Stefan: Summer, fall, winter, spring. Every new season brings new diseases. There are all sorts of seasonal illnesses and other ailments, from those you may be all to familiar with, to those you didn't even know are seasonal. But let's start with the painfully obvious: seasonal allergy sufferers don't need to look outside to know when spring arrives.

And spoiler alert- climate change might be making things even worse. Here's how:

Michael: Every spring, around 20% of the population enters the season of sniffles. Just how bad those few months are depends on a lot of things, so usually, some years are worse than others. But lately, there just don't seem to be any better years. And it turns out we can thank climate change for that, as the heat, higher co2 and changing weather patterns all work together to make allergy seasons extra awful.

Seasonal allergies or hay fevers happen when your immune system glitches out and considers benign pollen grains a dangerous intruder. The defense that it mounts leads to common symptoms like a runny nose or itchy, red, watery eyes. For some it's much worse- seasonal allergies can trigger asthma attacks, or exacerbate other respiratory conditions to the point of needing hospitalisation.

So bad allergy seasons are really bad, and unfortunately there are several ways that human-caused climate change is making them worse- for starters there's the timing. You see, when the weather gets warm, the flowers of wind pollinated plants start making pollen, a swarm of microscopic grains that carry the plants genetic material. And I do mean swarm- each grain has a very slim chance of landing where it needs to, so wind pollinated plants always make lots and lots of pollen to beat those odds.

That's why your nose is constantly blasted with the stuff throughout allergy season, and while there are lots of theories to explain what exactly triggers a plant to start producing pollen, ambient temperature plays a key role. Pollen seasons start out when the air and the ground get warmer, and as average temperatures around the globe continue to rise,

both pollen concentrations in the air and the duration of pollen season are increasing. In some places, warmer weather means spring is, well, sprung earlier. For example, the 2018 pollen season in the US started about 20 days earlier and lasted about 8 days longer than the pollen season in 1990, and there was an average of 21% more pollen. But even where that doesn't happen, we're seeing worse allergy seasons.

In some countries, the pollen season now starts later, but scientists are still seeing an increase in allergy symptoms. The reason for the late start is that plants start flowering when they sense a temperature change from cold to warm. That used to mean spring is here, time for love.

But as winters get warmer, spring temperature rises aren't as dramatic, so many species take more time to recognize the season change. This ultimately means species that normally bloom at different times all start spitting out pollen at once, which results in more allergens in the air. That's why we're seeing an 18% higher probability of developing hay fever symptoms in places with later spring blooms, as compared to a 14% higher probability in places where spring now starts earlier, though it's an increase either way.

And it's not just rising temperatures throwing pollen seasons off kilter. It turns out that carbon dioxide itself, the main driver of climate change, also lends a hand. More CO2 boosts photosynthesis, the process plants use to get the energy needed to build more of themselves.

Regardless of temperature changes, most species of plant mature faster mature faster and grow bigger and sturdier when there's more carbon dioxide in the air, and experiments have found that, even though plants in high CO2 don't grow more flowers, the flowers they do grow end up producing more pollen. If atmospheric levels of carbon dioxide keep rising as projected, research suggests that allergenic species may produce up to 200% more pollen by the end of this century.  And just in case that wasn't bad enough, CO2 can also make the pollen itself pack more of an allergenic punch. For example, at higher concentrations of carbon dioxide,

the notorious ragweeds pack more Amb a 1, one of their main allergens, into their pollen grains. And, overall, researchers estimate that the concentration of Amb a 1 in pollen has risen by about 20% since pre-industrial days and will rise another 60% by 2050. And we're still not done, because climate change is also favoring some allergy-inducing plants. Overall, climate change is leading to hotter, drier conditions, and it just so happens that some allergy-inducing species, like hickory, oak, and slash pine, do really well in hot, dry weather, so climate change will likely help them spread.

More of those trees means more pollen and more hay fever. You might think you're safe because you live far away from such forests, but you're probably not, because climate change may make it so that their pollen can still get to you. Some research suggests that changing wind patterns will expose people to pollen species from 100s of kilometers away, leading to new or unexpected allergies, or the winds may deliver pollen to areas before the local pollen season starts.  So basically everything about climate change, from rising temperatures to weather patterns, seems to be working against your nose.

