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Scientists have been turning to the animal world for inspiration for a long time, including for medicines. And many different types of animals have been responsible for this inspiration, including sharks, spiders, and... roadkill.

Hosted by: Michael Aranda

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Sources:
Intro
https://lemelson.mit.edu/resources/otto-lilienthal
https://www.hookandloop.com/invention-velcro-brand/
https://biomimicry.org/biomimicry-examples/#construction

Frogs
https://www.acs.org/content/acs/en/pressroom/newsreleases/2010/august/frog-skin-may-provide-kiss-of-death-for-antibiotic-resistant-germs.html
https://www.nature.com/scitable/definition/peptide-317/
https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity
https://www.sciencedirect.com/science/article/pii/S0924857906001026?casa_token=kd7aaejRbHcAAAAA:0p6llm5xh0HZeGjrfz7JugDaTBLhQEeTHITOjGnhtITL8pFnvcciFafZoUYCfEBkJJOrPGU9AA
https://www.researchgate.net/profile/Andrea-Rinaldi-7/publication/321616913_Antimicrobial_Peptides_Methods_and_Protocols/links/5a3bddacaca272dd65e4b616/Antimicrobial-Peptides-Methods-and-Protocols.pdf#page=15
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1747-0285.2008.00671.x?casa_token=AVXGzLAv1BMAAAAA:e948bW6RQBrCzh1txPciwa4XacFnbKwHeGPY8ARsnfTJDYIQJoGEIS-2JLBRKh5rY8gRN3vS4aM5vdU
https://link.springer.com/content/pdf/10.1007/s00726-012-1395-7.pdf
ncbi.nlm.nih.gov/pmc/articles/PMC7087712/

Sharks
https://academic.oup.com/abt/article/3/1/1/5706878#218994223
https://www.khanacademy.org/science/in-in-class-12-biology-india/xc09ed98f7a9e671b:in-in-human-health-and-disease/xc09ed98f7a9e671b:in-in-types-of-immunity-and-the-immune-system/a/adaptive-immunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112388/
https://www.bioatla.com/appendix/antibody-structure/#:~:text=The%20variable%20domain%20is%20also,for%20binding%20to%20the%20antigen.
https://www.ossianix.co.uk/vnar-libraries
https://www.sciencemag.org/news/2018/05/mini-antibodies-discovered-sharks-and-camels-could-lead-drugs-cancer-and-other-diseases
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213394

Venom
https://www.bbc.com/future/article/20200507-medicines-and-drugs-from-animals-venom
https://www.britannica.com/science/ion-channel#ref287525
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389327/

Sponges
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930278/
https://issues.org/p_bruckner-coral-reefs-importance/
http://chemocare.com/chemotherapy/drug-info/ara-c.aspx
https://www.britannica.com/science/antimetabolite
https://www.tocris.com/cell-biology/cell-metabolism

Roadkill
https://cen.acs.org/articles/95/i16/Roadkill-drug-discovery.html?ref=search_results
https://microbiologysociety.org/blog/what-is-a-microbiome.html
https://depts.washington.edu/ceeh/downloads/FF_Microbiome.pdf
https://pubs.acs.org/doi/abs/10.1021/acs.jnatprod.6b00772
https://www.cdc.gov/fungal/diseases/candidiasis/index.html

Images:
https://commons.wikimedia.org/wiki/File:Rana_boylii02.jpg
[♪ INTRO].

Scientists have been turning to the animal world for inspiration for a long time. Some of our first attempts at powered flight were based on the flapping of birds’ wings.

Velcro was invented after observing how burrs stick to fur. And engineers are mimicking termite mounds when designing ventilation systems for buildings. But maybe the first thing we think of, when it comes to deriving useful stuff from the natural world, is medicine.

And animals have clued us into all sorts of remedies over the years. Take frogs, for instance. They’ve been around for about 300 million years, which has given them plenty of time to learn how to defend themselves against disease-causing microbes.

That’s only become more true as humans have reshaped their habitat, so it’s no surprise that these amphibians have developed a lot of defenses. Scientists have identified more than 100 antibiotic substances produced by frog species around the world, specifically, in their skin. These substances are peptides, which are short chains of organic compounds called amino acids.

