understand this new virus.Ìý

Barney Graham: And it was complicated and difficult. The MERS and the original SARS were unstable spike proteins. We couldn't get structures of those, but finally turned to an endemic coronavirus called HKU1.ÌýÌý

Deboki: Human coronavirus HKU1 was first identified in Hong Kong in 2005. It typically causes an upper respiratory infection and cold-like symptoms but it can progress to pneumonia. It’s one of a number of common human coronaviruses that circulate each year. You don’t want to get sick with any virus, but HKU1 is nowhere near as dangerous as SARS-CoV-2. Soon, Barney and his colleagues had worked out the structure of HKU1’s spike protein, which helps the virus get into cells.

Sam with Barney: What was it comparatively that made the other forms so unstable versus the one that you could figure out the spike protein for?

Barney Graham: I think as viruses first come into human populations, they're not adapted to humans yet. So whatever the characteristics are of those spike proteins that help viruses enter cells, there's adaptation over time that mostly to help the virus become better able to replicate in human cells and partly to help the virus transmit.Ìý

Deboki: So SARS-CoV-2 began as a virus that had a pretty unstable spike protein. It initially grew best at 37 degrees Celsius � 98.6 Fahrenheit � down in the lungs. But, as we now know, it quickly mutated.

Barney Graham: Over time, the virus has adapted to grow better at 32 degrees up in your nose, which makes it obviously easier to transmit, and it's learned to grow faster in human cells. So that's why instead of a three or four or five day incubation period, it's more like a one or two or three day incubation period. So the virus has adapted, a lot of that adaptation has happened in spike protein.Ìý

Deboki: The HKU1 virus, in comparison, had been circulating in humans for so many years that its spike protein was quite stable, meaning it was much easier to get the structure.Ìý

Sam: OK, so, this is 2016. Given how technology was progressing, Barney and his colleagues were also working on a proposal that would help scientists be as ready as possible for any pandemic-causing virus that might come our way. There are more than a hundred families of viruses, 26 of which are known to infect people, including coronaviruses, herpes viruses, and pox viruses. What they proposed was studying a prototypical virus within each of those 26 human-infecting families so that they could have as much information as possible about its proteins and other characteristics.

Barney Graham: So that was a proposal around the time we got the structure of the HKU1 spike protein that we published that year. And then we started a project with Moderna in 2017, and the project was to do the prototype pathogen with paramyxoviruses and with coronaviruses, those two viral families, we wanted to have a demonstration project that we could do this quickly if we needed to.

Deboki: Their reason for turning to the pharma company Moderna, a name you likely know well by this point, was because they had worked with them in 2016 to develop a messenger RNA or mRNA vaccine for Zika virus that was doing really well in trials. mRNA was looking very promising compared to, say, a conjugate vaccine, which uses protein, or a live attenuated vaccine, which uses a weakened, living form of the virus.Ìý

Sam with Barney: When people ask you, how does this work, how is it different from a live attenuated or inactivated vaccine, what do you say? How is an mRNA vaccine different?

Barney Graham: Well, what I usually say is that every living cell on earth, whether it's an animal or a plant or anything, has RNA in it. Every living thing has RNA everywhere. And so RNA as a vaccine is to me the simplest, fastest, I can say most elemental way of delivering a vaccine antigen as a protein. Keeping a vaccine simple means you're keeping them safe and using things like RNA that is gone within hours after you've injected it, it never goes into the nucleus like DNA does. It only goes into the cytoplasm. It makes its protein and it is degraded by the cell. It's gone.Ìý

Deboki: So just to reiterate, an mRNA vaccine doesn’t go into the cell’s nucleus where your genetic information lives bundled up in chromosomes. It stays in the cytoplasm and then gets broken down.

