You might have noticed that SciShow has done a lot of videos about cancer recently, which is, like, not entirely a coincidence. Being diagnosed with Hodgkin's lymphoma last year has given me some insight into how scary cancer can be, but also how fascinating cancer and its various treatments are.

SciShow has explored these diseases- and cancer is many diseases, not one- from every possible angle: testing, treatment, causes, prevention, even some research on a cancer-fighting gecko named Mr. Frosty. We have gathered these videos together to highlight how much progress we are making in our quest to understand cancer.

I personally found that understanding my disease and my treatment helped me feel more at peace with what I was going through. I went maybe a little further than most would go. This is a selection of books I have read in the last year, for example. I found it comforting, I promise.

We are all gonna deal with cancer in one way or another throughout our lives and I obviously believe that taking it on with careful understanding is the way to go. So here is a very long video with a lot of cancer science.

[INTRO MUSIC]

Chemotherapy sucks.

By all accounts, it’s basically poison. It interferes with stuff in your own cells in hopes that it will kill the cancer before cancer kills you. While it works – and it definitely  works – doctors generally are not fond of putting patients through its gauntlet of side effects.

And they’re actually making steady progress towards not doing that. So here’s a look at why we use chemo,  some of the new options we can use instead, and how cancer treatment is getting better and smarter all the time. 

[INTRO MUSIC]

To be absolutely clear: chemotherapy works. That’s why we use it so much.

At its most basic, chemotherapy, or “chemo” for short, is just using drugs to treat cancer. Between 2013 and 2020, about one in five cancerous tumors in England, that is, more than half a million of the suckers, got treated with some form of chemotherapy.

One thing that’s important to keep in mind is that chemo comes in many shapes and sizes.

There are hundreds of different cancer drugs out there and patients will get one or a combination of different drugs depending on their circumstances. Sometimes the idea is to make their cancer go away completely, while other times the chemo helps to make other treatments like surgery more effective. And sometimes the goal is to simply manage symptoms when a cure isn’t possible.

But cures do happen. Newly diagnosed Hodgkin lymphoma, testicular cancer and acute lymphocytic leukemia can all be treated with chemotherapy with the expectation that in most patients, the cancer goes away — for good. If you want an example that I am intimately familiar with, one common drug is called doxorubicin, which is sometimes combined with three other drugs with similarly difficult to pronounce names into a cocktail called ABVD.

Without going too deep into it, doxorubicin is good at killing dividing cells because normally, the nucleus is a tangled mess of DNA, and it uses an enzyme called topoisomerase as like a molecular detangling spray. The cell needs to detangle its DNA in order to shrink down those neat little chromosomes and divide, which it can’t do without its detangling spray, which doxorubicin blocks. So that’s why doxorubicin targets mostly cancer cells but also can affect other cells that like to divide.

This is a common problem with chemo drugs. We want to target the cancer cells, but the cancer cells, on a molecular level, look very similar to the rest of you. But one thing almost all cancers have in common is that they grow and divide quickly. So a lot of chemo drugs target various growth and division mechanisms. Unfortunately, that means that they can do a fair amount of collateral damage, especially to cells that have to replicate a lot for their normal jobs, like growing hair, replacing the stomach lining, or creating immune cells.

So while I can tell you from personal experience that chemotherapy is miserable, it also has done amazing things for me personally, and I’m extremely grateful for all of the different drugs in ABVD.

But if we can do better, we like doing better!

There are at least two important avenues of research for better, less regular-cell-death-inducing treatments: targeted and personalized therapies. 

Right now, most chemo drugs go in your arm or into your stomach and then everywhere in the body, which is how they get to your stomach lining and hair follicles, et cetera. But targeted therapies are designed to more specifically go after the cancer, leaving the non-cancerous cells alone. Some of these are so-called small-molecule drugs that target different parts of a tumor’s growth cycle. The term refers to small molecules that you would recognize as similar to traditional drugs like aspirin or penicillin. By interfering with molecular processes that only cancer cells have, they can spare a patient some of the harmful side effects of regular chemotherapy.

One of the earliest success stories in this space is a drug called imatinib, which is used for some leukemias. These leukemias have a ridiculously specific mutation known as BCR-ABL. It happens when two different chromosomes get stuck together in one exact place, sending levels of a certain cellular growth signal into the stratosphere. And that mutation is only in the cancer,  not in the patient’s healthy cells. Imatinib shuts that growth signal back down.

This method of stopping messages that are specific to cancer is promising. In fact, a 2018 review estimated about 150 drugs in the same vein as imatinib were in clinical trials, plus countless others that work in other ways. But good small-molecule drugs are hard to make because you need to know a lot about the molecular processes of cancer that you are trying to treat. And then, once you’ve got something that works for one cancer, there’s no guarantee it will work for even a slightly different disease.

Luckily, biology gives us an even better tool for targeting a specific thing. Monoclonal antibodies are another major category of targeted therapy. You may have noticed that a lot of newer cancer drugs have a fancy “-mab” suffix, like trastuzumab, pembrolizumab, and rituximab. These are all monoclonal antibodies.

They come to us courtesy of our own immune system. They are those Y-shaped molecules that normally stick to viruses and other invaders, but with a little science, we can convince them to stick to pretty much anything we'd like. The “monoclonal” bit on the antibody just means all of the ones in a given batch are the same, and stick to the same thing.

In general, monoclonal antibodies do one of three things in cancer treatment: they block cancer cells from growing or flag the cells to the immune system as baddies, or they deliver harmful chemicals into the cell.

Trastuzumab, for example, attaches to a protein found on some cancers called HER2. When cancers have these proteins,  they have a lot of them, and they help the cancer grow and divide. So by blocking them, trastuzumab stops this growth.

On the other hand, pembrolizumab is designed to attach to proteins on your immune cells and super-charge them to better identify and eliminate cancer cells. Since this strategy recruits your immune system, it’s also known as immunotherapy.

Now, another big area of research right now is in personalized therapy. That’s because no two cancers are exactly alike, and no two people have the exact same genetic background. If you have a mutated version of the genes called BRCA1 or BRCA2, you are significantly more likely to develop breast cancer in your life. It’s now way easier and cheaper than ever before to do a test early on to find out if you’re at risk because of your genetics, and then do something about it, either by just being more aware and then screening more often, or by choosing pre-emptive therapy.

More than that, knowing if you have these genes can also impact the best treatment for you if you do develop cancer. For example, a big cancer drug trial published in the New England Journal of Medicine in  2021 found that cancers with BRCA1 or BRCA2 mutations are more susceptible to a type of drug called a PARP inhibitor.

And that’s not all we can do to individualize treatment. In fact, we don’t even need to move beyond breast cancer for another example. Some breast cancers have receptors for estrogen, and some don’t. Those with estrogen receptors respond to drugs that block them, like tamoxifen.

But those drugs won’t work if your cancer doesn’t have those receptors to begin with. The same thing happens with receptors  for progesterone, and also for HER2. We have drugs to target any of the three.

A “triple-negative” breast cancer doesn’t  have any of those three receptors, and tends to be the hardest to treat. On the flip side, though, we  can do tests to find that out, and that can help doctors develop  the patient’s treatment plan. Forewarned is forearmed.

If we can better understand — at a  molecular level — not only the cancer, but also the person it’s growing in, we can use exactly the right  drug in exactly the right place. Chemotherapy is not going anywhere in  the next five, ten, or twenty years. In fact, some targeted therapies just  deliver the exact same old chemo drugs right to the tumor, like a little  side-effect-avoiding Uber driver.