Those are the same components that make up proteins, a peptide is similar, but generally shorter and less complex. Many organisms, including frogs and humans, make peptides that target microbes. These play an important role in the body’s innate immunity, which is the part of your immune system that you’re born with.

It’s your first line of defense against pathogens. Antimicrobial peptides work differently from traditional antibiotics. Certain antibiotics kill bacterial cells by binding to specific proteins on the cell membrane and weakening it until it bursts.

Antimicrobial peptides instead exploit the main component of cell membranes, phospholipids. Those are molecules that form a double layer to enclose the cell. And antimicrobial peptides disrupt those layers and punch the membrane open.

This makes it difficult for microbes to develop resistance to the peptides, since they’d need to redesign their membrane to stop them. Which is just… super unlikely. Scientists have known for a long time that frog skins contain peptides capable of killing not just bacteria, but also viruses and fungi.

So it seems like they’d make a useful antibiotic. Except, because these peptides are toxic to humans, our bodies destroy them. Or at least they did... until one group of researchers found a way to substitute some of the amino acids in the chain and make the peptides less toxic and less easily destructible.

This opened up a world of antimicrobial peptides for scientists to apply to various diseases. One example is a peptide called Brevinin-1BYa, found in the skin secretions of the foothill yellow-legged frog. In a 2006 study, researchers found that a tweaked artificial version of this peptide could inhibit the growth of methicillin-resistant Staphylococcus aureus bacteria, better known as MRSA.

That’s a superbug that causes outbreaks in hospitals, schools, and nursing homes. The synthetic frog peptide still needs to be studied further before it can be applied clinically. But researchers have now identified more than 350 types of peptides belonging to this Brevinin family, with applications ranging from cancer treatment, to insulin production, to wound healing.

Another inspirational ancient animal with a robust immune system is the shark. Sharks have existed for about 500 million years, and have the oldest form of adaptive immunity we know of. Unlike the innate immune system, the adaptive, or acquired, immune system is one that you... acquire.

When antigens like viruses or toxins enter the body, it develops specialized proteins called antibodies to fight them off. The antibodies recognize and bind to specific parts of the invader, known as antigens. In 1995, scientists discovered that sharks produce an antibody that has some potential advantages compared to our human ones.

You could say when it comes to fighting pathogens, this shark antibody has more teeth. Researchers thought it could be really useful as a diagnostic or treatment for a variety of diseases. Sharks’ secret weapon lies in the part of the antibody that binds to antigens.

It’s called the variable domain, or VNAR. Compared to your basic Y-shaped human antibody,. VNAR is smaller and has a different shape that allows it to penetrate deeper into tissue.

That gives it better access to hidden or hard-to-reach binding points on antigens. Scientists can also change how fast VNAR is broken down or absorbed by your body. On top of that, it’s also more stable at high temperatures.

Armed with these advantages, many research groups are developing VNAR as potential therapies for conditions including malaria, multiple sclerosis, solid tumors, polyarthritis, and even for treating viral diseases. They’re even creating a VNAR antibody library using nurse sharks. Another animal-generated treatment comes from a more unlikely source: venom.

Venoms are some of the most complex chemical compounds on Earth. They’re produced by 15% of all animal species. These toxins have incredible potency, stability, and speed.

But we know what you’re thinking: How can something toxic be used in medicine? First, not everything that’s toxic to other animals is toxic to us. Out of over 100,000 spider species, only a few are dangerous to humans.

Second, venoms can precisely target specific molecular components. This amazing precision is what makes dangerous side effects very unlikely. And it also makes venom a targeted tool for potential therapies.

Like frog skin, venom contains peptides. But in this case, the peptides target ion channels. The job of a cell membrane is to keep the stuff inside the cell on the inside, and the stuff outside the cell on the outside.

But ion channels create a pathway for electrically charged atoms or molecules, called ions, to pass through. When this happens, the difference in charge on the outside versus the inside changes. That triggers a physiological effect, like a muscle contraction.

So, by interacting with certain ion channels, these peptides can alter certain bodily functions. For example, Hi1a is a peptide found in the venom of. Australian funnel-web spiders, a group that includes a few dozen species.

