From dogs to fruitflies we've sent all sorts of animals to space. Some were sent up during the early space race to see if anyone could survive the journey, others are aboard the international space station right revealing how space flight affects life itself. While some of these non-human astronauts may have lived to walk on earth again, many are not alive today because of their missions. So, to show our appreciation for all these animals and what they've taught us, here's a video celebrating their accompli. Let's start by letting Kaitlyn address the elephant in the room: "Why would we want to send animals to space in the first place?" In 1961, cosmonaut, Yuri Gagarin became the first person in space. Since then more than 500 people have left Earth's atmosphere and 12 people have set foot on the Moon. But back when space travel was still very new, we didn't know whether life could survive in space. So scientists had to come up with ways to find out, and for decades they've been studying life in space with the help of some crawly, wiggly, fluttery, furry friends. These experiments were vital for helping scientists develop the grand new technology that we needed to take our first steps off of Earth. And since then, they've helped scientists study the effects of long term space travel on living creatures. The idea of using the animals to test flights goes back a really long time. The Montgolfier Brothers had a duck, a sheep and a rooster as the first passengers to ride in a hot air balloon in 1783. They wanted to test the effects of high altitude on live animals. The sheep was a stand in for a human, while the duck, thanks to its ability to fly, was considered a control. It would be a long time before we got to send anything beyond our atmosphere though. After several launches in the late 1940s for simpler life forms like fungi and insects, the first mammal in space was Albert II, a rhesus monkey on June 14, 1949 -- 20 years before humans landed on the moon. Scientists wanted to find out how exposure to all the radiation would affect mammals. Albert II launched in a V2 rocket from White Sands, New Mexico. He reached an altitude of 132 km, and he survived that part, but he died because of a parachute failure during landing. In the Soviet Union, researchers chose dogs over primates, since they thought dogs were more likely to sit still during flight, making them easier to monitor.

And the Soviets were the first to recover mammals alive after space flight. The dogs, Dezik and Tsygan, landed safely in 1951. Then, in 1957, a dog named Laika became the first animal to orbit Earth, though she died a few hours into the flight. These early experiments were crucial in developing the equipment to keep an animal alive during takeoff and while they were in flight. Each launch was a test of new technology. A lot of animals were lost, but scientists learned from these failures, engineering things like better rockets, flight capsules, and landing gear. After some missions failed because of faulty parachutes for example, American engineers redesigned the parachutes, so that in 1951, they were able to successfully recover Yorick, the rhesus monkey, alive. Once they'd worked out those details, they were finally ready to start sending humans out of our atmosphere. Cosmonaut Yuri Gagarin became the first person in space on April 12, 1961, and less than a month later, Alan Shepard because the first American astronaut in space. So, we figure out it was possible for life to survive in space and sent some more humans up there. Animals were still incredibly important for space research, especially when it came to studying the effects of microgravity and radiation exposure. In 2003 and 2004, for example, scientists sent some simple invertebrates to the international space station. A group of nematode worms, C. elegans. They wanted to examine the impact of space living on DNA, whether living and reproducing in space would lead to any observable changes at the genetic or cellular level. C. elegans was a good choice for this research because the worms have a relatively small genome and are sed in research all the time, so their genes have been completely mapped. Plus, with their very short life spans, they're great for studying effects over generations. Overall, the researchers didn't find too many changes in gene expression, but they did find that worms within the same group showed the same small changes. That might mean that different populations might have different sensitivities to space flight, which could explain why some astronauts have a harder time adjusting to orbit than others. These kinds of experiments are still going on today. The ISS even has a special rodent research facility, a habitat designed specifically for studying mice in space. Thank you to all of these non-human astronauts. Thanks to these creatures for starting to better understand how living and moving in space impacts us. With so many different goals comes a huge variety of animals that are best suited for each mission.

Creatures all across the animal kingdom, from worms to sheep, have taken flight in the past. And today, the ISS is home to mice. So here's Reid to explain what they taught us so far about reproduction in space. 