But we’re developing more, better  arrows to have in our quiver, to keep people not only alive but feeling better. And that’s something to feel good about. Chemotherapy is always going to be a balance, but it’s a system we currently have  in place and understand pretty well.

But those drugs won’t work if your cancer doesn’t have those receptors to begin with. The same thing happens with receptors for progesterone, and also for HER2. We have drugs to target any of the three. A “triple-negative” breast cancer doesn’t have any of those three receptors and tends to be the hardest to treat.

On the flip side, though, we can do tests to find that out, and that can help doctors develop the patient’s treatment plan. Forewarned is forearmed. If we can better understand — at a molecular level — not only the cancer but also the person it’s growing in, we can use exactly the right drug in exactly the right place.

Chemotherapy is not going anywhere in the next five, ten, or twenty years. In fact, some targeted therapies just deliver the exact same old chemo drugs right to the tumor, like a little side-effect-avoiding Uber driver. But we’re developing more, better arrows to have in our quiver, to keep people not only alive but feeling better. And that is something to feel good about. 

There's currently no simple way to diagnose cancer.

Cancer is a lot of different things, and there’s just no way to develop one single, straightforward test where doctors prick your finger and a machine goes "yep, that’s cancer!" Except one day there might be, thanks to a gene that doesn’t do anything. 

See, cancer is prone to turning on this one weird genetic sequence that’s widely considered junk. It doesn’t do much of anything for our bodies, even though it does make cancer worse. But one team of researchers is on the trail of this genetic interloper, and by finding it, they think they can find cancer. As in, in general. Here’s how. 

[INTRO MUSIC]

Meet the genetic snippet known as Long Interspersed Nuclear Element 1, or LINE-1 for short. It doesn’t do much. “Junk DNA” is thought to be like stuff that takes up space but has no useful function, and far less of our DNA is “junk” than scientists used to believe.

But LINE-1 takes up space and has no useful function. It’s grade-A-certified spam.

LINE-1 is a retrotransposon – a 6,000-ish-letter sequence of genetic material that replicates by making RNA copies of itself and wandering all over the genome, inserting itself inside strands of DNA. This sequence makes a couple proteins called ORF1p and ORF2p, which have the extremely important jobs of copying the LINE-1 sequence and pasting it elsewhere. And that is all LINE-1 does. Control C, control V. I do want to point out that a molecular biologist calling a protein “Orf1p” is like calling it "Protein McProteinface," as generic as it can possibly get.

This cut-and-paste tomfoolery accounts for 17% of our genome, and yet it contributes absolutely diddly-squat in terms of gene function. Every once in a while an optimistic paper comes out assigning some helpful function to LINE-1, but it’s optimistic. Some researchers have gone as far as to characterize retrotransposons like LINE-1 as genomic parasites- the body just needs a pretty enthusiastic watchdog to keep these things in line.

Transponsons happen in a lot of organisms. Scientists think that at some point there must have been a really good reason for a genetic sequence whose only function was to cut and paste itself. But if there used to be a good reason, it's not super evident now.

Under most circumstances these traveling sequences do nothing but clog up your chromosomes. That’s a big source of stress for cells, and can even cause disease. For instance, if LINE-1 cuts into the middle of a gene, it can break that gene entirely. If a gene is a set of instructions, and you put a totally different set of instructions in the middle of that set of instructions, it’s gonna get pretty garbled. It’s actually been shown that LINE-1 butting in on genes that make blood clotting proteins can break the blood clotting process and cause hemophilia.

As a result, healthy cells don't usually give LINE-1 much opportunity to do its thing, and they silence it in a few different ways, including by attaching chemical compounds called methyl groups to LINE-1 elements. 

This is a common strategy that cells use to turn down genetic material they’re not using. A brain cell doesn’t need to make insulin, right? Leave it to the pancreas. And since nobody needs to make LINE-1, everybody shuts it up.

Here’s the fun thing, though. LINE-1 is allowed to turn back on in about 50% of all human cancers. Researchers don’t really know why, but cancer cells do like to throw away all those little methyl group flags that keep genes silenced. Maybe they just benefit from the chaos. Whatever the reason, LINE-1 in particular nearly always seems to lose its methyl groups, which gives it the ability to turn back on, and the absolutely nothing it does can lead to genetic chaos. Like, in colon cancer, activated LINE-1 is sometimes shown to be stuck in the middle of a tumor-suppressing gene called APC, breaking it, just like with hemophilia.

Other studies show that by inserting itself into DNA, LINE-1 causes a bunch of breaks in that twisty backbone. That compromises the genome’s overall stability, and that damage might aid tumor growth. Research also suggests that LINE-1 expression is related to damage to the tumor-suppressing p53 protein that regulates cell division and suppresses tumor growth in the body.

In other words, LINE-1 can cause an awful lot of mischief for some supposedly harmless genetic junk mail. Just by doing its cut-and-paste thing, it’s tilting the odds in cancer’s favor. Even if a cancer wasn’t looking to turn on LINE-1, so to speak, a cancer that does that just by chance might have a better time.

So it goes that LINE-1 expression seems to be associated with basically half of the cancers, including ones like ovarian and gastroesophageal cancer that are often hard to diagnose because they keep a low profile symptom-wise until they're too advanced to easily treat. Cancers of the esophagus, colon, lung, breast, prostate, ovaries, uterus, pancreas, head and neck all also seem to fire up in concert with the LINE-1 garbage machine.

But here's the amazing thing: it just so happens that if LINE-1 is making ORF1p, one of the proteins that carry it around, it's pretty easy to detect it in the blood.

In a 2023 paper, researchers presented a super-sensitive machine that can look for ORF1p in our blood plasma. In fact, the method works on as little as half a drop of blood! The researchers found the test was extremely accurate in detecting a wide range of cancers. They claim the test itself has a turnaround of just a couple hours and costs less than $3 to produce.

Imagine a procedure no more complicated than the finger sticks used to monitor blood sugar in diabetes. That’s what we might be looking at in the future.

Of course, this test can't tell your doctor where in your body the cancer is hiding – only that ORF1p is present, so you probably got cancer somewhere and more tests are needed. That means it’s a simple, first line screen that’s easy to get to patients, not something to replace more something more sophisticated like a PET scan.

However, this test could also be used to monitor whether treatments are working. If a certain treatment is effective, doctors should be able to see blood levels of ORF1p dropping.

LINE-1 might be a couch-surfing, freeloading, cancer-helping genetic parasite, but its one redeeming quality seems to be that it's not crafty enough to hide its antics. In fact, it may end up snitching on the very cancers it is aiding. Finally, it’s doing something worthwhile. 

Doctors have a huge collection of tools, tests and procedures to diagnose many known conditions. But when something unknown comes up, it’s a race against time to figure out what’s going on. A new condition may affect many people, or just a few. Or in the rarest cases, only one. Yet it’s still important to get them care, even in the most extraordinary circumstances, both to help them, and anyone else who develops the condition, unlikely as it may be.

Which is why doctors and pathologists- the scientists who study disease- had to crack the mystery of the patient with the rarest cancer ever seen; a cancer that as far as we know, has only ever happened once.

The patient was a 41-year-old man in Colombia. And the cancer, technically, wasn’t even human.

The malignant masses of cells in his lymph nodes originally came from a tapeworm. But they didn’t look like tapeworms, or act like tapeworms, so it took about five months for the patient’s doctors in Colombia and researchers from the U.S. Centers for Disease Control and Prevention to puzzle out what was going on.