This potentially deadly venom is a mixture of 3,000 molecules and has been described as “the most complex chemical arsenal in the world.” The Australian-based researchers responsible for that description were looking for a way to reduce the amount of brain damage that occurs after a stroke. And Hi1a proved to be exactly what they needed, because even though the funnel-web spider can kill humans, this particular peptide is harmless to us. And crucially, Hi1a has an interesting way of interacting with a particular ion channel in the brain.

It’s called acid-sensing ion channel 1a. And it’s responsible for the neuronal damage that results after a stroke, due to a build-up of acid. In experiments performed on rodents, when this ion channel was inhibited through genetic manipulation or drugs it decreased neuronal death.

The researchers found that Hi1a can also inhibit this ion channel. A small dose given to rats within 4 hours of a stroke reduced the brain damage that occurred by 90%. And what’s great about Hi1a is that it’s reversible.

So it allows the ion channel to begin working again after the dangers created by the stroke have passed. In addition to Hi1a, venoms provide many other useful peptides that are being investigated as treatments for conditions including epilepsy, cancer, autoimmune diseases, and chronic pain. Another unlikely critter that’s provided us with an arsenal of medicines is the marine sponge.

They may seem simple and unassuming. But in fact, they’re something of a treasure trove. Unlike most animals, sponges can’t move and don’t have physical defenses.

This makes them vulnerable to predators like fish and turtles. But they do have a lot of defensive chemicals to deter these predators. And many of these chemicals are useful to humans.

Each year, hundreds of new chemical compounds are discovered from sponges that have interesting pharmacological possibilities. Some have already made it into clinical trials as treatments for cancer, microbial infections, inflammation, and more. One of the earliest examples is a commonly used chemotherapy drug called Cytarabine, also known as Ara-C.

It was developed from an extract of sponges that live on the Carribean Reef. Specifically, it came from their nucleosides, which are parts of nucleic acids like DNA and RNA. It’s currently used to treat lymphoma and leukemia, while a related medicine is used to treat lung, pancreatic, breast, and bladder cancers.

Many forms of chemotherapy kill cancer cells by preventing them from dividing. And Ara-C is in a specific class of chemotherapies called antimetabolites. They prevent cell division by infiltrating the cells and gumming up the works.

Because Ara-C resembles a specific component of DNA, cells can grab it by mistake when they’re trying to copy their genomes and divide. But because it’s not quite right, it messes up DNA replication, and therefore halts cell division. And it’s all thanks to the humble sponge, which is one of several coral reef dwellers being looked at for potential treatments for everything from viruses to Alzheimer’s disease.

Finally, from coral reefs, we go to a pretty unusual source of medical research subjects: dead animals on the roadside. Yes, we’re talking about roadkill, which has given us a new, hassle-free way to study the microbiome. A microbiome is a community of microorganisms that live together.

All living things have them, including us. But they’re also found in soil, ocean water, and buildings. In humans, they’re an essential part of our development, nutrition, and immunity.

Studying them can help us learn more about infectious diseases and chronic illnesses, and even discover new medicines. And researchers at the University of Oklahoma came up with an out-of-the-box idea for investigating microbiomes. Rather than search for novel microbial samples in live critters in nature, which presents a host of challenges, they find it more convenient to use roadkill.

They search for animals who haven’t been dead too long, so their microbiome closely resembles that of a live animal. Then they swab them and bring the tubes back to the lab. There, they isolate microbial samples and identify potentially interesting compounds.

From bacteria found in the ear of an opossum, they found molecules that can prevent a common fungal infection. The molecules are called serrawettins. And in the team’s experiments, they were able to prevent the growth of the yeast Candida albicans.

Candida naturally lives on and inside humans without causing any problems. They even help with gut health, nutrient absorption, and digestion. However, when this yeast overgrows, it causes candidiasis – the most prevalent form of fungal infection in humans.

But because it’s usually a harmless passenger, instead of eliminating Candida completely, it would be most beneficial to control its growth. The team found that low concentrations of serrawettins could moderate the growth of Candida, rather than wipe it out. So it’s possible that serrawettin-based therapies could be on their way to a pharmacy near you.

And you can thank roadkill, researchers, and the field of animal-inspired medicine for your cure. But in the meantime, I’d like to thank our patrons for making this, and every episode of SciShow possible. We couldn’t do it without you guys.

If you’d like to become a part of our amazing community, you can check out patreon.com/scishow. [♪ OUTRO].