Barney Graham: And so the RNA is the simplest, easiest way of creating an immunological lesson for your immune system without any of the other parts of the virus.Ìý

Deboki: Alright, so back to the prototype project that began in 2017. For the first prototype â€� the paramyxovirus prototype â€� Barney and his colleagues chose nipah virus, a respiratory virus that can lead to encephalitis with a 40 to 75% fatality rate. For the coronavirus prototype, they went after MERS. And by 2019, they knew how to make viral antigens for both MERS and nipah virus. At the end of that year, their plan was to start with nipah virus and make mRNA coding for that antigen, to hopefully be used in a vaccine down the line.Ìý

Barney Graham: So we had all these different threads in place when, on the 31st of December, we heard about this new virus circulating in China. And by the 6th of January, we heard a rumor that it was probably a beta coronavirus. And so that night, Stéphane Bancel, the CEO of Moderna, and I talked and said, let's switch our demonstration project from paramyxoviruses to coronaviruses because it just makes it more relevant, makes it seem more real. It wasn't a pandemic at that point.Ìý

We said, as soon as we see the sequences, we will put in the mutations we think will make it a better vaccine antigen and give you a sequence, and then we want the RNA back as fast as you can. We will solve the structure, make the assays, infect the mice, and do everything as fast as we can, and then show people how this prototype pathogen approach can work if needed. We were not really responding to a pandemic. And so we had a plan. We didn't at that time know the stakes were quite so high.Ìý

Deboki: Fortunately, on January 10th, 2020, the SARS-CoV-2 genetic sequence was released by the Chinese Center for Disease Control and Prevention, and Barney and his team had something to work with. They were off to the races.Ìý

Sam with Barney: You went into this thinking, this is going to be a development project, not that you were going to be trying to create a vaccine to treat the masses as soon as you possibly could. So I'm wondering, if you go back to that time, I'm wondering how you were feeling when you saw…this is a pandemic. This is being declared a global pandemic.

Barney Graham: Well, by the end of January, beginning of February, there were now cases in the U.S. There were stories coming out of church choir practices infecting 80 people at a time, making it obvious that there was aerosol spread, that it was quite contagious and that it was a real problem. So by the end of February, or really the beginning of February through February, we knew that this was no longer a demonstration project, this was the real thing.

Deboki: By February 4th, Barney and the team had RNA back from Moderna. They injected it into lab mice the same day. Two weeks later, they had promising immunology data back and gave the mice their second dose.

Across the world, physician-scientist Chris Beyrer was giving a plenary on the state of the HIV epidemic at a meeting in South Africa.Ìý

Sam: Chris is an epidemiologist and the director of the Duke Global Health Institute. Epidemiologists study the cause and spread of disease at the population level, looking for trends and patterns that could help with disease control. But all anyone seemed to want to talk about at this HIV meeting was SARS-CoV-2. At the airport on the way back, Chris bumped into a colleague�

Chris Beyrer: And she said, I have to show you something.Ìý

Sam: Chris remembers her opening up a figure on an iPad that modeled SARS-COV-2’s reproductive rate â€� how contagious it would be â€� compared to all of the pandemics going back to the incredibly deadly 1918 influenza pandemic caused by H1N1.Ìý

Chris Beyrer: And so there was measles and there was bird flu, and there was swine flu, and there were just a whole bunch of these curves. And the only curve that was approaching the great influenza of 1918 was SARS-CoV-2.

And we both just sort of sat there� oh my, wow, that is incredible. And she said, yeah, I think we are in for a really severe global pandemic, and it is accelerating right now. So I just made it home. I got home March 1st of that year, and then very shortly thereafter, the world started to really shut down.

Sam: Much like Barney, Chris’s drive to do virology research began many decades before, intensifying during the HIV/AIDS epidemic.Ìý

Chris Beyrer: I went to medical school in New York City in Brooklyn in the 1980s, and it was absolutely the emergence, and for some of those years, the height of the HIV/AIDS pandemic, but specifically in New York City and specifically in East Flatbush, Brooklyn, where we had many, many communities that were affected.

And of course, you have to remember at the time that there was no effective therapy, so we couldn't really treat these patients, and we didn't know until 1985 � it was my sophomore year � when a test was developed, that there was such a thing as asymptomatic infection. And all of a sudden, when we knew that and we started doing widespread testing, we realized that for every patient we had in the hospital, there were 10 or more out in the community who were going to be in the hospital sooner or later, but were living lives and were of course very much at risk for the disease AIDS as opposed to just HIV infection. So that was an extraordinary, powerful, painful, intense experience.