Let’s look at the case from the beginning. In January 2013, the patient presented with a fever, cough, fatigue, and weight loss. He had been diagnosed with HIV in 2006. There are therapies available to manage HIV infections, but the patient was not taking any medication when he presented. By 2013, the HIV infection had taken a toll on his immune system. This can be measured in two ways: the amount of virus or viral load in the blood, and the number of immune cells called CD4 cells also present in the blood.

HIV destroys CD4 cells, so as viral load goes up, CD4 counts go down. The patient’s viral load was about 70,000 per milliliter, where 100,000 is considered severe. His CD4 count was 28 per cubic millimeter, where below 200 indicates severe infection..

The doctors checked for other infections and found evidence of parasites including Hymenolepis nana, better known as dwarf tapeworm. Dwarf tapeworm is the most common tapeworm infection. It affects about 75 million people around the world, and it has one trick that makes it particularly nasty. Unlike most parasites, which need to live in a couple of different organisms throughout their life cycles, dwarf tapeworms can spend their whole lives, and reproduce, in the human small intestine.

But there was one other thing that caught the doctors’ attention. The man had clumps of cells up to four-and-a-half centimeters across growing in his lungs, his liver, near his kidneys, and in his lymph nodes. In many ways, the clumps seemed a lot like cancer. Under a microscope, the cells in the clump all looked like copies of each other, a sure sign of uncontrolled cell growth. And they were growing in places where they obviously didn’t fit in, much like malignant cancer cells that can spread through the body and take root in new places. Each clump of cells was densely packed and unorganized, like the cells were growing and dividing super fast without any particular function. The cells also had large nuclei, which is common in stem cells, cells that, somewhat like cancer cells, are able to keep growing and dividing. That also pointed toward something malignant.

But the clumps of cells had other features that stopped the team from calling it cancer outright. First, the cells were smaller than most human cancer cells. And when the researchers specifically looked for human cytokeratin and vimentin, proteins that usually show up in human cancers, they didn’t find any.

The researchers started brainstorming; maybe it’s a slime mold, or amoebas, or something infectious, but they ruled those ideas out one by one.

While they ran a DNA test for slime molds and fungi, they received an unexpected result: dwarf tapeworm DNA... with a 99% match. The team double- and triple-checked their results because these cell clumps looked nothing like tapeworms, and they were far outside the tapeworms’ usual territory in the intestinal tract. But remember, the patient did have a tapeworm infection. So the question became: How did it turn to cancer?

A close look at the whole DNA sequence of that tapeworm infection revealed significant mutations in at least five proteins. Three of those proteins had known equivalents in mammals, and those had previously been tied to cancer. So the tapeworm had developed mutations likely related to cancer. And the masses of cells looked like cancer in every sense, except for the part where they were tapeworm cells, leading the doctors to conclude that the clumps were malignant, cancer-like masses that originated in tapeworms.

It took the research team five months to make the diagnosis. But by that time, the patient’s condition had deteriorated. He gave permission for scientists to study his condition and publish the results. Three days after DNA analysis confirmed the diagnosis, he died of kidney failure. It took a few more years for the team to finish analyzing the case and publish their results.

The question remained: How do tapeworm cells spread around a person’s body?

Scientists think that because HIV had depleted the man’s immune system, the tapeworm population in his gut mutated so much that it could move beyond the small intestine. One of the researchers speculated that the masses started out as regular tapeworm larvae. But being in the lungs or lymph nodes and not the intestine that they’re adapted to, they matured out of control into these cancer-like clumps instead of adult tapeworms.

The good news is that the researchers don’t expect this to be a common result of a tapeworm infection. There are effective treatment options available for tapeworm infections, and there are antiretroviral therapies that can lower an HIV infection to an undetectable level for those with access to that care. And while the researchers don’t necessarily expect this to happen again, they do suggest that if it does, it could go mis-identified.

But now that there is a well-documented case, doctors caring for patients in similar circumstances will know to look extra closely at cancer-like lumps. If tapeworms are to blame, then the doctors can start working on the next question: what kind of treatment will help these patients?

Is there anything microwaves can't do? They'll bring your day-old spaghetti back to life, heat up your queso in a matter of seconds. Also, they might help relieve pain and cure some cancers, which is a pretty neat trick as well.

A new technology called microwave ablation is raising hopes that microwaves could soon be used not just to destroy existing tumors, but also to stop new ones from forming in the first place. Mmmm!

[INTRO MUSIC]

Microwaves seem to belong squarely in the kitchen, but they’ve actually been used in medicine for a pretty long time.

And they seem a little bit magic, so here’s how they work. A microwave is a type of electromagnetic radiation, like visible light, or radio waves, or x-rays. It’s got a specific wavelength: from 1 millimeter to 1 meter. Microwaves carry more energy than, say, the 3 meter radio waves that carry tunes for FM radio, but less energy than nanometre-sized x-rays.

And if you can make these waves and then change their direction very quickly, then polar molecules, those with a negative end and a positive end, will try to keep up. Water is just such a molecule, and it gets really agitated in the presence of oscillating microwaves.

But non-polar materials like ceramics, and plastics, and bones aren’t really bothered. This can be annoying when you are trying to reheat something that doesn’t respond well to microwaves, but it will become important later.

Remember that it is only water and other polar molecules that react to these oscillating microwaves.

In the 1920s, magnetrons were invented that could make powerful microwaves, and they were greatly improved in the ‘40s. And that was very useful for applications like radar, but also, it turns out, medicine.

Soon, doctors began investigating how microwaves could be used for healing. And from the very first studies, it was clear that by heating tissues, you could increase blood flow. And that had all sorts of benefits, not least of which was pain relief.

One theory is that increased blood flow increases all the good stuff flowing to the area. Muscles and other tissues love oxygen, nutrients, and cells that specialize in repairing damage. The blood brings all those things right where they need to go. And bonus, the increased blood flow also increases the rate at which bad stuff gets washed away.

And so “microwave diathermy,” the fancy medical term for heating somebody up with microwaves, is sometimes used to treat muscle and bone issues like shoulder injuries, knee problems, and tendon issues. But it’s basically just a way to get heat to an area. It’s the heat that does the healing.

As the technology developed, doctors were able to better target the exact area they needed to. And by using cooling pads to keep the skin cool, they could keep the heat where it was needed without causing damage.

It wasn’t too long until another group of doctors started getting interested in microwaves: oncologists. Sports doctors usually try to keep temperatures in these situations in the low 40s Celsius, because any higher than that and proteins start denaturing and cells start to die. And that, you know, sounds bad. It’s usually bad… unless cell death is what you’re after.

Because cells, of course, tend to be full of water, they are very susceptible to microwaves. But just placing somebody in a giant microwave oven would cook all of their cells, so oncologists have to be a lot more precise. Instead, they insert a tiny probe that creates microwave radiation around the end of the probe. It heats up only the nearby cells and can be very accurately controlled.

This method is called Microwave Ablation (MWA) and it’s gaining traction in oncology as a reliable way to kill cancerous tumors, especially in the liver.

Cutting out a tumor with surgery is probably the most straightforward treatment.  But it turns out that cutting out liver tumors is really hard; the majority of liver tumors are actually inoperable.

That could be for a few different reasons; it might be that the tumor is too close to major blood vessels, because it’s spread too much in the liver already, or because the person isn’t otherwise healthy enough to go through a surgery. The liver is also a common place for cancers to spread to, also known as metastasis, because so much of your blood passes through it on a daily basis.

