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Go to Brilliant.org/SciShow  to see how you can take your STEM skills to the next level. [♪ INTRO]. Some of the most cutting-edge medications  are also the most complicated.

They’re called biologics, and most  of them are made... by hamsters. Well, hamster cells. These complex molecules are  used for cutting-edge treatments for cancer, autoimmune diseases, and more.

And they’re so heavy-duty that we can’t  just put them together in a test tube. We need living cells to make them for us. So about two-thirds of  biologics are made specifically in Chinese Hamster Ovary cells, or CHO cells.

And while you’re writing that  down for your next trivia night,. I’ll tell you it’s for a good reason! Those little hamsters are biochemical  geniuses.

I mean, not literally — but their cells are so handy, biology  wouldn’t be the same without them. Biologics can be pretty much any  therapeutic treatment made by living things. But we often use the term to refer  to drugs that are made from proteins.

They can be replacements for the proteins  our bodies would normally make, or sticky antibodies designed to seek and latch onto  a specific target, among other things. And while making a protein is  tough for us to do in the lab because they’re so complex, living things  have been doing it for billions of years. So we can design these drugs to do amazing things… but we usually ask living  cells to make them for us.

To understand how one hamster’s ovaries  came to fill this particular role, we need to go all the way back to the year 1919. Many people were dying of pandemic influenza, and it was pneumonia that  often dealt the final blow. But pneumonia-causing bacteria can come  in a few varieties, and to treat it, a doctor needs to know what type  their patient is infected with.

At the time, one way to  identify the bacteria involved using the patient’s sputum  to infect a bunch of mice. In China, a researcher named E. T.  Hsieh wanted to follow that protocol to help his patients, but there  was actually a shortage of mice.

Chinese striped-back hamsters, on  the other hand, were really common. According to one account, Hsieh was  walking down the street in Beijing and noticed some kids selling  captured hamsters as pets. So of course, he decided to give them a try as a substitute for lab mice.

And it worked! Hamsters have a lot going for them as lab animals: they’re small, they’re easy to care  for, and they usually don’t get sick unless a researcher purposely  infects them with something. So, in the 20 years after  Hsieh’s pneumonia research, scientists used Chinese hamsters to study  all sorts of disease-causing organisms, from viruses to bacteria to parasites.

The only catch is that the hamsters were  so aggressive, that they needed to be housed in separate cages or else  they would literally kill each other. So, for decades, scientists  couldn’t breed them in the lab. Instead, labs paid farmers  to catch hamsters for them.

The little guys were a common crop pest, and scientists used them by the thousands. Eventually, the hamsters were transported  to the US, where researchers worked out how to get them to breed without  immediately killing each other, which made them viable as a  lab animal outside of China. Then, in 1951, researchers discovered  something else about these animals: the hamsters only have 22 chromosomes.   Now, that’s a weirdly small number  of chromosomes for a mammal.

Humans have 46; rats have 42, and mice have 40. But, this was still the dawn  of genetics, when figuring out what chromosomes do was an active pursuit. Thanks to experiments in the 1940s,  the scientific community knew that chromosomes carried heritable  traits from parents to offspring.

A small number of chromosomes  made Chinese hamsters a promising model for studying them further. Biologists do that by studying mutations. Like, what happens when the  animal has an extra chromosome?

Or when just a chunk of the  chromosome has been copied, or moved from one chromosome to another? Researchers can isolate and examine  chromosomes under a microscope, where these kinds of changes are often visible. And a small number of chromosomes  makes everything easier to spot.

Now, you can’t look at chromosome  mutations by looking at a whole hamster — or at least, it’s not terribly efficient.  And this is where cells come in. See, this was also a time when  scientists were just learning how to consistently get mammalian cells  to grow outside of the organism. In the late 1950s, scientists  at the University of Colorado got a hold of one of these hamsters and  turned several of its cells into cell lines.

A cell line is a single type of cell  that’s been made to grow and copy itself indefinitely in a dish or a test tube. One of the cell lines that grew  well just happened to come from the hamster’s ovaries —  and those became CHO cells. CHO cells found a place not just in  the study of chromosome structure, but also in toxicology,  immunology, and cell physiology.

They were used in discoveries like  how cells receive external messages, how they keep their shape, and how they  can stick to each other or move around. By the 1970s, researchers realized that  they could not only study how cells work, but change how they work  with new DNA editing tools. Thus began the era of biomedical  engineering for pharmaceuticals.

So, some diseases are caused because the  patient’s body lacks a particular protein. The idea with biologics is that if you can  make that protein and give it to the patient, that could help treat their disease. Type 1 Diabetes is a fantastic  example.

It’s caused by a shortage of the protein insulin. So it can be treated  by administering insulin to the patient. That insulin used to be pig insulin.

