Curse of the Pharaohs paves way for fight against cancer

For decades, these mysterious deaths were attributed to supernatural forces. But modern science has revealed a more likely culprit: a toxic fungus known as Aspergillus flavus. Now, in an unexpected twist, this same organism is being transformed into a powerful new weapon in the fight against cancer.

Justin Stebbing for The Conversation

Cambridge: In November 1922, archaeologist Howard Carter peered through a small hole into the sealed tomb of King Tutankhamun. When asked if he could see anything, he replied: “Yes, wonderful things.”

Within months, however, Carter’s financial backer Lord Carnarvon was dead from a mysterious illness. Over the following years, several other members of the excavation team would meet similar fates, fuelling legends of the “pharaoh’s curse” that have captivated the public imagination for just over a century.

For decades, these mysterious deaths were attributed to supernatural forces. But modern science has revealed a more likely culprit: a toxic fungus known as Aspergillus flavus. Now, in an unexpected twist, this same deadly organism is being transformed into a powerful new weapon in the fight against cancer.

Aspergillus flavus is a common mould found in soil, decaying vegetation and stored grains. It is infamous for its ability to survive in harsh environments, including the sealed chambers of ancient tombs, where it can lie dormant for thousands of years.

When disturbed, the fungus releases spores that can cause severe respiratory infections, particularly in people with weakened immune systems.

This may explain the so-called “curse” of King Tutankhamun and similar incidents, such as the deaths of several scientists who entered the tomb of Casimir IV in Poland in the 1970s. In both cases, investigations later found that A flavus was present, and its toxins were probably responsible for the illnesses and deaths.

Despite its deadly reputation, Aspergillus flavus is now at the centre of a remarkable scientific finding. Researchers at the University of Pennsylvania have discovered that this fungus produces a unique class of molecules with the potential to fight cancer.

These molecules belong to a group called ribosomally synthesised and post-translationally modified peptides, or RiPPs. RiPPs are made by the ribosome – the cell’s protein factory – and are later chemically altered to enhance their function.

While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi – until now.

The process of finding these fungal RiPPs was far from simple. The research team screened a dozen different strains or types of aspergillus, searching for chemical clues that might indicate the presence of these promising molecules. Aspergillus flavus quickly stood out as a prime candidate.

The researchers compared the chemicals from different fungal strains to known RiPP compounds and found promising matches. To confirm their discovery, they switched off the relevant genes and, sure enough, the target chemicals vanished, proving they had found the source.

Purifying these chemicals proved to be a significant challenge. However, this complexity is also what gives fungal RiPPs their remarkable biological activity.

The team eventually succeeded in isolating four different RiPPs from Aspergillus flavus. These molecules shared a unique structure of interlocking rings, a feature that had never been described before. The researchers named these new compounds “asperigimycins”, after the fungus in which they were found.

The next step was to test these asperigimycins against human cancer cells. In some cases, they stopped the growth of cancer cells, suggesting that asperigimycins could one day become a new treatment for certain types of cancer.

The team also worked out how these chemicals get inside cancer cells. This discovery is significant because many chemicals, like asperigimycins, have medicinal properties but struggle to enter cells in large enough quantities to be useful. Knowing that particular fats (lipids) can enhance this process gives scientists a new tool for drug development.

Further experiments revealed that asperigimycins probably disrupt the process of cell division in cancer cells. Cancer cells divide uncontrollably, and these compounds appear to block the formation of microtubules, the scaffolding inside cells that are essential for cell division.

Tremendous untapped potential This disruption is specific to certain types of cells, so this may in turn reduce the risk of side-effects. But the discovery of asperigimycins is just the beginning. The researchers also identified similar clusters of genes in other fungi, suggesting that many more fungal RiPPs remain to be discovered.

Almost all the fungal RiPPs found so far have strong biological activity, making this an area with tremendous untapped potential. The next step is to test asperigimycins in other systems and models, with the hope of eventually moving to human clinical trials. If successful, these molecules could join the ranks of other fungal-derived medicines, such as penicillin, which revolutionised modern medicine.

The story of Aspergillus flavus is a powerful example of how nature can be both a source of danger and a wellspring of healing. For centuries, this fungus was feared as a silent killer lurking in ancient tombs, responsible for mysterious deaths and the legend of the pharaoh’s curse. Today, scientists are turning that fear into hope, harnessing the same deadly spores to create life-saving medicines.

This transformation, from curse to cure, highlights the importance of continued exploration and innovation in the natural world. Nature has in fact provided us with an incredible pharmacy, filled with compounds that can heal as well as harm. It is up to scientists and engineers to uncover these secrets, using the latest technologies to identify, modify and test new molecules for their potential to treat disease.

The discovery of asperigimycins is a reminder that even the most unlikely sources – such as a toxic tomb fungus – can hold the key to revolutionary new treatments. As researchers continue to explore the hidden world of fungi, who knows what other medical breakthroughs may lie just beneath the surface?

(Justin Stebbing is a Professor of Biomedical Sciences, Anglia Ruskin University)