So here is how microwave ablation for a liver tumor usually works: First, doctors insert a small needle with a microwave antenna at the end into the liver and they guide it directly into the tumor. Then they turn on the microwave generator, and the tip of the antenna causes a field that heats up nearby tissue. By precisely controlling how long the antenna is on and how much power is delivered, the doctors can precisely control how big the affected area gets. Typically, they will aim to destroy the entire tumor and 1cm around it in all directions, just to be safe.

Microwave ablation is effective, and more and more cancer centers are turning to this technology. An even newer advance is the combination of microwave ablation with magnetic nanoparticles. By injecting tiny pieces of material like metals or carbon nanotubes into the tumor first, it can make the microwaves even more effective. Think of it kind of like strategically putting metal in the microwave to get those sparks exactly where you need them.

Another booster for microwave ablation might be the immune system itself. In a study published in 2021, researchers found that the immune systems of patients who had MWA for their early-stage breast cancer actually showed the markers of being better-equipped to fight the cancer.

In another 2020 study in mice, researchers showed that mice with metastatic breast cancer had better survival rates after being treated with microwave ablation than with surgery.

So here’s the theory: in MWA, the charred remains of the tumor are left behind and your immune system is able to learn what the tumor looked like. Compare that to surgery, which totally removes the enemy along with any evidence your immune system can use if the cancer comes back.

For some early-stage cancers, research is starting to show that microwave ablation is a viable option that may be better than surgery. Evidence is mounting that MWA is less invasive, causes less stress on the body, and it can help the immune system.

While microwaves are certainly an exciting avenue of treatment, it’s important to remember that there is no silver bullet for cancer, because it is not just one disease. But for people with certain cancers, this treatment may give an extra edge and save more lives.

Not bad for a technology you probably most associate with a frozen burrito!

Stefan: You may have heard that a major international health policy group has put in place some new warnings regarding artificial sweeteners and their potential to cause cancer. You may also be dragging your diet soda out to the curb.

But before you do that, I'd like to walk you through a little context around this story. Short version: Don't panic. Longer version: This new guidance is based on science, but it's not an open-and-shut case, and some observers say there's a whole 12-pack of issues here.

[INTRO MUSIC]

On July 14th, the World Health Organization added aspartame to a list of things it considers "possibly cancerous," and included a specific warning for liver cancer. We'll get into what that means in a minute, but let's start with the chemical itself.

Aspartame is an artificial sweetener that was discovered by accident in 1968 and has been on the market since 1981. It's used in many kinds of diet soda and other artificially sweetened beverages and foods. Here in the US, the Food and Drug Administration remains convinced aspartame is safe. That said, research into its safety has continued over the years. So, let's get under the hood of this new decision.

Perhaps the splashiest studies arguing against the use of aspartame came out in 2006. This pair of papers from the same research team found that rats that were given daily doses of aspartame had drastically increased rates of cancers of the blood and the nervous system.

But even when these studies were published, other researchers argued that the researchers misdiagnosed what was wrong with the rats.

See, these researchers diagnosed their rats posthumously, conducting necropsies only when the rats died their natural deaths. This isn't the typical way that animal research is done; often, you would raise the animal under the experimental conditions for a set amount of time, and then euthanize them to study. Letting them die of natural causes introduces the possibility that the health issues discovered in the necropsy might have nothing to do with your experiment. And other groups argued that what the team identified as tumors were actually inflammation or signs of bacterial infection in the rats - not cancer.

But even if it was cancer that killed these rats, there's another huge issue with this study, which is just how much aspartame these rats were dosed with every day. Food regulatory agencies like the FDA calculate what a safe daily intake of a given substance might be. The assumption is that the dose makes the poison; even things that could theoretically be dangerous are usually fine in really small doses. So, they define those really small doses and set limits on how much of that thing can be in any food product.

For aspartame, the FDA's safety limit is 50mg/kg of body weight. So, for someone weighing about 68kg (150 lbs) they'd need to consume over 3,400mg of aspartame to exceed that limit. And since a can of Diet Coke contains a little under 200 mg of aspartame, that means you'd need to drink almost 18 cans per day to exceed that threshold.

Some of the rats in this study were given doses of aspartame equivalent to a human consuming 5,000mg/kg body weight, which is astronomically high. It's literally the equivalent of those rats drinking over 26 sodas a day, and not rat-sized sodas, regular 12-ounce ones. In the entire experiment, only two doses of aspartame that these rats are exposed to are below the FDA's acceptable limit. Another study by that same team looked at aspartame's effects on mice, and found that daily aspartame intake was correlated with increased rates of liver and lung cancers, but only in male mice.

Aside from that, it's important to remember that humans are not rodents. So, the next step in figuring out whether aspartame might be related to health risks in humans is to follow a bunch of humans who consume it and just see what happens. And that's what's called a "longitudinal study," where researchers take a large cohort of people, get their baseline data, and follow them over the course of several years to see what changes occur in their overall health.

So, in response to that rat study, in 2006, a team of researchers at the American Association of Cancer Research published the results of their longitudinal study. It looked at adults who consumed varying amounts of aspartame and the rates at which they developed blood and nervous system cancers. The result? There was no correlation between use of aspartame and cancer. And it's important to remember that the study was looking at people who consumed aspartame in a range of quantities. I mean, I've heard of people who drink a dozen Diet Pepsis a day, but that's not most people.

But if these studies came out in 2006, why are we and the World Health Organization talking about this now? Well, it probably has to do with a paper that came out in 2022. Unlike the 2006 cohort study, this one found that consumption of aspartame was correlated to higher risks of breast cancer and cancers related to body weight. And this more recent study found that there was an increased risk of cancers just in general with consumption of artificial sweeteners, which is both interesting and extremely vague. Remember, the new warning is for liver cancer.

And there's one more layer to this artificial sweetener onion; the way that the IARC (International Agency for Research on Cancer) - the WHO's cancer-arm - classifies these risk factors, is not the most intuitive. They have four rankings for how allegedly dangerous something is: carcinogenic, probably carcinogenic, possibly carcinogenic, and not classifiable. But the way that an item gets into any of those categories isn't based on the magnitude of the risk that the thing presents; all that matters is that there's a lot of papers *suggesting* a relationship between cancer and that thing, no matter how small that relationship is.

In fact, in their own words, "The evidence for aspartame causing cancer is limited." And for reference, some things in their "probably cancerous" category include red meat and working the night shift. Like, some of these warnings are simply not practical or feasible to bring into your daily life. Anyone who's ever had a newborn or pulled an all-nighter for school knows that you can't always ensure that a good night's sleep is gonna happen. And those things are in the "probably carcinogenic" pile. Aspartame is going in the one below, the "possibly" group. So, like... eh?

Meanwhile, the WHO also has a food safety committee, and they haven't changed their recommendation on the acceptable limit for aspartame intake; it's still 40mg/kg of body weight, a smidge less than the FDA's.

In any case, figuring out the exact relationship between any single factor and cancer is not easy. And while The WHO may be changing their recommendations, the FDA does not look like they will update guidance here in the US anytime soon.

So, should you throw away all your diet beverages? Well, probably not. I have it on good authority that at least one Diet Cherry Dr Pepper was consumed during the development of this episode. These are decisions that everyone has to make on their own, and bodies like the WHO can only try to provide guidance. So I'll just say it again - don't panic.

Finding a cure for cancer is basically the holy grail of medicine. There have been countless studies aimed at treating different types of cancer, and they've seriously improved the odds of beating this disease.

But one thing that gets a lot less research attention is how to reduce the risk of cancer in the first place. And there’s definitely some evidence for individual strategies to reduce cancer risk. You've heard of some of these, like "don’t smoke."