Deboki: Chris went on to do a preventive medicine public health residency at Johns Hopkins.Ìý

Chris Beyrer: And in that time I was very fortunate that really one of the great vaccinologists at the time was a woman named Mary Lou Clements, and she was my advisor, and she really convinced me that the search for an HIV vaccine was going to be essential to addressing the HIV epidemic.

I finished my training in 1992 and immediately my first job out of training was to set up HIV vaccine trial sites and do the epidemiology and molecular epidemiology around this very hot HIV epidemic in northern Thailand. So I finished my training and I moved to Thailand in 1992, and I spent the next five years there working on HIV epidemiology prevention vaccines in Southeast Asia.

Deboki: Over the last 30-plus years there has been, and continues to be, a search for an HIV vaccine, there are even trials happening as we speak. But there have been a number of other treatments that have been developed in the meantime.Ìý

In 1996, the first effective HIV therapy, a drug cocktail called Highly Active Antiretroviral Therapy, was introduced, saving countless lives. But as therapies became available and improved, they were often limited to wealthier nations.

Chris Beyrer: So I got very involved in the work toward access and equity in global health. And I think that what we eventually achieved, which was getting close to 75% of all people living with HIV worldwide access to antiviral therapy is one of the great achievements in global health. And so I really spent the last 20 odd years really very heavily focused in that area.

Sam: So, going back to the beginning of March, 2020. Chris had recently returned from South Africa after that alarming conversation with a colleague in the airport. And soon, he’s invited to a Zoom call with about 400 investigators, including other epidemiologists, vaccinologists, and immunologists. Tony Fauci, who was, at the time, director of the National Institute of Allergy and Infectious Diseases, was announcing that COVID-19 vaccine efficacy trials were starting.Ìý

Chris Beyrer: There were going to be five trials, each one starting over successive months in the next six months with 30,000 people each. So we're going to need 150,000 American volunteers to do these trials and that we were going to use the platform that had been built for HIV vaccines to mount the COVID vaccines.

Sam: But it wasn’t just COVID vaccines that were being tested, there were also antiviral drugs and antibodies.

Chris Beyrer: The reason we were able to stand up trials of three different classes of agents � vaccines, antiviral drugs, and broadly neutralizing antibodies � is because that infrastructure had been built for HIV.

Sam: There were three HIV networks that became platforms for COVID-19. One was the AIDS Clinical Trial Group or ATCG, which hosted the trials that eventually led to successful therapy for HIV infection. That network pivoted to do the antiviral trials for COVID infection. Then the HIV Vaccine Trials Network or HVTN became the platform for the COVID vaccine trials. And the HIV Prevention Trial Network, the HPTN, which helped in the development of pre-exposure prophylaxis or PrEP to prevent HIV, was already working on broadly neutralizing antibodies or bNAbs for a number of diseases.Ìý

Broadly neutralizing antibodies can reduce a virus’s ability to infect and replicate in your cells.

Chris Beyrer: And that's extremely important because, for example, if people are very elderly or frail, they may not mount much of an immune response to a vaccine.Ìý

Deboki: And beyond treatment and prevention, these networks have been working in their communities for years, which was so important for tackling COVID-19. They all had community advisory boards for trial sites that had long been established. It was the only way they could pivot from HIV to COVID-19 and gain the trust and participation of communities.

Chris Beyrer: And I will say that the whole idea of community advisory boards and of the participation of people affected by a pandemic comes out of HIV. It comes out of, not out of science. This is not one the science or the government can claim. This came out of activism, literally showing up at the NIH and the CDC and the FDA and banging on the doors and saying, look, we are the people dying. We want a seat at this table. And they demanded it, and they got it. And that has transformed science.

Deboki: And, Chris said, scientists like Barney, who see the importance in respecting and partnering with communities are the ones who have the biggest impact.Ìý

Chris Beyrer: Barney Graham is a great example of somebody who worked very closely with the faith community and with African-American community organizations, groups, and really, really has just a huge heart for community that comes out of years of work in HIV.

Sam: The first phase one clinical trial of the COVID vaccine began on March 16th, 2020. Barney told us his daughter was one of the people in that first trial. And although we’re spotlighting Barney in this episode, he made a point to talk about a star postdoc in his lab at the time, without whom this wouldn’t have been possible. Her name is Kizzmekia Corbett-Helaire.