[Reid]: Will we ever live in space long-term? Prominent scientists have argued that the future of our species could lie off-world. But there's one thing we'd need to make that work. Babies. 

It's not just about parenting. Surely our intrepid astronauts would be up for that challenge. It's that some of them would eventually have to get pregnant in the first place. As wild as it sounds, researchers are already trying to figure out if people can make space babies. But so far the results don't look great. 

One major hurdle is the lack of gravity. That includes near weightlessness or microgravity, as well as places with less gravity than our home planet. Like Mars, where gravity is less than half of what we're used to. Most experiments that have tried to shed light on this have been done in real or simulated microgravity, so that's what we'll focus on here. 

But so far, scientists think that even martian gravity would pose problems for conception and gestation. Overall, this story starts out okay. Menstruation in space seems to work normally, at least for short trips. Astronauts often choose to skip their periods for larger missions. 

So although we don't know for sure, that suggests that ovulation would also happen normally. Meanwhile, sperm seem to fair, well, kind of okay in microgravity. Like in 1979, researchers flew live rats on a research satellite for 18 days. And when they got home, they successfully mated with ovulating rats. Except not all of their offspring were totally healthy. 

The growth and development of babies fertilized by mature sperm that were exposed to zero G effects lagged behind control litters. The nice thing is, we might be able to get around this by using space sperm banks instead.

In research presented in 2019, scientists in Barcelona reported some preliminary evidence that frozen human sperm can survive short bursts of microgravity with no ill effects.

Though, their evidence came from specialized aircraft, not from space. Still, it's a start. Now, having healthy cells is one thing, but to get a fetus an egg needs to be fertilized. And there is evidence that sperm can fertilize eggs in microgravity.

One 2009 study used a spinning machine to simulate microgravity and succesfully carried out in vitro fertilization using mouse sperm and eggs. But, even then, fertilization is still a step or three away from pregnancy.

Pregnancy isn't official until an embryo can implant into it's host uterine wall. For that, you need the formation of the blastocyst: a hollow, fluid-filled ball of cells that forms within a few days of fertilization. The layer of outer cells is called the trophoblast which helps the embryo to burrow into the uterine and form the placenta. There's also a clump of inner cells called the embryoblast which gives rise to the fetus itself.  And it seems like embryos might be able to do all that in Space!

Although it hasn't been reported in a peer-reviewed journal, an experiment containing mouse embryos that flew on China's first microgravity satellit saw some of them form Blastocysts which is promising but we'll need more studies to confirm. But even if blastocysts can form in space it's unclear whether they could implant and keep growing. In that same 1979 mission we mentioned, male and female rats were also sent into orbit and allowed to ah, mingle. Some of them did get pregnant but none of them gave birth. The researchers believed that the implanted embryos died and were absorbed back into the rats' bodies. 

Scientists are trying to figure out what exactly it is about microgravity that messes with blastocysts and their ability to impant and grow but they do have ideas. Like embryonic stem cells are part of the equation. These are the cells and the blastocysts that differentiate or diversify into all of the different kinds of tissues in the fetus.  Microgravity appears to make them more resistant to differentiating into those more mature cells. 

And into those more mature cells. It's possible that microgravity interferes with DNA methylation, a process known to affect cell differentiation. Or there could be other factors like how microgravity messes with the behavior of fluids and how cells float in fluids. 

So at this point it's up in the air whether space pregnancy is feasible outside of inventing prolonged artificial gravity. That said, even if we did figure that part out, there's evidence that a fetus couldn't develop in a healthy way in space. After all, gravity isn't only important for the early stages of pregnancy. 

Scientists are pretty sure that it's also important in the third trimester when it helps the fetus develop its muscles, including in the heart. Gravity may even play key roles in the development of synapses in the brain and sensory tissue in the inner ear.

And based on evidence from pregnant mice, it seems like microgravity during orbital space flight affects the development of vestibular functions. Basically the sense of balance and motion. So not great news. And even if we can compensate for microgravity, developing radiation shielding technology strong enough to protect a fetus is a whole other matter.