But in a study published this week in Frontiers in Aging, researchers explored the effectiveness of combinations of prevention strategies. They found that, rather than look for a magic food or behavior that protects against cancer, we might be better off combining multiple prevention strategies.

So far, a lot of the research into individual strategies for preventing cancer has produced mixed results. And where studies do show a positive effect, that effect is sometimes underwhelming, whether due to different study designs or other reasons.

But the international team behind this week’s study thought that the effects might be more significant if some of these strategies were combined. So, they decided to carry out an experiment, with the help of 2100 participants in five different European countries, all of them cancer-free and over the age of 70. For this study, researchers combined three interventions that have some effect on cancer cells, but have had mixed results in prevention studies.

The first was vitamin D. Vitamin D slows the growth of cancer cells by messing with the genes that control cell reproduction and functionality. But in randomized clinical trials, vitamin D doesn’t seem to do much to actually prevent most cancers. At most, it may help prevent advanced cancer and cancer deaths.

The second intervention was a specific kind of omega-3 fatty acid. These nutrients, which can be found in things like fish oil and marine algae, have been shown to reduce inflammation, cell reproduction, and the development of new blood vessels that can feed tumors. But overall, randomized clinical trials show that omega-3 supplements don’t do much either when it comes to cancer prevention.

The researchers’ third intervention was even simpler: exercise. Exercise can decrease inflammation and increase immune system function, both of which could prevent cancer. And many studies have shown that exercise is at least associated with a decreased risk of cancer. But very few have been able to determine whether or not exercise actually causes that decreased risk. That’s because not many have been randomized controlled trials like this one, which are the gold standard for investigating cause and effect. 

So the authors of this study wanted to explore the effect of the three interventions put together. To do that, they divided the participants into various groups. Some groups got just one of the interventions, others got a combination of two or three interventions, and another group got a placebo. 

Participants who were assigned vitamin D and omega-3 supplements took those as pills once a day. The exercise intervention was designed as a simple at-home workout that could be done in the living room. The participants continued with the interventions they were assigned for the next three years. During that time, the researchers checked in every three months to see if any participants had developed an invasive cancer. That’s a cancer that can’t just be cut out of the tissue it developed in. And at the end of the three years, the researchers assessed the overall effect of the interventions on the different groups.

They found that each of the three individual interventions showed a small preventative benefit, but not enough that scientists could be sure it wasn’t just due to chance. On the other hand, in the group that got all three interventions, participants were 61% less likely to have developed an invasive cancer than the group that got the placebo.

These results are exciting, particularly because all of the interventions are theoretically pretty easy. Vitamin D and omega-3 supplements are widely available, though, the quality, purity, and dosage of supplements can vary enormously. And exercise is, well, free, give or take whatever gym memberships you sign up for.

The researchers also claim this was the first randomized controlled trial of exercise as a potential method of cancer prevention, ever. The results suggest that it may be helpful to think about cancer prevention as a combination of strategies that interact to lower your risk, rather than a single strategy that works alone.

But this regimen is not necessarily a silver bullet. While 2100 participants sounds like a lot, once you split them into all the different groups, it’s actually kind of a small study with a couple hundred people per group, which means that the number of cancer cases in general was pretty small. And it’s harder to draw conclusions from small numbers.

It’s also too small a sample size to make any claims about whether this regimen is good or bad at preventing any specific kind of cancer.

Finally, when it comes to thinking about cancer prevention, three years actually isn’t very long. So scientists will need to replicate these results and extend similar studies over a longer period of time to get a better idea of just how meaningful these results are.

But for now, they are promising.

Because, as of today, approximately 40% of people in the U. S. will get cancer during their lifetime. While many of those cases can be successfully treated, cancer is still the second-leading cause of death worldwide. And it costs the U. S. alone around 150 billion dollars a year.

So, any steps that we can take to prevent cancer are incredibly important. And this study gives us a new way to think about just how we might do that.

Mr. Frosty sounds like a frozen summer treat. But it’s also the name of a cancer-fighting gecko! And some people would say that that’s even cooler.

He got his name because of his white and yellow coloring, a special pattern known as Lemon Frost that is encoded in his genes. And these colors make geckos like him very sought after.

But it turns out that his beautiful white pigment is produced by cancerous skin cells. So scientists studied Mr. Frosty and his family and got to the root of some questions about where skin cancer comes from, even in humans.

Researchers at UCLA bought Mr. Frosty from a gecko breeder to figure out how these color-producing cells developed and evolved. And in the process, they were able to figure out some of the genes that regulate the cancer, making those colorful skin cells.

First, they needed to know how many genes make Lemon Frost colors. So the UCLA researchers bred Mr. Frosty with some wild-type geckos to see what their babies would look like. Wild type is the term researchers use to describe a genetically typical animal. About half of the babies were Lemon Frost geckos, suggesting that Lemon Frost is the coloration of a gecko with half wild-type genes and half mutated genes. Then, those Lemon Frost baby geckos grew up and were bred with each other. And the babies from two Lemon Frost parents were about half Lemon Frost, about a quarter had even more white pigment known as "super Lemon Frost," and about a quarter were wild type.

That spread basically means that Lemon Frost likely comes from just one mutation in a single segment of DNA. The researchers also figured out that Mr. Frosty’s Lemon Frost mutation occurs on a gene that makes a ton of white skin cells when it’s mutated.

And that’s the basic idea of some cancers. When cells aren’t properly regulated, your body keeps making more and more of them until it becomes a problem. As you might imagine, geckos that have two copies of the mutation develop even more tumors. Unfortunately, that’s also what makes them stand out with pretty colors on their skin. 

And here’s the thing: You have that same gene that was mutated in Mr. Frosty’s DNA. It’s called SPINT1. Lots of animals have similar genetics, and it’s not always because we’re directly related. Sometimes we have a common ancestor, but other times, we both had similar genetic mutations that allowed us to develop similar physical features. It’s called parallel evolution. And SPINT1 is a gene in humans, as well as in other animals, that determines if you’ll develop tumors or not.

It carries the genetic code for a protein called HAI-1, which stops growth factors. Those are the molecules that usually direct cells to either make more of themselves or not, but HAI-1 stops them from sending pro-growth signals. So if you have cancer cells that won’t stop reproducing, HAI-1 is a part of the process that brings them back into check and signals them to reproduce less.

Scientists think this is one way that SPINT1 reduces cancer. Since HAI-1 is a product of SPINT1’s code, a mutation that changes SPINT1’s code, like what was found in Mr. Frosty’s  DNA, could allow cancer cells to develop. So SPINT1 is likely to be a big player in cancer development and regulation in humans and geckos.

Now, not all geckos with this genetic mutation develop malignant skin tumors, but 80% did in the UCLA study. Which are not good odds. See, if you have a mutation in the  SPINT1 gene, you don’t automatically get cancer, just like if you don’t have it you’re not automatically cancer-free.

One way these genes can become more or less influential is by how often they are allowed to do their jobs. Sometimes, genes can’t produce what they’re supposed to, because there’s something blocking them from making proteins. And if that happens, they end up having less of an impact. So when SPINT1 can’t make its HAI-1 protein to help regulate the production of cells, it can result in cancer. This is what happens to individuals with similar cancers to Mr. Frosty.

Since the SPINT1 and HAI-1 that led to Mr. Frosty’s cancer have also been found in humans, studying Mr. Frosty and his descendants could help us understand where some of our cancers come from and how to stop them from progressing.