Barney Graham: She was a young woman helping to do all this coronavirus work over those six or seven years between 2014 and 2020, working out the animal studies, the assays, et cetera. And so she and a team of three other African-American students did almost all the lab work that was needed between the 10th of January and the 16th of March in order to get that first phase one trial launched.

And the other students were, they were between college and graduate school or college and medical school. So they were relatively young, somewhat experienced because they'd been in the lab for a while, but they were students in the lab with Dr. Corbett and in our lab doing most of this work for people who didn't even know they were doing the work, to get this vaccine ready and the data needed to support the vaccine ready so quickly in order to launch those phase one trials in March. And so I think some of the young people who do a lot of the hands-on work at the bench to make proteins and all that, sometimes get lost in these stories.

Deboki: Kizzmekia now leads her own research lab at the Harvard T.H. Chan School of Public Health, and her lab continues to work on vaccine development for pandemic preparedness.Ìý

Sam with Barney: So the vaccine that you all worked on, the Moderna one, it became available in December, 2020. A lot of people, of course, have argued that that's rapid development. In some ways it is. It was very fast. But did it feel like rapid development to you?

Barney Graham: Yes, it did. Okay. I mean, we were pressing. I told Dr. Fauci at the beginning that everybody wanted a vaccine immediately. And I said, it's going to take at least 12 to 18 months, even if everything goes perfectly. So everything was fast. Nobody let paper sit on their desk overnight. And we really tried to be strategic at getting rid of all the gaps in between steps, and everybody was working together to try to facilitate the process. But I can tell you that no steps were skipped. And in my opinion, I've been doing this vaccine development work since the eighties, and I've never seen a vaccine with this much data. I mean, I think there were almost 500,000 papers written during the couple of years around the pandemic on coronaviruses. My little RSV virus that I'd worked on my whole life, the whole literature of RSV is only about 22 or 23,000 papers. So there was a lot of work on coronavirus in a very short amount of time, partly because of all the work leading up to that that had been done over these last four decades on how to make an HIV vaccine and how to advance some of these new technologies. So it was rapid, but we enrolled almost 200,000 people in three or four months and had a lot of safety testing.Ìý

Deboki: On December 18, 2020, the Moderna COVID-19 vaccine received emergency use authorization from the FDA. It’s estimated that the COVID vaccines, including the Pfizer vaccine and others, prevented 19.8 million deaths, about a 63% decrease in total deaths during just the first year of COVIDâ€�19 vaccination.Ìý

Sam: In the early Spring of 2021, I still have the most vivid memory of driving with a friend to a vaccination site a couple hours away. I was truly on the verge of happy tears as soon as that first shot went into my arm and, 14 days later, when I went for my second and final shot, the relief was palpable. This is an incredible science and societal success story, and one built on decades of discovery, disappointment, and resilience. The tenacious scientists, activists, patients and volunteers, not just for COVID-19 but HIV and RSV and Zika, and even eight year old James Phipps 224 years ago, really made all of it possible.

Deboki: Should we Tiny Show and Tell now?

Sam: I think we should.

Deboki: All righty.

Sam: I can go first this time. Okay. Deboki, I'm going to tell you about how lemurs are bullies. At least the female lemurs are. So�

Deboki: Cool. Great.

Sam: Yeah, so apparently they can be very aggressive, particularly toward males, and it can be totally unprovoked simply to remind them of who's in charge, which...

Deboki: Yeah. Yeah. Is it unprovoked?

Sam: I'm, like, I kind of respect that, but... And I would've had no idea that so many lemur species were aggressive. I'm, like, they're just so cute and sweet.

Deboki: Yeah. Did you watch Zoboomafoo growing up?

Sam: No.

Deboki: Okay. So this was an animal show, I think on PBS. And so it was, like, the Kratts brothers, and I think they had a lemur, and I think...I think it was a lemur. I think Zoboomafoo is a lemur, and I don't know, that's just immediately where I went to because now I'm picturing this aggressive bully lemur coming in and being like actually...

Sam: Well, and I'll tell you, it gets more complicated than that. It's not all female lemurs. So it seems like in one branch of the lemur family tree, some species have evolved over the last million years and the sexes seem to get along a whole lot better. And now the shift after this current research that came out, it seems to have to do with oxytocin, which is a hormone that's involved in trust and bonding and other social behaviors. And we have an episode on oxytocin. Go listen to it if you want to know more about that hormone.

