In the 1920s, researchers  excavated the long-lost tomb of the ancient pharaoh Tutankhamun.

Infamously, many members of the  expedition met mysterious ends. Their untimely deaths after disturbing the resting  place of a legendary pharaoh have inspired fascination for over a century now, and fueled speculation about a supernatural curse.

Some have speculated that  the cause was not a curse, but a fungus known to be deadly  under the right circumstances. But there’s a twist, because this deadly fungus may  just be due for a redemption arc. [intro] Sorry to disappoint you, but there’s no actual curse on  King Tut’s tomb that we know of. The rumors of a curse started because many of the people  involved in the tomb excavation met untimely ends.

Firstly, and most intriguingly, the financial backer of the  investigation, Lord Carnarvon, died suddenly in 1923, jus t one  year after the tomb was opened. The specific yet distant relationship  between the sponsor and the tomb opening made it seem like Lord Carnarvon’s death was a targeted smite from the pharaoh. After that, several more members of the  original expedition passed away as well, all of which were attributed  to divine retribution.

By 1930, ten people associated with the  excavation of King Tut’s tomb had died. Lord Carnarvon died of an infected mosquito bite, one of the original excavators died by suicide, another was smothered to death, and an unrelated American investor  visited the tomb and died of pneumonia. It doesn’t really matter to the curse narrative that some of the alleged curse  effects didn’t result in death, or that these events sometimes  happened way after the tomb opening.

One of the original excavators  allegedly was injured in a vehicle crash 50 years later in 1970, and even a friend of the lead  archaeologist wasn’t spared: He got a gift of a mummified  hand in a paperweight, and then his house burned down. If any of my friends are watching this  – that is a bad gift. No thank you!

Those misfortunes fueled  feverish speculation by many, including the likes of Sir Arthur Conan Doyle. The famed author of Sherlock Holmes  was a big fan of the supernatural and was quoted in an article  substantiating the curse theory. It’s a compelling story – random Europeans disrupting an ancient  Egyptian pharaoh's resting place and getting smote by the wrath of the dead, and perhaps the gods?

That’s cinema. In a very Sherlock fashion, though, the truth may be much less mystical in nature, and more like “you missed this one  critical detail that ties it all together.” Or, at least some of it. Scientists have checked out the tomb themselves and found some species of a  fungus called Aspergillus.

Aspergillus is a genus of fungus that  causes the disease aspergillosis. It’s quite a common fungus, and you probably breathe some  in every day with no problem. But if you’re immunocompromised  or breathing in a lot of it, Aspergillus can move in and make you sick.

We’ve known about Aspergillus  fungus for centuries, but aspergillosis as a disease didn’t really  get much medical attention until the 1980s. So at the time of the King Tut tomb excavation, doctors likely didn’t even know to look for it. Any of the mysterious deaths that  looked like pneumonia back then could, in fact, have been aspergillosis.

While accurate death reports  are a bit hard to trace, especially with all that talk of a curse, many of the King Tut curse deaths do  seem to be attributed to pneumonia. The other misfortunes are honestly probably  curse-confirmation bias, to be honest Now, this evidence is circumstantial, and nobody has been able to  sample Aspergillus flavus directly from the bodies  of the stricken explorers. It’s reasonable speculation: the fungus was found at the scene of the crime and had plausible means of  carrying out the murder.

But there is one more reason  to point the finger at it. A second series of tomb-related  deaths added further evidence to the fungus side of the debate. In 1973, scientists opened the  tomb of the Polish King Casimir IV, who died in 1492.

Though the dozen scientists were  all healthy before the excavation, 10 of them died shortly afterwards. In the final count, as many as 15 people who had either worked on-site  at the Polish king’s tomb or handled the artifacts  from it fell sick and died.   Once again, a microbiologist  went to the tomb years later and identified the presence of Aspergillus flavus. But, since these findings also  came well after the deaths, we still can’t say for sure that  the people died of aspergillosis, and not something else.

Plus, a lot of the people who died  from the alleged “King Tut’s Curse” clearly didn’t die of a fungal infection, so Aspergillus is not a silver bullet explanation. The lead archaeologist lived  a full life into his 60s, and you’d think he would be  a prime target for a curse. Neither Aspergillus nor a monarch’s wrath can fully explain the series  of unfortunate events.