But, though all of this might sound pretty grim for people who experience seasonal allergies, all hope is not lost. It's more a reminder that the time to act is now, while we can still prevent the sneeze-y future climate has in store for us.
Stefan: And allergies aren't the only things that suck; so do mosquitoes. And it turns out that we aren't only allergic to pollen in the air; we're also allergic to bug bites. Here's more on why bug bites are so dang itchy.

Hank: Here's a vexing question asked at picnics and beach parties everywhere - why do bug bites itch? And the answer is: they don't. Bug bites don't itch at all. Sometimes you don't even feel them, and that's pretty amazing, because what goes on under your skin when a bug bites you is horrifying.

Alright, some insects, like certain kinds of ants, are venomous, so their bites can itch because their venom contains formic acid,

which can irritate and blister the skin. But let's talk about nematocera, the suborder of insects that includes black flies and mosquitoes. These bugs have a long, bendable proboscis that they stick into you to drink your blood. The proboscis is made up of six different mouth parts.

First, you've got the mandibles, which are hooked, and the two maxillae, which are serrated like steak knives. These sharp bits go as deep as they can to make an opening for the other two mouth parts to pass through, the labrum and the hypopharynx. Those are both long, hollow, flexible tubes, and they wriggle around inside of you like a worm while the bug probes around for blood vessels.

Once it finds one, blood gets sucked up through the labrum, and saliva is injected down through the hypopharynx. That saliva is an anti-coagulant. It stops your blood from clotting inside the bug's proboscis so that it can keep drinking.

It's also the main vector for diseases that are transmitted by mosquitoes, like malaria and West Nile virus. And it has one other awesome property - you are probably allergic to it, and when you're allergic to something, your body produces histamine, the protein that triggers inflammation and widens your capillaries to allow white blood cells to pass through them so that they can fight foreign invaders. So it's the histamine that makes you swell up and itch when you get a big bite, just like it makes your eyes and nose itch during pollen season.

We're not even sure why histamine needs to make you itchy in order to do its job. It might just be your body's way of telling you that something's wrong with your skin, but I'm pretty sure we all wish it would stop.
Stefan: Spring and summer are full of allergies on top of allergies, but you probably already knew that allergies are seasonal. Well, plot twist, genes can also respond to the changing seasons. Here's how.

Hank: It'll soon be summer here in the Northen Hemisphere and winter for those of you on the other half of the planet. Of course, plenty of things change with the seasons - the weather, the number of daylight hours, whether or not you have school. And according to new research, there are other things that change as well, like your genes.

For a long time, doctors, patients, and researchers have noticed that some diseases, like heart disease, type 1 diabetes, and rheumatoid arthritis, seem to get worse during the winter, but they weren't sure why. Now, it looks like there's a very good reason. Genes associated with your immune system seem to change expression, that is basically to turn on and off, based on the season. Researchers from the UK and Germany studied the genomes of more than 16,000 people from all over the world, using blood and fat samples that had been collected at different times of the year.

Since your genes code for particular proteins, if a sample had more of a certain kind of protein at a specific time of year, that meant the gene associated with it was more active, and the patterns that showed up in the subjects showed some clear similarities. Out of nearly 23,000 genes, over 5,000 were more active certain times of the year, and the patterns were actually reversed in people who lived in different hemispheres, so genes that were more active in a German during December were also more like to be active in an Australian in June. One immune system gene, ARNTL, is known to suppress inflammation in mice, and it turned out to be more active in people during the summer.

This could explain why some autoimmune diseases, like rheumatoid arthritis, tend to flare up in winter, because that's when the genes that help reduce inflammation aren't expressed as strongly. Similarly, genes that code for antibodies that fight diseases like yellow fever, influenza, and meningitis were found to be more active during the winter. Now, that makes some sense, because winter is flu season, but it also means that winter may be the most effective time to vaccinate against these diseases so vaccines can evoke the best possible response from your immune system.