But essentially what happened was Duke University researchers studied seven closely related lemur species in the genus Eulemur, I think. E-U-L-E-M-U-R. So some of those species have these domineering females and some are more egalitarian. So to do this study, they actually used frozen brain tissue samples from lemurs who had died of natural causes at the Duke Lemur Center. So oftentimes when you see lemur research coming out, it's out of the Duke Lemur Center because they have this big, really nice lemur center there.

But yeah, these animals had died, then their brains had been taken and frozen so that they can go in and look for different things. So in this case, what they did is they used an imaging technique called autoradiography to look at binding sites for oxytocin in the brain. And what they found was that these evolved, egalitarian species of lemur had more oxytocin receptors than the other species where you had these domineering females. And so what that means is you have more places for oxytocin to bind. And they didn't just see this in females, they saw it in the males too, which I thought was really interesting.

Deboki: Huh.

Sam: And so, one of the researchers said, this suggests that gender or sex equality where females became less aggressive toward the males, you'd wonder if, is it just that the males have ramped up their aggression too? So now it's like everybody's just kind of on a similar playing field?

Deboki: Yeah. Yeah.

Sam: But it seems like that's not the case. It seems like you're getting more oxytocin binding in the brain, and so these males and females are kind of matching each other. I thought that was fascinating. And it does depend on the species. So this very cute lemur that you mentioned that I don't remember the name of.

Deboki: Zoboomafoo.

Sam: I wonder what species of lemur, because there are a number that are actually...

Deboki: So I� Wikipedia does include this important detail. Zoboomafoo was a Coquerel's Sifaka lemur. It's in the Sifaka genus.

Sam: Oh. Okay. Interesting. Well, they didn't look into that genus.

Deboki: So we don't know. We don't know.

Sam: So I don't know.

Deboki: It does seem they have a particularly pronounced matriarchy system.

Sam: Oh, I bet the females are kind of mean.

Deboki: Yeah. All adult, and even most sub-adult females, are dominant over males according to Wikipedia.

Sam: Yep. There you go.

Deboki: A female may choose to mate with only one male, but most often she mates with several.

Sam: She does what she wants.

Deboki: Yeah. Sorry, now I'm just fully like I got to go watch the Zoboomafoo with new eyes. Well, thank you, Sam. That was really interesting. I have a story from the New York Times. This is more, again, of a longer article recommendation. So it's about a conservation effort particularly focusing on Maryland because Maryland has just been really successful at this. So the effort is called 30 by 30. The goal, kind of, globally is to protect 30% of land and water on earth by 2030. And so there are a number of States that have committed to this, and Maryland has succeeded in its effort, making it six years ahead of schedule. It's not 2030 yet, but they're there.

They have permanently protected 1.9 million acres of land. So they've been so successful that they're now trying to continue pushing this forward to conserve 40% of land by 2040. And so this article explores why they were able to do this, what some of the policy and social factors were. There's a program since the '60s in Maryland called Program Open Space where the State can get green spaces from voluntary sellers or these easements where basically the owners can still work the land, but they also agree that the land will never be developed even if that ownership gets transferred over to someone else. Conservation also has bipartisan support in Maryland, so that's an important factor. So I just thought this was a really, kind of, exciting and interesting article. I think it's really, I don't know, it kind of reminds me a little bit of our episode today, about these long-term efforts and about how it involves so many people to make these things happen. And it can be tough and frustrating at times, but there's always some kind of promise there too, if we can keep things going.

Sam: Yeah. Yeah, it's hopeful.

Deboki: Yeah, exactly. Thanks for tuning in to this week’s episode of Tiny Matters, a podcast brought to you by the American Chemical Öйú365betÖÐÎĹÙÍø and produced by Multitude. This week’s script was written by Sam, who is also our executive producer, and edited by me and by Michael David. It was fact-checked by Michelle Boucher. Our audio editor was Mischa Stanton.

Sam: Thanks so much to Barney Graham and Chris Beyrer for joining us. Go rate and review us wherever you listen, we super duper appreciate it. We’ll see you next time.

References:

• Ìý
• ÌýÌý
• Ìý
• Ìý