A deadly fungus found in ancient tombs could make for a promising anticancer drug.<\/p>\n
Snake venom could be turned into lifesaving antibiotics.<\/p>\n
And extracts from common trees hold promise as therapies for neurodegenerative diseases.<\/p>\n
These are three ways that Philadelphia-area scientists aim to build on the long legacy of scientists who have successfully derived new medicines from natural products. Some estimates suggest <\/b>that 40% of modern medicines<\/a> come from plants, including the most popular prescription drugs.<\/p>\n Scientists would often find these medicines through trial-and-error or even happy accidents. The lifesaving antibiotic penicillin, for example, was identified after mold somehow contaminated a petri dish in 1928. The chemotherapy paclitaxel, used for multiple types of cancers, originated from the bark of the Pacific yew tree.<\/p>\n \u201cNature already made so much stuff for us to explore and then try to learn from,\u201d said Xue (Sherry) Gao, an associate professor in the University of Pennsylvania<\/a>\u2019s school of engineering.<\/p>\n Now, better experimental tools and technological advances are changing the way a centuries-old approach to drug discovery is carried out.<\/p>\n Artificial intelligence has sped up the rate of discovery from years to hours in research conducted by <\/b>Gao\u2019s colleague at Penn Engineering, Cesar de la Fuente.<\/p>\n At Haverford<\/a> College, a scenic campus arboretum has become a laboratory for biology professor <\/b>Robert Fairman\u2019s innovative methods for testing tree extracts in animal models and mapping out how they intercept disease processes.<\/p>\n These scientists see their task as figuring out what lifesaving therapeutics could be hiding in plain sight.<\/p>\n From toxic fungus to cancer drug<\/p>\n Aspergillus flavus doesn\u2019t usually get good press.<\/p>\n This fungus is commonly (and perhaps erroneously) linked to the mythical \u201cPharaoh\u2019s curse\u201d associated with King Tutankhamun\u2019s tomb, without <\/b>strong evidence<\/a> to support that narrative.<\/p>\n It <\/b>is also thought to have caused deadly lung infections in several scientists who entered the tomb of King Casimir IV in the 1970s.<\/p>\n Now, thanks to Gao, its reputation may improve: Her lab turned the fungus into a leukemia-fighting agent.<\/p>\n Many scientists, including her, choose to study this strain of fungi because it\u2019s so common in the environment. Her team started by growing the fungus and then searching for compounds they could harvest from it.<\/p>\n One stood out for its highly complex structure: a compound comprised of seven rings fused together. This type of molecule would generally be linear, Gao explained.<\/p>\n \u201cMeaning it\u2019s very unique,\u201d she said.<\/p>\n It was a new class of compounds that hadn\u2019t been described before. Curious if its abilities could be as special as its shape, they tested it against a variety of targets: bacteria, fungi, and cancer cells grown in the lab.<\/p>\n It proved potent against leukemia cells and had little effect on normal cells.<\/p>\n This desirable duality \u2014 deadly to cancer cells and gentle to healthy cells \u2014 is due to the compound being so big that it can\u2019t enter cells freely. Instead, it needs to be let in by a transporter, a type of protein that acts much like a doorman at the entrance of a building.<\/p>\n Their theory is that leukemia cells contain this transporter at higher levels than normal cells, allowing more of the compound to enter and ultimately kill the cell.<\/p>\n Going a step beyond nature, the team engineered the compound to be even better at entering leukemia cells by adding a fatty molecule to it. This made it <\/b>as effective as two FDA-approved leukemia drugs, cytarabine and daunorubicin, according to results published earlier this summer in the medical journal Nature Chemical Biology<\/a>.<\/p>\n Most exploratory scientific efforts never advance to the point where they are found safe and effective for humans. The next step for this compound will be to test it in animals and eventually move into humans. Even if the results continue to be promising, it could be years before any potential new drugs become widely available to patients.<\/p>\n Many more great medicines are just waiting to be found in fungi, Gao believes. These organisms \u201care so clever to make really complicated molecules,\u201d she said.<\/p>\n For the \u201cmajority of them, we don\u2019t know what their potential even can be,\u201d she added.<\/p>\n Snake venom as medicine<\/p>\n The search for new medicines in nature has traditionally amounted to <\/b>looking for a needle in a haystack.<\/p>\n Scientists dig into dirt, fish samples from the ocean, and grab extracts from random plants.<\/p>\n \u201cIt\u2019s a really painstaking process that can take many, many years, and at the end of the day, oftentimes, does not yield any good candidate,\u201d said de la Fuente, a scientist at Penn\u2019s school of engineering and medical school.<\/p>\n Several years ago, he started using AI to accelerate the process.<\/p>\n He trained algorithms in his lab to recognize qualities that make certain molecules more effective drugs. They search for key patterns at the DNA and protein level, much like a barcode reader scans for specific combinations of black and white bars.<\/p>\n Currently, he is searching <\/b>for novel antibiotics in an unusual source: snake venom.<\/p>\n \u201cVenoms are these evolutionary masterpieces that have evolved through millions of years,\u201d de la Fuente said.<\/p>\n He instructed AI to examine venoms at the protein level and flag any portions that could be deadly to bacteria for the project. This yielded hundreds of candidates within hours.<\/p>\n Of those, researchers <\/b>synthesized 58 in the lab, and found 53 were capable of killing at least one drug-resistant strain of bacteria, without harming human red blood cells.<\/p>\n Their work, which so far has been tested in laboratory models and not yet in humans, was described in a <\/b>July <\/b>article published in the medical journal Nature Communications<\/a>.<\/p>\n \u201cWe are unveiling novel attributes of venoms that might be actually good for humanity,\u201d he said.<\/p>\n In the years prior, de la Fuente\u2019s lab similarly screened for antibiotic compounds across ancient biology, including the genomes of giant sloths, ancient penguins, and other creatures of the past.<\/p>\n His two most promising antibiotic candidates are named \u201cneanderthalin,\u201d found in the genome of Neanderthals, and \u201cmammuthusin,\u201d from the Woolly mammoth genome.<\/p>\n \u201cWe\u2019re actually resurrecting those molecules because they no longer exist in the biological world around us,\u201d he said.<\/p>\n Aging like a tree<\/p>\n At Haverford College, trees far outnumber students. The college campus doubles as both a place of study and a 216-acre arboretum filled with 5,000 trees.<\/p>\n Fairman, who has been teaching biology at Haverford for nearly three decades, is working to prove that these trees could be promising therapeutics for neurodegenerative diseases.<\/p>\n