We’re all pretty familiar with cold and flu season. But a few decades ago, public health experts began to notice that some non-infectious diseases, like breast cancer, followed a seasonal pattern too.  This 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 behavior 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 flu 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 eleven-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.

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, the seasonality of the hormone might’ve explained 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 secrete 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 seventy 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 will 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.

Medical treatments have come a long way in the last couple of centuries. We now have all sorts of options, from carefully formulated capsules to treatments that harness X-rays. But for all our progress, modern medicine still has a ways to go. Especially when it comes to cancer treatments.

That’s because cancer drugs often target any rapidly dividing cells, which include, but are not limited to a patient’s cancer. That can lead to some not-so-nice side effects like nausea or hair loss. But researchers might have found a way to treat tumors and only tumors by exploiting their love for iron. And they published their findings this week in the Journal of Experimental Medicine.

Researchers were interested in a particularly nasty kind of pancreatic cancer called pancreatic ductal adenocarcinoma, or PDA. Treatments for PDA aren’t that effective right now, partly because tumors start out microscopic in size, making it hard to get the drugs to go there. So having a targeted treatment option would be really helpful.

One way to target cancer cells may be to go after one or several of the mutations that make it different to the body’s regular cells. And that’s what researchers in this study were looking at – a mutation in the KRAS protein. In healthy cells, this protein acts as an important on-off switch for cell growth, where it sends signals to the cell telling it to divide.

Mutated KRAS is stuck in the on position, meaning cells grow out of control, which leads to cancer. But these researchers noticed something else about cells with KRAS mutations - they loved iron. In particular, a relatively reactive form of iron called ferrous iron.

Researchers noticed that genes that controlled iron intake and metabolism were really active in PDA tumors. And that meant that those tumors ended up with lots of iron stored up inside them. The tumors were so chock-full of iron, that the researchers described these tumors as having an “addiction” to the stuff.

Researchers thought they could use the tumor’s addiction against them to deliver anti-cancer drugs directly into tumor cells. They started with a drug called an FeADC – short for ferrous iron-activatable drug conjugate. This is a mouthful, but these do exactly what it says on the tin - they’re inactive until they come in contact with ferrous iron, and then they switch on and release the drug. By linking one of these FeADCs to an already-existing cancer drug called cobimetinib, researchers created a drug that was activated only inside human PDA tumor cells full of iron, and not healthy skin or eye cells.

See, healthy eyes, skin, and gut tissue are often the unassuming victims of these kinds of anti-cancer drugs, so researchers were particularly interested to see if this new drug avoided them. By adding the FeADC to the cancer drug, the drug was essentially switched off until it came in contact with ferrous iron in the tumor. They called the drug combo TRX-COBI.

Next, researchers tested TRX-COBI on different mouse models that had different kinds of KRAS-driven cancers, including PDA but also a kind of lung cancer. And again, the drug slowed down tumor growth, d to when they tried cobimetinib on its own, which affected regular and cancer cells. Plus, the drug did not go after organs that naturally have iron stored up in them, like the liver. That might be because the iron stored there is in an inactive form and so it can’t activate the drug in the same way as the ferrous form. In short, this new drug worked as well as an existing cancer drug but without all the toxicity.

As a final test, researchers tried TRX-COBI together with other anti-cancer drugs. Because, if the drug wasn’t harming regular cells, then maybe patients could handle a more intense burst of therapy to really knock out their tumor. And these combination therapies worked even better at limiting tumor growth in those mouse models, with few side effects on normal tissue. And the researchers think this iron switch could be used with other anticancer drugs too.

Of course, this study was done in the lab and in mice, so it’s not up to human testing quite yet. But hopefully, with more work, it could lead to more effective cancer treatments with fewer side effects down the line.

Cancer loves sugar. So much that it is willing to be sloppy in the way that it makes energy just so it can gobble up more of the stuff. Lucky for us, this flaw is exploitable. We can use a machine called a "PET scanner" to watch where sugar goes in the body, and that can lead us right to a patient's cancer.

Better yet, as scientists learn more about why cancer cells have such a love affair with the sweet stuff, we might be able to develop new treatments, too.

[INTRO MUSIC]

PET is short for "positron emission tomography," and it can help doctors measure a whole bunch of different things, but it's often used to show where in the body cells are turning sugar into energy. It does this by detecting a radioactive substance that has been injected into a patient's bloodstream. One example is really similar to the sugar glucose, and it gets sucked up by sugar-hungry cells. And since cancer cells have the ultimate sweet tooth, they show up as bright blotches on a PET scan.

As you may or may not know, the reason why I keep wearing hats in SciShow videos is that I'm currently undergoing cancer treatment. So I go in for my PET scan, and it's a little freaky! Because they got, like, the thing they're going to inject in your veins in like, a lead-lined syringe to help protect the tech. Because they're, of course, going to get exposed to tons of it working for years as radiation techs, but still! It's a little weird to have something that someone can't touch get injected into your veins. And then, I get the scan back, and it shows me exactly where the cancer is, and I'm like, "Yeah! Radiation in the cancer, that's great!" Then I also see that my brain is glowing like crazy, because the other place that consumes a lot of glucose is up here. [points to head]

So, that's roughly how it all goes down, but if you've had this experience, you might be wondering to yourself like I did, "Why does cancer like sugar so much?" And scientists would love to know that, too, because on the surface, this love affair doesn't make any sense.

See, cells produce and use energy mainly in the form of a molecule called "ATP" (adenosine triphosphate). Most of the time, healthy cells use oxygen to produce ATP from glucose through a series of biochemical reactions called "respiration." Now, respiration actually happens in a series of steps, the first one being glycolysis, where glucose is turned into two of a smaller molecule called "pyruvate" and two molecules of something called "NADH."

Pyruvate can then be broken down further to make energy in one of two ways. First, when there's enough oxygen around, pyruvate undergoes the complex process of oxidative phosphorylation, where the mitochondria convert it into energy. We're going to refer to that one just as "respiration" for convenience to make things easier to follow. The alternative to respiration happens when there's not a lot of oxygen around. You still start with glycolysis, but after that, pyruvate takes an alternative route called "fermentation," where it's broken down less completely for less energy.

Respiration is great because cells can make a lot of energy through glycolysis plus oxidative phosphorylation. Fermentation is okay, too, because cells can still get the energy they need, but it is less efficient. Cells only get around 6% of the energy per unit of glucose from fermentation compared to respiration.

Cancer cells have, for some strange reason, switched most of their energy-making to fermentation, even though there is plenty of oxygen around. They're still doing that first step - glycolysis - and some of that pyruvate goes through the respiration pathway, but somewhere between 56 and 63% of the ATP cancer cells make comes from fermentation. Researchers also call this kind of fermentation "aerobic glycolysis" to point out that this kind of energy-making is happening with oxygen. And since fermentation is less efficient, cancer cells take up more and more sugar to get the energy they need.

There's even a name for cancer's sugar obsession; it's known as the "Warburg effect" after the scientist who discovered it. And although it might seem totally odd, around 70-80% of human cancers get their energy this way. Warburg noted that it might be because the mitochondria - the parts of the cell that carry out respiration - become damaged in cancer cells. But it turns out the mitochondria are not only surviving, they are thriving. Plus, cancer cells aren't the only ones that use aerobic glycolysis; some, but not all, healthy human cells that multiply rapidly do the same thing.

