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You can check them out at linode.com/scishow and that link will give you a $100  60-day credit on a new Linode account. So, say you were getting sick.

Like, I hope that you’re thriving right now,  but let’s just imagine that you got sick, and you went to the doctor for some medicine. You’d hope that the medicine your  doctor gave you was developed carefully and responsibly by scientists studying  the specific disease you have. And you’d be right.

Mostly. Probably. Certainly, by the time a drug gets to  clinical trials, the process is really robust.

But sometimes, at the just-starting-out  level, researchers developing new treatments aren’t actually testing them  on the illnesses they aim to treat. Completely by accident, they are  studying the wrong cells in Petri dishes that have become contaminated. And when other researchers cite that  flawed work not knowing it is flawed, it becomes entrenched.

And this is happening all the time. How could so many researchers  make such a basic mistake? Well let’s explore the answer  to that and how they can fix it. [♪ INTRO] Human cell lines are groups of human  cells that are modified to grow indefinitely and survive outside of a human body.

Think of like every stock video of a researcher peering intently at a Petri dish of pink stuff. There’s probably one on the screen right now. This is what scientists call  cell culture or tissue culture.

The first human cell line was created in 1951, from cervical cancer cells taken  from 31-year-old Henrietta Lacks. These cells were taken without her consent,  and while further discussion of that is outside the scope of this video,  it is also already an excellent book that we will link to down in the description. Now typically, cells only survive for  a few days after they’ve been sampled.

But the cells from Ms. Lacks’  tumor behaved differently. The cells retrieved from  a biopsy were super hardy, and very easy to grow, making them  ideal for researchers to test on.

The doctors found that by  mixing them with blood plasma, they could keep the cell line  going and going, and going, meaning they had a virtually infinite  supply of new cells for experiments. Despite being created over 70 years ago,  the HeLa cell line is still used today, and it’s been central to many  massive medical breakthroughs. Polio vaccines, IVF, our understanding  of cancers, drugs for herpes… just to name a few.

The knowledge gained from deriving HeLa cells allowed scientists to develop more cell lines. With those, they could closely study  and test treatments on other diseases, understand gene functions, create  artificial tissues, and more. In modern labs, cell lines  are a very important tool, because they provide an unparalleled way for us to test things like medicines on  real, complex biological systems.

And having multiple kinds of cell lines, derived from multiple kinds of  tissues, means researchers can choose the one that’s most relevant  to what they’re interested in. Cell lines may or may not be  models of a specific disease, but they're derived from a specific  tissue, so they still work like a tissue. At least, enough to help  understand how that tissue works.

So if you're studying insulin  secretion for diabetes research, you probably want pancreatic cells, for example. Using cell lines also means that you  don’t have to start your research in humans or animals right off the bat. Since the cells are alive and doing cell  things, you can test how they’ll respond in your experiments quickly and easily without  involving any, like, living organisms.

That might, for example, get  you as far as a drug candidate that you can then test in animals and,  if all goes well, on humans later on. And it’s not just drug development. Every detailed little “how does molecule  A work with molecule B” experiment that molecular biologists do probably  needs cell lines at some point, so they’re a huge part of how we  understand everything in biology that’s smaller than a bacterium.

Cell lines are even cost-effective  compared to other techniques, which is always a plus when you’re trying to make your research budget go as far as possible. Researchers can make their own cell lines, or they can buy them from other private  companies or non-profit cell banks. So cell lines are ridiculously useful.

It is not too bold to say that biological research as we know it in the 21st century  would not exist without them. But there is a problem. One that makes cell line research really  difficult for other scientists to reproduce, slowing advances in the field.

Contamination. There are two types of cell culture contamination. The first is by chemical contaminants; things like detergents, toxins,  or the occasional bit of debris.

The second is biological. When they’re inside our body, cells  usually have a whole immune system to protect them from things like  bacteria, mold, and viruses. But isolated in a little dish, infection  can take hold of a cell line culture, damaging them and ruining the whole experiment.

Though it is a pretty common hurdle, good, sterile lab technique can  usually keep this issue at bay. However, the biggest, most problematic  biological contaminant in cell lines is cells. Not the ones that researchers are trying to grow, but other cells from other cell  lines that quietly outcompete and replace the cells researchers  think they are growing.

This is not a new problem. Scientists first noticed  this happening in the 1950s. Researchers began to note that many cell  lines labeled as all kinds of species, from hamsters to ducks, were not.

Instead, they were all  either human or mouse cells. And it did not stop then. HeLa is actually a big culprit  for taking over other cell lines, but it’s far from the only cell line that likes to set up shop where it’s not supposed to.

When a contaminating cell  finds its way into a cell line, by hitching a ride on a glove, from airborne  particles, or otherwise, if it grows faster than the intended cell culture, it can  outcompete and eventually replace it. That’s just because of how things grow. If Cell 1 needs less time to divide than  Cell 2, its numbers are going to double and double again and again faster  than Cell 2, and pretty soon, it crowds out the competition.

And this isn’t the sort of thing that’s  easily spotted under a microscope. Animal cells are typically all  kinds of blobby, so there’s not really an instant visual give-away  that your petri dish has been invaded. Before you know it, you’re  testing your diabetes treatment on a cervical cancer cell line.

Those are different kinds of cells,  with different specializations. Cervical cells were never going to make insulin, though cancer cells admittedly  do do what they want. Even so, you’re barking up the wrong tree.

This is not a rare, isolated issue. It’s global, and it’s persistent. Research has been conducted to try  and piece together just how widespread this issue is, and how much  research from years gone by is probably completely invalidated by contamination.