Outside of Earth's magnetic field, the effects of solar radiation are a lot stronger. And we've learned that the developing brain is extremely sensitive to radiation exposure which can cause DNA damage, brain defects, and increased incidence of cancer. 

So while there's a lot we still don't know about how all this works, and we need many more studies in mammals, one things for sure. We may get there someday, but there's a lot of small steps to come before humanity can make the giant leap to pregnancy in space. 

Savannah: So rodents are teaching us about how we could start life in space, but to learn how space affects an animal later in life, we've turned to fruit flies. I know some of you might be thinking that getting away from those pesky insects is the ultimate perk of leaving Earth, but here's Hank to discuss how space fly has turned them into our little helpers.

Hank: 200 years from now, it's entirely possible that we will have people living off-earth full-time, either on a planet like Mars or in some kind of space station. By then, we'll probably be pros at living in low-gravity environments. We'll have figured out how to solve the problems we have today like how space flight can take a toll on the heart and immune system.

And when we get to that next big chapter of humanity, we'll have a tiny test subject to thank, fruit flies. While they may not seem like useful stand-ins for humans, fruit flies have more in common with us than you might think. Many fruit fly genes mirror the functions of human ones, making them useful in understanding what those genes do. 

They also have some characteristics that make them especially great for studies performed in space. For one, they don't take up a lot of room, which is super important in an environment where space is limited. Thousands of flies can be housed in a container the size of a deck of cards. Also their lifespan is only about two weeks, so scientists can study several generations of them in a month. 

So fruit flies have been sent to space over and over and over again to test different effects of space flight, especially how microgravity affects living bodies. And while we still have plenty of questions, they are already teaching us a lot.

For instance in space, the heart acts a little differently. Like among other things, its muscles get weaker since they're not fighting gravity. We know this is true of other muscles as well. But considering how important the heart is, figuring out exactly how it changes in microgravity will be huge for our long-term future in space. 

And these are, of course, things we're studying in humans, but we can only send so many people to the space station at a time, which means we can only learn so much about exactly what's happening to the heart and how to combat it.

So one study, published in November 2020, used more than 200 fruit flies as a model for how space flight affects cardiac disease and function. The scientists found that flies living in microgravity had smaller hearts that weren't as effective at pumping blood which is similar to what can happen to astronauts. But the researchers also found the flies had problems creating the proteins needed to keep the heart working properly. 

So now that's something else for cardiac researchers to keep an eye on. And eventually, studying these proteins could accelerate the development of new treatments especially for longer missions. But as important as our hearts are, one area of fly research that's been especially fruitful is studying the immune system.

Astronauts experience a suppression of their immune system during and right after space flight that makes them more susceptible to infection. And flies offer a very specific advantage for helping us understand how and why. So the human immune system has two branches: innate and adaptive. The innate immune system is something you are born with. It's essentially a system of barriers that protect against foreign particles like viruses, bacteria and parasites. These include physical barriers like your skin and general immune responses like inflammation. Meanwhile, the adaptive immune system is the part that learns to respond to threats as it's exposed to them using specialized cells and antibodies. 

Untangling what each branch does and how it changes in space is somehow even harder than it sounds and that's where fruit flies come in. They do not have adaptive immune systems. That's limited to us vertebrates. So they can allow us to really dial into just how the innate immune system works without the whole other part getting in the way and confusing things. The key with the innate immune system is that for it to work, your body has to recognize pathogens as foreign objects. Then it can work on fighting them.

To do that, the innate immune system uses molecules called receptors to bind and recognize other molecules on the surface of infectious agents like bacteria and viruses. And when it comes to space flight, studies have found that the immune system can become impaired when communication to these receptors is disrupted. 

Like a 2014 study showed that fruit flies born and raised aboard the space shuttle discovery were a lot more susceptible to certain infections compared to flies on earth. But in that study only one of the two receptor systems the researchers looked at was impaired. The one that responds to fungal infections. The other, which responds to certain types of bacterial infection was unaffected.

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