As for the gene that showed the strongest seasonal preference, geneticists known which protein it codes for, but they have no idea what it does. So, yeah, we have a lot more to learn, but the results suggest that our bodies may be more in tune with our yearly trek around the Sun than we thought.
Stefan: Genes affect so much in our lives, from the color of your hair to your likelihood of developing certain cancers, and cancer is another surprisingly seasonal illness. Now, I don't mean that it miraculously goes away in the fall, but certain cancers have a higher survival rate

Rose: We're all pretty familiar with cold and flu season, but a few decades ago, public health experts began to notice that some noninfectious diseases, like breast cancer, followed a seasonal pattern, too, which might seem strange, because we don't talk about a cancer season the way we talk about flu season. But these annual spikes can teach us a lot about how our bodies interact with the environment. Scientists explain the seasonality of infectious diseases like the flu by looking at a bunch of different factors, things like how the host's behaviors spread the disease or how the biology of the virus changes over the course of the year. The influenza virus is transmitted most effectively in cool, dry weather, so even though you can get the fly whenever, fall and winter are its favorite time of year.

But diseases that aren't caused by germs can see regular seasonal spikes for totally different reasons, like the influence of the Sun. We've known for a long time that excessive exposure to sunlight increases someone's chances of developing skin cancer. That's because ultraviolet radiation from the Sun damages DNA and interferes with its ability to repair itself, a fairly routine process that DNA does constantly, and more people are diagnosed with skin cancer in the summer months than in the winter.

In the long term, we also see more skin cancer diagnoses along with the solar cycle, an 11-year fluctuation of solar activity. Simply enough, when the Sun emits more UV, we see more skin cancer. The solar cycle doesn't affect your individual risk as much as, say, wearing sunscreen, but there's enough of an impact that we can see it in the overall population.  While skin cancer has a pretty well-understood mechanism, the spike in coronary artery disease that doctors see every winter is not as straightforward.

Our circulatory systems respond to drops in temperature by constricting our blood vessels. When that happens, the heart has to pump blood against more resistance, which increases blood pressure, and high blood pressure is an important risk factor in cardiovascular disease.

And studies in rodents suggest that reduced temperature also impairs the body's ability to make nitric oxide, a chemical that expands blood vessels and reduces blood pressure. Certain hormones also fluctuate with temperature. For instance, thyroid hormone helps regulate how forcefully our hearts contract and expands blood vessels, and exposure to cold conditions decreases thyroid hormone levels. Cardiovascular disease is caused by the interaction of so many different factors that it's hard to point to just one thing that makes the biggest difference, but these factors might give insight to a larger trend.

Breast cancer is another disease that sees a seasonal spike in diagnoses in the spring and fall, and a patient's chances of survival are usually better if it's diagnosed in the summer than in the winter. And that puzzles scientists, because breast cancer can be developing for years before it's detectable, so it shouldn't matter when you find it. Breast cancer can grow quickly, though, and something has to explain those clear seasonal peaks and valleys.

So, in the last few years, researchers have been looking for anything that might cause faster growth rates and push more breast cancers to the point where they're more easily detectable on a mammogram. We know that some types of breast cancers can grow faster thanks to estrogen receptors on their cells. Those cells tend to grow faster in the presence of estrogen.

Since estrogen sees annual peaks and valleys, this seasonality of the hormone might explain the seasonality of the disease, but the same seasonal spikes in breast cancer diagnoses are seen in people with ovaries, which make estrogen, both pre- and post-menopause. Since the body makes much less estrogen during menopause, we'd expect to see some kind of difference if it could be explained by that hormone. So scientists have looked into other substances that fluctuate throughout the year, including vitamin D and melatonin, and here's where it gets a bit complicated.

Our bodies create more vitamin D during the summer, thanks to more sun exposure, and mammals create melatonin at different times of the day in response to darkness, so some researchers think that the rise in vitamin D

protects us during the summer, while melatonin protects us during the winter, thus explaining the spring and fall peaks in breast cancer. And, in the last few decades, different studies have shown that treating breast cancer cells with a vitamin D derivative might prevent them from growing and encourage them to die outright. Breast tissue has an enzyme that converts a vitamin D precursor molecule into that supposedly beneficial derivative, and those cells can also have the ability to pick up vitamin D as well. A 2019 meta-analysis of 70 studies showed that low vitamin D levels in the blood were associated with increased risk of breast cancer, and it's the same story with melatonin.

Early studies showed that melatonin slowed the growth of breast cancer cells in the lab, and studies since then have shown that it can modify estrogen receptors on certain types of breast cancers. But that's not the end of the story. There's some support for both of these mechanisms, but, overall, the evidence is mixed.