So, researchers think there must be another reason. Now, one theory is speed; aerobic glycolysis is between 10-100x faster at making energy than respiration, which makes up for the fact that the process is so inefficient, providing there's enough glucose to go around. But cells, including cancer cells, have all kinds of other ways of making energy speedily, so it's weird that most cancers would choose this one way. And dividing and growing new cells actually doesn't take that much energy, at least not so much that a cell would need to resort to desperate measures just to make energy quickly.

Another explanation is that cells have other needs than just energy. They also need to make all the stuff that becomes all the parts of a new cell. A dividing cell needs to make more stuff: DNA, proteins, membranes, everything - otherwise, you just get two new half-sized cells.

In 2021, researchers proposed a molecule that I have mentioned here, NADH, might actually play an important part - more specifically, it's counterpart: NAD+. See, NAD+ has many roles in the cell, including helping make all that stuff a new cell needs. But it's also involved in both halves of the energy-making pathway, respiration and fermentation. Remember how I said that after the first step of energy-making, glycolysis, you get a few molecules of NADH? NAD+ and NADH cycle between their two forms by either gaining or losing electrons. And when they do, they help create energy. But at the end of both fermentation and respiration, NADH is turned back into NAD+, so the whole thing can start over again, and the cell can metabolize more glucose.

But for cancer, say the researchers in that 2021 paper, there's a catch. In the process of respiration, the amounts of ATP and NAD+ you get at the end are linked; so if you want to make more of one, you also got to make more of the other. That means if a cell needs more NAD+ relative to ATP - say, if it needs to break down lots of glucose or make lots of stuff - then regular respiration actually isn't the best way to go. Instead, it makes more sense for the cell to use fermentation to get a little more NAD+ back at the end of it.

Now, we did not need to understand the complex biochemistry behind cancer cells' sugar crush to exploit that fact for PET scans, but it might just help researchers develop better cancer treatments. Now, it's not as simple as just not eating sugar; our bodies are really good at getting glucose into the bloodstream, because that's how all of the cells work. This is a bit of a myth of the alternative cancer treatment space based on oversimplifying how all this complicated energy metabolism stuff works. But one idea is to suppress tumor growth by tapping into some of those metabolic pathways and limiting how much of that stuff cancer cells can make.

Of course, like all things cancer, tumors are complex beasts, and there's never going to be a one-size-fits-all answer. But every time we find a one-size-fits-some solution, those people's lives get that much better.

Mantis shrimp have lots of striking characteristics. They have big, rainbow-colored bodies and they punch so strong it can break glass.

But one of their more discreet superpowers is the ability to see polarized light. This might not seem like a huge deal, except that cancer cells interact with polarized light in a unique way. So researchers are developing cameras that can see like mantis shrimp see, and detect very early stages of cancer.

Compared to humans, mantis shrimp have incredibly advanced eyesight that allows them to very accurately scan for prey or potential threats. To start, they have compound eyes, similar to those of a fly. Each eye is divided into three sections that the shrimp can move independently. And, while humans have three different color receptors, mantis shrimp have sixteen. Plus, they have six receptors capable of picking up different kinds of polarized light.

Now, most light sources we encounter, like the sun and light bulbs, emit unpolarized light. Unpolarized light is... messy. It’s made of multiple waves that vibrate in multiple directions, technically planes, at the same time.

But there are a few different ways for light to become polarized, where light waves are vibrating in only one plane - reflecting off surfaces, for example, or passing through something, like polarized sunglasses. And mantis shrimp eyes can detect polarized light.

Researchers believe mantis shrimp evolved this ability for hunting. When light gets reflected off an animal, like a fish with shiny scales, some of it becomes polarized. So, thanks to their unique eyesight, mantis shrimp can accurately spot their unsuspecting prey underwater.

Mantis shrimp can even perceive circular polarized light, a hard-to-see light wave that rotates its plane of polarization in a clockwise or counterclockwise direction.

Mantis shrimp use circular polarized light to communicate within their species. Their bodies have reflective surfaces capable of producing this kind of light, which they flash like a secret message.

Now human eyes can detect some polarized light, but not nearly to the same extent as mantis shrimp, and we can’t distinguish circular polarized light at all. That’s partly because mantis shrimp eyes have more receptors. Plus, all the shrimp's photosensitive bits are stacked on top of each other, and their polarization receptors are oriented in different directions. This makes it possible for the shrimp to intercept light waves coming from multiple directions at the same time and helps them perceive changes in polarization.

Researchers believe these shrimp can even rotate the different sections of their eyes to maximize their detection of polarized light, similar to a person putting on polarized sunglasses to filter a glare.
Polarized sunglasses can block light waves vibrating in one direction while allowing light waves vibrating in another direction to pass through.

So where does cancer diagnosis fit into this already really remarkable story? Could we put a mantis shrimp on someone with cancer and have it punch them in the tumor? No… as cool as that would be. But in their 2017 paper in the journal Optica, researchers from the University of Illinois say they were inspired by the mantis shrimp’s sophisticated eyesight to develop a camera capable of detecting cancer cells very early in their development. In particular, they drew inspiration from the shrimp’s stacked photoreceptors.

In their camera, the researchers stacked multiple silicon photodiodes on top of each other. They combined this with a carefully arranged pattern of metallic nanowires to act as polarization filters. This allows the camera to see in color and detect polarized light coming from different directions, much like the mantis shrimp. That’s key to identifying cancer in its early stages because when researchers aim polarized light at tissues in the body, the light is scattered by the cells.

And they’ve found that healthy cells all scatter this light in a similar way, but cancerous cells do not. That’s partly because fast-growing cancer cells are oddly shaped and irregularly spaced in comparison to healthy tissue. They can also have multiple nuclei and be denser than a healthy cell.

In 2013, researchers studying colorectal cancer proposed that cancer cells can even change the direction of circular polarized light. And the degree to which they change this light’s direction depends on how aggressive that cancer is.

This impact on polarized light shows up very early on, prior to the onset of symptoms or changes that are visible to the human eye. So a camera capable of viewing multiple types of polarized light would be an extremely useful tool for early cancer detection, especially during procedures that require a miniature camera, like a colonoscopy, for example. During this type of procedure, a doctor uses a small camera to spot tissues that look different from healthy tissue. This means the cancer has to be fairly advanced for our feeble eyesight to notice a difference. But the shrimp-inspired camera could improve cancer detection rates during these procedures. In fact, early prototypes used on mice have successfully revealed where healthy tissue ended and cancerous tissue began.

If doctors can use these cameras to find tumors much earlier on, they can use less invasive treatments and decrease recovery times. As an added bonus, this camera is smaller, lighter and less expensive than existing technologies, which means it could be really useful in resource-limited locations.

So one day, these cameras could become a part of your doctor’s toolkit, bringing the superpower of a mantis shrimp's eye to your very colon. 

Not all cancer cells are created equal. Some have mutations in their genes that make them better at getting around treatments like chemo or radiotherapy. Which means a tumor can develop therapeutic resistance, where those treatments don’t work as well anymore. And even just a few cells left over after treatment can turn into another tumor.

But new research might help scientists understand how cancer cells evolve their differences. And that could help them understand and combat therapeutic resistance or develop even more targeted therapies in the future.

In this study, published in the journal Nature in December, researchers looked at acute myeloid leukemia, a type of blood cancer. They tracked cells in three slightly different mouse models of leukemia, where all the mice had been infected with genetically identical cancer cells. Researchers used a technique called SPLINTR, which stands for Single-cell Profiling and Lineage Tracing, to track individual cells. That would let them see which specific cells were doing something different and therefore could become the dominant cells that form new tumors.

