Seeking 'Superbug' Antibiotics, Scientists Use AI to Synthesize Molecules from Neanderthals (cnn.com) 12
An anonymous reader shared this report from CNN:
The quest for new antibiotics is going back to the Stone Age. The urgency to identify possible candidates has never been greater as the global population faces nearly 5 million deaths every year that are associated with microbial resistance, according to the World Health Organization. A research team led by bioengineering pioneer César de la Fuente is using artificial intelligence-based computational methods to mine genetic information from extinct human relatives such as Neanderthals and long-gone ice age creatures such as the woolly mammoth and giant sloth. The scientists say some of these small protein, or peptide, molecules they have identified have bacteria-fighting powers that may inspire new drugs to fight infections in humans. The innovative work also opens up a completely new way to think about drug discovery.
"It has enabled us to uncover new sequences, new types of molecules that we have not previously found in living organisms, expanding the way we think about molecular diversity," said de la Fuente, Presidential Assistant Professor at the University of Pennsylvania, where he heads the machine biology group. "Bacteria from today have never faced those molecules so they may give us a better opportunity at targeting the pathogens that are problematic today...." The idea to look at extinct molecules came up during a lab brainstorm when the blockbuster movie "Jurassic Park" was mentioned. "The notion (in the film) was to bring back entire organisms, and obviously, they had a lot of issues," De la Fuente said. His team started thinking about a more feasible idea: "Why not bring back molecules from the past?" Advances in the recovery of ancient DNA from fossils mean that detailed libraries of genetic information about extinct human relatives and long-lost animals are now publicly available...
In research expected to publish next year, de la Fuente and his colleagues have developed a new deep-learning model to explore what he describes as the "extinctome" — the protein sequences of 208 extinct organisms for which detailed genetic information is available. The team found more than 11,000 previously unknown potential antimicrobial peptides unique to extinct organisms and synthesized promising candidates... He said that the peptides they discovered displayed "excellent anti-infective activity" in mice.
"Molecular de-extinction offers a unique opportunity to combat antibiotic resistance by resurrecting and tapping into the power of molecules from the past," he said.
"It has enabled us to uncover new sequences, new types of molecules that we have not previously found in living organisms, expanding the way we think about molecular diversity," said de la Fuente, Presidential Assistant Professor at the University of Pennsylvania, where he heads the machine biology group. "Bacteria from today have never faced those molecules so they may give us a better opportunity at targeting the pathogens that are problematic today...." The idea to look at extinct molecules came up during a lab brainstorm when the blockbuster movie "Jurassic Park" was mentioned. "The notion (in the film) was to bring back entire organisms, and obviously, they had a lot of issues," De la Fuente said. His team started thinking about a more feasible idea: "Why not bring back molecules from the past?" Advances in the recovery of ancient DNA from fossils mean that detailed libraries of genetic information about extinct human relatives and long-lost animals are now publicly available...
In research expected to publish next year, de la Fuente and his colleagues have developed a new deep-learning model to explore what he describes as the "extinctome" — the protein sequences of 208 extinct organisms for which detailed genetic information is available. The team found more than 11,000 previously unknown potential antimicrobial peptides unique to extinct organisms and synthesized promising candidates... He said that the peptides they discovered displayed "excellent anti-infective activity" in mice.
"Molecular de-extinction offers a unique opportunity to combat antibiotic resistance by resurrecting and tapping into the power of molecules from the past," he said.
Desperately Seeking Susan (Score:2)
Almost 40 years ago the film Desperately Seeking Susan came out. Now we're desperately seeking superbug antibiotics. Thanks Madonna.
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Scientists looking for ultra-superbug antibiotics (Score:2)
20 years from now on SlashDot.
Can I submit something and add the url later?
Well stop it! (Score:4, Insightful)
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I also feel this way about climate change. Whatever the risks of geoengineering, it's clear that's the only way we're not hurtling straight into a worst case scenario. Because if you believe India et al when they say "Ok, we'll pollute as much as we can for a few decades and then stop, just to make up for the unfairness of you guys getting to", I have a bridge to sell
Why aren't more people concerned about prions? (Score:5, Interesting)
The work in this article is novel, interesting, and important. But something else has been on my mind.