A meta-analysis from 2017 found no association between urinary melatonin levels and breast cancer risk, but previous meta-analyses found that less melatonin did increase breast cancer risk. Researchers have also conducted randomized controlled trials, the gold standard for investigating a causal relationship, and found vitamin D supplementation had no effect on the incidence of breast cancer. That means we're not really sure yet why breast cancer has that weird double seasonal peak.

It'll take a lot more research to know for sure. In general, it's a combination of factors that predispose us to certain diseases, so teasing out causation from correlation can be tricky. Regardless, there are a lot more patterns, and a lot more reasons for patterns, in illness than we might have realized.
Stefan: Unfortunately, fall might be a worse time for cancer, but it's also the start of another, more familiar season - flu season. Now, do the changing colors of the leaves redeem fall enough to get through all of this sickness? Well, probably not, but we're stuck with flu season either way, so how do we fight it?

Michael: Do you feel that chill in the air?

In a lot of places around the world, including North America and Europe, it's that lovely time of year known as flu season, and, each year, we try to fight flu season with the influenza vaccine. Every season is kind of a whole new battle for researchers, because flu viruses evolve very quickly, and this year is no different.  The fact that there is a flu season means doctors and healthcare organizations can prepare for it, but why is there a flu season at all? Why isn't there just flu flying around everywhere all year? Well, there are actually two flu seasons every year, because the Northern Hemisphere and the Southern Hemisphere experience winters at opposite times of year.

So here in the United States, for example, flu season lasts from about November through March, and countries in the Southern Hemisphere typically face the flu between May and September. The flu virus does circulate year-round, but the number of cases rapidly increases during these peak months, giving influenza its own holiday season to celebrate. Research suggests that winter months are ideal for influenza transmission because they bring a combination of cool air and low humidity.

Influenza virus is transmitted through droplets from a sneeze or a cough that are carried in the air. When temperate and humidity are low, these droplets can fly easily through the air without much resistance, but, in warmer and more humid climates, the extra moisture in the air makes the droplets bigger and heavier, and therefore more likely to fall out of suspension in the air, so the virus can't travel very far. And, of course, cooler temperatures mean that people tend to stay indoors, increasing the number of potential bodies in an enclosed space for the virus to infect.

Makes sense, right? But even if the influenza keeps going from one hemisphere to the next, why do we need a different vaccine every year? Each flu season is unique because the influenza virus mutates from year to year.

There are three major types of influenza, labeled A, B, and C, and influenza A viruses are further categorized into subtypes depending on the two proteins that coat their outer shells. There are the HA, or hemagglutinin proteins, and the NA, or neuraminidase proteins. These proteins act like beacons to a host cell, tricking the cell into letting the virus attach and infect it.

There are different subtypes of these proteins, H1 through H18 for the hemagglutinins and N1 through N11 for neuraminidase, so the different combinations are why we talk about flu strains in terms of,

say, H1N1 or H3N2. But these HA and NA proteins mutate very easily through a process called antigenic drift. These small changes don't alter the virus very much, but, after some time, the changes accumulate and can result in a new strain of virus that acts in a completely different way than the original did. And sometimes, in rarer cases, genetic mutations in the virus can cause big, dangerous changes.

This is called antigenic shift, and it can result in a brand new combination of genes that make the virus much more infectious. You might remember the antigenic shift that happened back in 2009. That's what created swine flu.

So, with different viruses mutating all the time, how do we know which strains are the ones we should get vaccinated against this winter? Four strains are selected based on data collected throughout the year by health organizations monitoring flu activity in various countries around the globe. They report it to a network run by the World Health Organization, which then compiles the data to predict which strains will likely be circulating during peak seasons, and they come out with recommendations for that year's vaccines.

Since the Northern Hemisphere and Southern Hemisphere tag team winters, usually the data collected during one flu season will help inform the other hemisphere about which strains are doing the most damage and if the vaccines were effective or not. Flu vaccines are actually developed months before peak season starts to allow time for them to be made and tested, but that means that sometimes the viruses that are circulating change while the vaccines are being produced, so the vaccines might end up not being as effective. So what strains are we up against this year?