Some researchers estimate that as many as 18 to 36% of cell lines are contaminated. That is hundreds of millions of  dollars worth of research affected. Research from 2002 found  that the WSU-CLL cell line, which is meant to be a cell line  for chronic lymphocytic leukemia, was actually REH, a cell line derived  from acute lymphoblastic leukemia.

This means that WSU-CLL is mislabeled, and doesn’t reflect what the name says it is. So researchers who think they’re  studying one type of leukemia are actually getting a different one. That might seem like a small difference,  but small differences matter in science.

Different cancers are driven at the  molecular level by different genes, so if you want to find those genes  and understand how they work, you need the right cancer model. Of course, once this oversight was identified, every scientist everywhere  threw out their WSU-CLL cells and moved to an actual model of  chronic lymphocytic leukemia. Except no they didn’t.

Some organizations, like The International  Cell Line Authentication Committee, or ICLAC, are on the case, promoting  awareness to fight this issue. ICLAC followed up on this with a case study, and found that of 27 articles using  WSU-CLL, 24 referred to it incorrectly, seemingly unaware that the  cell line was contaminated. And those 24 articles were  cited a total of 848 times.

And those studies were cited by other  studies in the literature, and so on, meaning studies using the wrong cell line  have become basically accepted as fact. Same for studies using the other 535 contaminated cell lines already identified by ICLAC. Opinions among scientists vary about  exactly how flawed this makes those papers, but most will at least raise an eyebrow.

And researchers are rarely  required to prove that their cells are the ones they think they are. Only some journals, like Nature, ask authors to confirm they’ve checked the  identity of their cell lines. And that doesn’t really do much for the  papers already out there being cited.

The findings coming from these potentially  flawed studies have real world impacts. Clinical trials proceed from evidence  gathered from the cell line studies. A lot of early clinical trials end in failure, so it makes sense to build them  on the best possible foundations.

Otherwise, you risk sending whole  labs of scientists and doctors on wild goose chases for months on end, not to mention the patients who  put their health on the line to volunteer in these studies. A great example of this is INT 407, a cell line originally derived  from intestinal tissue. This cell line is used by many  researchers who look at Crohn’s disease to test treatments and make observations, since Crohn’s affects the intestines, so  it makes sense to use an intestinal model.

Except it’s not intestinal cells anymore. That cell line has been taken over by 

HeLa: the cervical cancer cell line. Vendors for INT 407 specifically  state that this cell line is now indistinguishable from HeLa. It’s no secret. Now that’s not to say that researchers  haven’t made great progress when it comes to Crohn’s  disease, because they have, and we couldn’t find any  clinical trials that specifically said they failed because  someone used the wrong cells.

But a 2021 meta-analysis also didn’t  find any papers referring to INT 407 as cervical cancer, and hundreds  referring to them as intestinal. And maybe it’s just me, but that doesn’t seem like the way we should be studying intestines! So now you see this problem and  you see that it is a big problem.

Where do we go from here? Is all cell line research useless and doomed? No.

Of course not. This problem is frustrating, but  there are best practice guidelines that can help researchers verify  the integrity of their data. The first vital precaution  is making sure researchers get into good habits when handling cells.

That means handling just one cell line at a time, labeling each cell culture with the  name of the cell line and relevant info, like the date it was last used, and  making sure all equipment is sterile. No double dipping with different  samples into the same liquids, discarding used pipettes properly,  cleaning workbenches with 70% alcohol before and after  using them, that kind of thing. But even with all the caution in the  world, contamination can still happen.

And since it’s not typically easy to  spot, we need to get more technological. We need to get more CSI. That’s where DNA analysis,  like STR sequencing, comes in.

STR, or Short Tandem Repeat, sequencing  decodes specific highly-variable regions of DNA called, you  guessed it, short tandem repeats. These are strings of repeated DNA bases. They make up around 3% of the human genome.

These regions are so variable that they  actually differ between individuals. So scientists can use the number of  repeats like a kind of fingerprint. Once the sample has been sequenced, particular repeats can be compared  to a database of cell line DNA.

If the number of repeats in your sample matches those listed against your intended  cell line’s database entry, perfect! That means that the cells in  your cell line genetically match with the cell type  you intended to work with. All is well.

At least for now. Contamination can happen fast, especially in a lab that  handles multiple cell lines, so regular retests are recommended. And this might not work for some older cell lines, since a lot of the original samples weren’t kept.

Still, it’s a good way to make sure that you’re doing the research you think you’re doing. Despite how easy it is to test, though,  many labs and authors elect not to. Perhaps due to lack of funds, lack  of time, or just lack of will, since many journals won’t verify  whether they’ve checked anyway.

But the cool thing about science  is when there is a problem, you can fix it with more science. Admittedly, organizations like  ICLAC are asking researchers to be a little more proactive; just because  no one’s making you check your cells, doesn’t mean you don’t have to. But it’s also pretty cool that  the more we learn about cells, the more we learn about how to use  them to do science responsibly, like knowing there’s a stretch of DNA that can tell you if you’re doing the right experiment.

That helps us keep science reproducible, which is key to making sure that  the knowledge that we have is correct and also to making sure that  anyone, anywhere, can participate. And if we can do that with cell  cultures, which have provided such massive wins for the medical and  biological fields, we all stand to gain. Thanks to Linode for supporting  this excellent SciShow video and thanks to the SciShow team for making it!

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You can access it from all over the place! So Linode has strategically placed data centers that get them closer to where you use the cloud. They’re already a cloud computing powerhouse, but they’re still working to improve  your access to cloud technology by adding at least a dozen more  data centers by the end of 2023.

To get going with those brand new servers, you can click the link in the description  down below or go to linode.com/scishow for a $100 60-day credit on a new Linode account. Thanks to Linode, thanks to all the  scientists for making science happen, and thanks to you for watching. [♪ OUTRO]