Then, scientists realized that they  could take the human gene for insulin, put it in E. coli bacteria, and  the bacteria would read that gene and start making insulin protein for them. And behold: E. coli-grown  insulin hit the market in 1982. Now, insulin is a relatively  simple biologic drug — it’s a protein with just two subunits, or pieces.

But insulin is far from the only  protein we’d like to be able to make. Just one of the simplest. Antibodies, for example, have  fantastic potential as medicine.

Normally, they’re parts of our immune  systems that attach to specific targets. They latch on to disease-related molecules and flag them for destruction  by the patient’s immune system. And we can tailor them to  attach to anything we like — which can be very useful in interfering  with the progression of certain diseases.

But antibodies are more complex than  insulin. They have four subunits. E. coli can’t handle such a large project.  The genetic code that translates to protein is the same from bacteria to humans, but  the way we process proteins is different.

So to make more complex proteins, bioengineers turned to one of the  best-studied animal cell lines: CHO cells. But that’s still more challenging than it  sounds, because it’s harder to convince animal cells like CHO cells to pick up  new DNA, compared to bacterial cells. Bacteria are prokaryotes — they just have  one membrane to hold in their insides, with maybe a cell wall to make things stronger, and then all of their proteins  and DNA float freely inside.   On the other hand, animals are eukaryotes, meaning their DNA is contained in a nucleus,  separated from the rest of the cell.

To introduce a gene into bacteria, you  just have to get the DNA past one membrane. For animal cells, it has to get past two. But in the 1980s, researchers figured  out how to basically extort CHO cells into accepting the genes for biologic drugs.

Here’s what you do: You start with  a CHO cell line that lacks the gene to make an important nutrient. Grow the cells in medium that has that  nutrient, so everything’s fine and dandy. Then, you create a piece of DNA with two genes.

One is for your biologic. The other  is to produce that important nutrient. When you mix that DNA in with the cells,  some of the cells will bring the DNA all the way into their nucleus,  but a lot of them won’t.

So here’s the key part: you take that  important nutrient out of the growth medium. Any cells that didn’t suck up that  DNA will die, leaving behind cells that did pick up the nutrient  gene… and the one for the biologic. This was a major breakthrough for drug  production.

It was a reliable way to get genes for drugs into CHO cells, which turned  them into little self-replicating factories. And the first drug made using  CHO cells, a blood clot thinner, was released in the late 1980s. Now, we’ve implied that CHO cells are used  for this because they were… just there.

And certainly, it doesn’t  have to be hamster ovaries. Around a third of protein-based drugs  are made using other cell lines. But in a lot of ways, CHO  cells have the advantage.

They accumulate mutations relatively  slowly compared to other cell lines, so whatever gene scientists  introduce to make a drug will probably remain intact for a long time. They’re also rodent ovary cells, so human  viruses are unlikely to cause problems as a source of contamination. And they can be grown in big vats of  liquid, which is actually important.

A lot of cell lines like to  grow stuck to a solid surface — it’s closer to their natural state. But CHO cells don’t, and  it’s way more space-efficient to be able to grow your cells in 3D culture  than stuck to a billion Petri dishes. Finally, they do a really good job of  making the actual proteins we need.

Proteins are made of amino  acids, but that’s not all. Cells add a finishing touch:  a sprinkling of sugar. No, really: they attach groups of sugar  molecules in a process called glycosylation.

Every species has a different way  of glycosylating their proteins, and if you try to put a protein with  the wrong sugar pattern into your body, your immune system will recognize  it as not human and destroy it. But good old CHO cells have nearly  identical sugar patterns to human cells. So drugs produced in CHO cells  are ready to go, sugars and all.

CHO cells are one of the most important  biological systems in medicine. They’ve been used to make drugs  that treat arthritis, psoriasis, and even play a part in producing  chemotherapy to treat cancer. And it took a lot of work by a lot of  people, over the course of a century, for Chinese hamsters to become the  pharmaceutical powerhouse they are today.

There’s also a bit of serendipity  here: some kids were selling some hamsters in the street that just  happen to have a low chromosome number and a human-like sugar pattern on their proteins. But sometimes, that’s just how science works. Now, when I learn about all the wild things  that come together to build our knowledge of the world, I just want to dive  even deeper into how it all works.

And this is where Brilliant can help. They  have tons of courses and daily challenges, all designed to help you turbocharge  your math and science thinking skills and make sense of this wonderful, weird world. Like their course Knowledge and Uncertainty, which helps us put numbers  on the things we don’t know.

We can never eliminate uncertainty,  but we can learn how to account for it. If you’re feeling ultra-curious, you can  get 20% off an annual Premium subscription, with access to all 60+ courses,  at brilliant.org/scishow. [♪ OUTRO].