Still, it’s compelling to  establish that it’s possible that if you go walking into a tomb that’s  been sealed for a while and end up dead, Aspergillus may be to blame. And that’s enough for the fungus’s  reputation to take a bit of a hit. The fungus behind the mummy’s curse?

Nothing good can come of that! …Or can it? We’ll answer that question after this quick break! Since you watch SciShow, you’re no stranger to new ideas.

And this video’s sponsor, Brilliant,  has been cooking up a lot of new ideas. In fact, they’re going all  in on a “new Brilliant.” Now with a visual, interactive  personal tutor for math and coding. It’s all designed to fit into your life  and help everyone be a math person, from fifth graders all the  way to college and beyond.

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And right now, SciShow viewers can save 20% off an annual subscription at brilliant.org/scishow. Scientists are always searching for new compounds that can be used to cure diseases. And nature is a great place to look for ideas.

Lots of safe, useful drugs start out as  or are inspired by natural products – Ozempic, to name just one. In addition, bacteria are constantly  evolving resistance to our antibiotics, meaning we have to stay on  top of creating new ones. So there are multiple reasons to keep  digging into nature’s bag of tricks.

Researchers know that fungi especially are weird little treasure  troves of exciting compounds that could potentially be  used to find new drug options. Fungi… including the one found in  certain ancient monarchs’ tombs. Aspergillus flavus is known to produce  fun little molecules called RiPPs.

RiPP stands for ribosomally synthesized  and post-translationally modified peptide. And that is a lot of words, but that name is basically just referring to how these molecules are made. RiPPs are special molecules that  start out just like any other protein: the ribosomes in a cell string  together some amino acids.

That part's normal. The next part isn’t. RiPPs are different from any other  protein because of how they are finished.

Once the peptide pops out of the ribosome,  it goes through heavy modification by a separate enzyme that can add all  sorts of super complicated structures. Researchers at the University of Pennsylvania became interested in RiPPs because this extremely diverse  set of complex structures also gives them a diverse set of functions. Among those functions are plenty that  are known to act on human biology.

So the scientists decided to go  digging for something useful. Based on previously published literature, the scientists at UPenn decided to comb  through a few different Aspergillus species, looking for one that would be a  good candidate for finding new, useful RiPPs. Using genomic tools, the researchers scanned for  areas of the Aspergillus genomes that might give rise to RiPPs.

Out of the twelve species they looked at, Aspergillus flavus turned out  to be one of the most promising. When they looked deeper at the A. flavus genome, the team found four genes that were likely to code for a  peptide that would turn into a RiPP. The scientists took those four new RiPPs and named them asperigimycins, after the fungus they found them in.

Originally, the researchers were  hoping to find new antimicrobials, to help with that antibiotic resistance problem. While unfortunately the asperigimycins  didn’t show any antimicrobial activity, they did show some anti-cancer activity. Two of the four RiPPs had some  anti-leukemia power, basically as-is.

When the scientists mixed those  asperigimycins with leukemia cell lines, the cancer cells stopped growing. And another one of the RiPPs  showed anti-leukemia activity when mixed with a fatty molecule, with comparable effectiveness in the lab to FDA-approved chemotherapy drugs! They needed to add that  fatty component into the mix to prevent the RiPP from  getting trashed by the cell.

Without that, the asperigimycin couldn’t  get into the proper part of the cell to do its work as efficiently. Interestingly, these asperigimycins seemed  to be specific to stopping leukemia. When the RiPPs were mixed with other  types of cancer cells, nothing happened.

And that’s actually a good thing – that means it can be a promising candidate for developing future leukemia treatments. You actually don’t want your chemotherapy to have a ton of broad effects. You want it to kill what you sent it  in there to kill, and nothing else.

Figuring out why RiPPs work the way  they do can be pretty difficult, but the researchers think that they most  likely flex their anti-cancer abilities by preventing the cancer cells from dividing. Still, this is the very early  stages of this research, and there are likely even more  RiPPs yet to be discovered. The anticancer properties of these RiPPs, and their safety profile for humans, still need to go through a ton of investigation before they can make their  way to real life patients.

At the end of the day, connecting King Tut to this research team’s work was probably mostly a stroke of genius on the part of the university’s media team. And we respect the hustle. Still, it’s very cool that this deadly fungus, maybe responsible for one of  history’s most infamous curses, could be entering its redemption arc.

It’s a reminder that the world is complicated and sometimes the same thing  can be both good and bad. We’re excited to see what comes of the good. [ OUTRO ]