SPLINTR works by tagging the DNA of individual cells with sequences of other DNA called barcodes. Those barcodes let researchers see which bits of DNA are actually being used by the cancer cell. The barcodes are also inherited along with the cancer DNA, meaning researchers can also track how the cell evolves by seeing which bits of DNA stick around.

They found that even though all the cancer cells had the same genetics, they behaved differently in different mice. See, different cells can turn on different sets of genes, or use the same genes more or less compared to other cells, even if all those cells have the same DNA. And because turning different genes on means that the cell will make different proteins, cells that might look identical DNA-wise might actually behave quite differently.

In this paper, the researchers were interested in understanding which genes were transcribed in leukemia stem cells. These are the cells that are likely to become the dominant ones and end up forming a new tumor. Researchers saw that leukemia stem cells repressed genes that tell the cancer cell to decorate itself with molecules that the immune system recognizes. Those molecules match up with immune cells that keep cancer under control by killing potentially dangerous cells.

Leukemia stem cells also expressed a gene for a particular tumor growth factor more. Basically, they were better at being cancer-y.

This study is the first time researchers have been able to study how individual cancer cells with the same genes might behave differently. The hope now is that other scientists can use the SPLINTR tool to study other types of cancer because this finding could be really important to the emerging field of personalized cancer treatments. T

There’s a lot of interest in developing treatments tailored to the patient right now, but our ability to do so mostly relies on looking for genetic differences underlying their cancer or other disease. And what this study shows us is that researchers and doctors will have to consider not just a disease’s genetic profile, but how those genes are used as well.

The title of this video does not make sense. There are no single-celled dogs. Dogs aren’t just multi-cellular… they’re vertebrates, mammals even! A single-celled organism is by definition not a dog. And yet… And yet.

Between six and 11,000 years ago, there was a dog. I do not know the dog’s name, I don't even know if it was male or female. But we do know quite a bit about it. It was black or brown with more than a bit of coyote ancestry, and it came from an inbred population, and also, we know it had cancer. And to understand what happened next, and how truly bizarre it is, you have to understand what cancer actually is.

And I know what you’re saying, “Hank, I know what cancer is.” And maybe you think you do! You think that cancer is a disease caused by an organism’s cells malfunctioning and reproducing uncontrollably and moving to different parts of that organism’s body. And that is true, but also, it’s kinda not true. The question is: are the cells malfunctioning, or are they succeeding? And to answer that question, you have to ask another one: why do malfunctioning cells so often reproduce uncontrollably?

Now it’s convenient to talk about evolution in terms of what it “wants,” but evolution doesn’t “want” anything. One school of thought proposes that natural selection is simply successful traits, and their associated genes, succeeding and being passed onto future generations.

And nearly every cell in a dog is trying to help the dog survive. This is what evolution is selecting for at the scale of the dog. Cells work together to keep the animal functioning, so that the genetic material can persist in the current dog, but, more than that, in the offspring of the dog.

But sexual reproduction isn’t the only kind of reproduction. Single celled organisms often reproduce asexually, and natural selection nonetheless still results in evolution in those species, just more slowly. And we can imagine that, inside of a dog, natural selection isn’t just selecting on the scale of the dog; it is also selecting on the scale of the cell.

Natural selection is not a complicated idea. If something can make more of itself, then there will be more of it. If a rat has a gene that allows it to have 1000 babies, then that gene will spread throughout the rat population pretty dang fast.

But if a cell inside an organism has a gene that allows it to have 100,000 or a hundred million copies of itself, that gene will ALSO spread through the organism very very rapidly unless something stops it. And, when that happens… when individual cells inside an organism evolve ways to replicate themselves unchecked, we call that cancer. One way of thinking about cancer is that it is simply the result of evolution acting on the cells of a multi-cellular organism rather than the organism itself.

And this is kind of a hot take, but it’s one that makes sense according to what we know. Cancer cells are evolutionarily successful. Not for the organism, of course, but for the cell.

Seen through this lens, cancer is not an organism’s cells malfunctioning. It is kinda a return to a single celled lifestyle. A step, at least. They still require you as a host organism, and since they usually hurt the host - you - in the process, it’s not a great step. Still, your cells have become more like a pathogen. They have human DNA, but they have started living for themselves instead of for you… metabolizing, replicating, and evolving. So one way to look at cancer is that it is a single-celled organism, with a multi-cellular organism’s DNA.

Now evolutionary pressure on the organism level encourages LOTS of systems for preventing individual cells from growing unchecked because, when that happens, the organism can no longer pass on its genes… because of how it is dead. But evolution at the level of the cell is hard to overcome.

Natural selection is always selecting; genes are always mutating. It only takes one cell being really good at evading the immune system and selfishly replicating itself perpetually for the whole organism to crash. 

Great, Hank, thanks! Wonderful. That’s all very terrifying and upsetting… cancer is the most natural thing ever, and despite the fact that our bodies have evolved a tremendous arsenal of tools to prevent it from killing us, it nonetheless remains an extremely common cause of death. 

But, for the most part, all of this is just semantic line shifting. Is cancer a kind of single-celled organism? Is a hot dog a sandwich? It doesn’t really matter, it’s a deadly disease and it’s not like it’s going to jump off of the sick person and go live on its own.

Unless it does exactly that. Remember that dog that died thousands of years ago? Well, before it died, its cancer managed to spread to at least one other dog, potentially through sexual contact.

These cancerous cells were now a contagious pathogen that, for thousands of years, have been successfully living the single-celled lifestyle.

This disease is called Canine Transmissible Venereal Tumor or CTVT. And you really cannot say that the cells that cause it aren’t…alive. Because they grow, they reproduce, they metabolize, and they evolve. A dog with CTVT does not have a cancer made of its own cells, it has a disease made of cells that are descended from a dog that has been dead for thousands of years. As the authors of a 2014 paper put it, “It is remarkable that a somatic genome whose DNA would normally have survived for no more than 15 years during the life of one dog has continued to exist for several millennia as a parasitic life form. CTVT’s survival and global dominance is a testament to the ability of the mammalian somatic cell genome to adapt and persist in a new ecological niche.”

In other words, this cancer, if you look at it a certain way… is a single-celled dog.

Now the success of CTVT is very weird and unusual. Cancer cells evolve to succeed inside a very particular environment: the body they are a part of. And they evolve to evade the immune system of that one organism. That’s why cancer jumping from one organism to another is extremely rare.

Now, we’re not entirely sure how CTVT did this, but other transmissible cancers have occurred in species that were in population bottlenecks, which just means that their population shrank a lot, and the individuals in that group wound up being severely inbred.

It isn’t difficult to imagine this happening to a population of early dogs. In a situation like this, CTVT would be able to jump from dog to dog because their low genetic diversity might have made it less likely that their immune systems to notice that those cells belonged to somebody else. Given the new evolutionary pressure not just to grow in one organism, but to be transmissible and survive in other organisms, CTVT continued to evolve, and it can now infect not just most dogs, but also related animals like jackals and coyotes!

The fact that there is a line of pathogenic cells, reproducing asexually, descended from an ancient dog that has persisted for millennia is one of the weirdest things that I have ever found out about biology, and it only makes sense to me if you view cancer not as a malfunction, but as a kind of terrible evolutionary success.

Cancer through this lens is a kind of biological inevitability and so we need to see it as a thing that our bodies have developed systems to control and that we can help our bodies control. Evolution allows these selfish cells to evade both our bodies' systems for destroying them, and our technologies for destroying them.

We are in a race, but it is one that we are winning more now than we ever have before.

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