There's A/California/7/2009 (H1N1) PDM09-like virus, whose really long name comes from things like its type, where and when it was first isolated, and the subtype of its HA and NA proteins. It's an influenza A virus isolated from California that's closely related to the strain that caused the 2009 H1N1 pandemic. Then there's the A/Hong Kong/4801/2014 (H3N2)-like virus and a strain called B/Brisbane/60/2008-like virus, which comes from a line of B viruses from Victoria, Australia.

It gets a slightly shorter name, because influenza B viruses aren't categorized by subtype. In the quadrivalent vaccines, like the nasal spray version, a fourth strain is included and is called B/Phuket/3073/2013-like virus, descended from the Yamagata, Japan

lineage of B viruses. So, just like spring, summer, fall, and winter, flu season is an inevitable season that comes back year after year, but scientists do their best to fight it by working year-round to keep us up-to-date and protected from the ever-changing flu. So if it's almost winter where you live, go get your flu shot, and, if you haven't yet, brace yourself - flu season is coming.
Stefan: And finally, no winter would be complete without this last illness. Always spoken of hand-in-hand with flu season is cold season. So, how did the cold get its name, and why are we more susceptible to it in the winter? Here's why it's so common to come down with colds when it's cold.

Michael: At some point during your childhood, you were probably told not to go out in cold weather with wet hair or without bundling up because you'll catch a cold. But we know the common cold is caused by viruses, not chilly air, so why does this old wives' tale hang around? It's probably because colds are more common in colder weather, but, as far as scientists can tell, that's not because you feel cold. There are lots of better explanations for why colder weather increases your odds of getting sick.

The connection between temperature and illness isn't simple. Even though colds and other respiratory illnesses are more common in colder months, not all of them spike in the dead of winter when it's coldest, and the most direct studies we've done haven't found a relationship between feeling cold and catching a cold. For example, in a randomized controlled trial published in 1958, researchers divided nearly 400 people into rooms that were either 27 degrees, 16 degrees, or -12 degrees Celsius.

Then, they put virus-infected mucus up some of their nostrils, but the temperature didn't make a difference. In every room, just over 1/3 of the volunteers that received the infected mucus got sick. One Study from 2005 did find that people who had their feet soaked in freezing cold water reported more cold symptoms in the days afterward compared to a control group, but it's hard to tell how much of that was influenced by subject's thinking they'd be more likely to get a cold.

If feeling cold really does make you more likely to get sick, there are a couple of ideas that might explain it. One hypothesis argues that even though the cold doesn't weaken your immune system overall, it might lower the defenses in your respiratory system, specifically.  And in a paper

published in 2016 in the journal Medical Hypotheses, a microbiologist suggested that viruses lie dormant for extended periods of time in our bodies, then get activated when the temperature drops.  There are lots of problems with those ideas, and the vast majority of research shows that simply being cold doesn't make you more vulnerable to catching colds. Instead, there are other aspects of cold weather that might increase your chances of getting sick. Like the fact that the air is super dry. Colder weather is associated with lower humidity, because at lower temperatures, the air can't hold as much water.

When humidity is high, the droplets of virus-infected grossness that we breathe out or sneeze out or cough out of our bodies stay large, and drop to the floor relatively quickly. But in dry area, they break up into smaller particles and can float around for hours. Plus, the lack of moisture can dry out the mucus lining in your nose, which might make it easier for viruses to get past that line of defense.

Another potential problem is that some people don't get enough sunlight in the winter, making them run low on vitamin D. Since vitamin D helps power your immune system, lower levels mean lower defenses against viruses. And then there's the fact that human behavior changes during colder months.

We're more likely to stay indoors, which means we're more frequently touching stuff infected people touched, and breathing in the remnants of their sneezes. [Deep Inhale] Mmm. So researches are still trying to pin down all the different ways cold weather may or may not affect how likely you are to catch a cold. But the best way to avoid catching one isn't necessarily by throwing on another layer or drying out your hair before running out the door.

It's washing your hands with soap, not touching your face with unwashed hands, and staying away from people you know are affected. [New Speaker]: Each season brings its own challenges and rewards. I'm still glad to have the flowers blossom even if my body responds kind of poorly to the pollen. And at least during cold and flu season, there aren't many mosquitoes giving me allergic reactions.

Thank you for watching this episode of SciShow, and if you love watching SciShow in every season, you might enjoy this video about why humans don't have a mating season. [Outro Music]