Game and forestry departments have noticed an uptick in chronic wasting disease (CWD) in deer. It doesn't need something macabre like cannabalism to spread. It's not even known how CWD spreads. The sheep prion disease scrapie doesn't need much to spread either. When scrapie is found in a farm, the buildings and land that housed sheep is razed, yet the ground can remain infectious and the disease can return years or decades later [1]. These diseases have not yet jumped to humans despite some hunters unknowingly eating CWD infected meat, but CWD can infect humanized mice [2].
So far, humans don't seem to get prion diseases by exposure to body fluids. But I was surprised to learn exposure happened through cleaned and sterilized surgical instruments. In particular, electrodes were unknowingly used on a patient with Creutzfeldt-Jakob disease (CJD), a prion disease affecting the brain (not to be confused with vCJD which comes from eating infected cows). The electrodes which touched a brain with CJD were cleaned, disinfected, fixed with formaldehyde, then kept in a drawer for some years. When the instruments were next used, two patients died of CJB [3]. This is disturbing as hell because formaldehyde doesn't kill cells in a usual way: it cross-links (polymerizes) proteins so the DNA is bonded and totally dysfunctional. Yet prions, being misfolded proteins, are still infections.
My fear on this is that if a prion arises that can be passed from human to human through multiple bodily fluids, we and all of our progeny will be at risk. Prions have a 100% fatality rate after a years or decades long incubation period, and there is no treatment. Imagine what the world would be like if HIV had no treatment, no sterlization method, and could spread through kissing or sewage. It would get into the oceans. It would get into the ground. It would get into our crops [4] when an unknowingly infected farmer peed in the field.
But no problem, since such a prion disease doesn't currently exist, right? Well it was found that steel wires, when coated in uninfected brain tissue, could catalyze the misfolding of proteins into prions (in cell culture) when inserted in other brains, leading to spontaneous generation of prion disease [5]. My inference is that reuse of surgical instruments can cause de novo prion disease. Prion diseases also arrise randomly in a small percent of people.
I may be thinking wrongly about this, but it looks like we are sitting on a humanity-ending bomb with no knowledge of how much time we have. We need to develop effective detection and cheap treatments that eliminate misfolded proteins before the first human prion epidemic occurs.
[1] https://en.wikipedia.org/wiki/... [wikipedia.org]
[2] https://pubmed.ncbi.nlm.nih.go... [nih.gov]
[3] https://www.scientificamerican... [scientificamerican.com]
[4] https://www.ncbi.nlm.nih.gov/p... [nih.gov]
[5] https://www.sciencedaily.com/r... [sciencedaily.com]
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To reply to myself, I want to be clear that this is speculation. It may be that statistically this scenario shouldn't happen--maybe each part of the scenario is unlikely, and many unlikely things would have to go wrong to lead to an epidemic. Maybe the earth and oceans are so vast that having a long environmental persistence is not a big deal. Maybe (and this is my hope) it's incredibly difficult for prions to get into bodily fluids.
And best of all, I've just read that some people are immune. They have a va
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I agree that prions are scary.
Here is coverage on the topic from a virology professor, part of a virology course [youtube.com] at Columbia University.
And a case study in Texas [virology.ws], and emergency room contamination [virology.ws] causing equipment to be incinerated.
They are basically a single protein from a single encoding gene, with variation among various mammals, with genetic, infectious or sporadic occurrences.
And it has a long incubation period, decades in many cases ...
To me, all this is both fascinating and horrifying.
And it is odd t
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Your comment was not reassuring, lol. But the lecture was interesting. I suspect killing the wolves had more effect on deer prions than our changes to grassland.
I actually don't want to go further into this conversation despite how interesting the topic is, because it could lead to a proverbial "black ball" of Nick Bostrom's Vulnerable World Hypothesis [nickbostrom.com].
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I didn't mean for my comment to be reassuring. ...
It is just a statement of the facts we know
And I do agree with you this is scary stuff, and we can't do much about it. ...etc.
No spraying, no medicines, no vaccines, spontaneously happens,
The saving grace here is that incidence is very low with only several 100s of cases per ~ 330 million. Compare that to a respiratory virus like COVID-19 or flu ...
I still think we don't know certain things about it: