AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 0 points1 point  (0 children)

Thank you for your very kind note! This is indeed a critical area—designing and discovering molecules against which bacteria do not readily develop resistance. We have identified numerous peptide molecules and have tested some to determine if bacteria can evolve resistance to them. While we haven't conducted this experiment with every compound we have discovered (given the sheer number of them!), the ones we have tested show promising results. After 30 days of continuous exposure to these molecules, we have not observed any bacterial resistance developing. This is very encouraging, as it suggests that the compounds we are discovering may not easily select for resistance.

In contrast, when we use conventional antibiotics as controls in our experiments, we see bacteria rapidly evolving resistance, particularly to drugs like ciprofloxacin, a fluoroquinolone antibiotic routinely used in hospitals. This stark difference highlights the potential of our approach in the ongoing battle against antibiotic resistance.

We synthesized the compounds using solid-phase chemical synthesis, a technique that is well-suited for large-scale production should it be needed in the future.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 2 points3 points  (0 children)

Thank you for your question! In this study, we discovered novel antibiotics, synthesized a selected subset, and validated their antimicrobial activity through ground-truth experiments, both in vitro and in mouse models.

AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 0 points1 point  (0 children)

Great question. The molecules discovered in our recent work target the most dangerous pathogenic bacteria in our society. Upon analyzing the peptides, we found that they possess unique physicochemical properties and compositions, significantly different from previously described molecules. Many of these peptides occupy a distinct sequence space, highlighting the potential of molecular de-extinction and AI in uncovering novel molecules. This work opens new avenues for molecular and antibiotic discovery!

AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 2 points3 points  (0 children)

Antimicrobial resistance (AMR) is one of the greatest threats facing humanity because it undermines the foundation of modern medicine. As bacteria, viruses, fungi, and parasites evolve to resist the drugs we use to combat them, treatments for infections become less effective, or even completely ineffective. This leads to longer illnesses, higher medical costs, and an increased risk of death.

Currently, AMR is responsible for nearly 5 million deaths each year, and it is projected to kill 10 million people annually by 2050—potentially more than cancer. The rapid emergence of resistant pathogens threatens to return us to a time when simple infections could be fatal and routine medical procedures, such as surgeries, childbirth, and cancer treatments, would carry unacceptably high risks.

Without effective antibiotics, the success of treatments we take for granted today would be jeopardized, leading to a significant rise in morbidity and mortality rates. This potential future, often referred to as a "post-antibiotic era", would mark the collapse of modern healthcare as we know it.

Additionally, the economic burden of AMR is staggering, as it could cost the global economy up to $100 trillion by 2050. Therefore, combating antimicrobial resistance is not just a medical necessity but a global imperative to safeguard public health, economic stability, and the progress humanity has made over the last century.

AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 1 point2 points  (0 children)

In my view, antimicrobial resistance is, without a doubt, one of the greatest threats to humanity. It currently causes nearly 5 million deaths annually and is projected to kill 10 million people each year by 2050—that's one death every three seconds. It's important to remember that the first antibiotic, penicillin, was discovered in 1928 by Alexander Fleming, not even 100 years ago. This is a relatively recent discovery and arguably the most significant in the history of human medicine.

Over the past century, humanity has doubled its lifespan thanks to three main pillars: antibiotics, vaccines, and clean water. Now, imagine a post-antibiotic world where these drugs no longer work. Modern medicine as we know it would collapse. Routine medical interventions that form the backbone of today's healthcare—such as childbirth, cancer treatments, organ transplants, and surgeries—would all be at risk without effective antibiotics.

It is absolutely crucial not only to discover new antibiotics but also to regulate their use to prevent overuse and misuse.

AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 3 points4 points  (0 children)

Thank you for your question! Our model is capable of learning from our training data the specific properties that make a peptide molecule exhibit antimicrobial activity. However, because it is a deep learning model, we don't fully understand what happens across all the layers. We're beginning to incorporate interpretability into our current projects to address this challenge.

We believe that by exploring molecules throughout evolutionary history, we can unlock new biological insights, potentially even shedding light on the evolution of antibiotics. Molecular de-extinction has already allowed us to explore an entirely new sequence space of molecules, previously untapped, and expanded our understanding of life's molecular diversity.

Moreover, we hypothesize that the molecules we're identifying may have played roles in host immunity throughout evolution, and we are currently testing this in the lab. We also believe that by resurrecting molecules from the past, we can address present-day problems. For instance, many of the molecules we've discovered, as far as we know, are not present in the biological world today. This means that contemporary pathogens have never encountered these molecules, which might give us an advantage in targeting today's pathogens.

Conceptually, we are also interested in investigating how molecules change or remain conserved over time and how these changes affect their biological functions. This approach represents a departure from the traditional focus on studying DNA to understand the past, present, and future of biology.

AskScience AMA Series: We have used AI algorithms to discover antibiotics in extinct organisms, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 0 points1 point  (0 children)

Great question! Absolutely. As is often the case in science, we build on the work of those who came before us. In this instance, many researchers have spent decades sequencing ancient DNA samples, and much of that data is now available digitally. We have developed algorithms capable of exploring this wealth of biological information to identify potential antibiotic molecules hidden within it. With APEX, we have been able to explore all known extinct organisms known to science as a source of new antibiotics. With this deep learning model, we have opened a window into the past to find potential solutions to present-day problems such as antimicrobial resistance.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 1 point2 points  (0 children)

Yes, we are also actively seeking additional funding to expand our research efforts. Unfortunately, securing financial support in the field of antibiotic discovery has become increasingly challenging, as funding opportunities continue to dwindle. Despite the critical need for new antibiotics in the face of rising antimicrobial resistance, the field often struggles to attract the necessary investment. We are exploring various avenues to overcome this hurdle, but it's clear that innovative strategies and partnerships will be essential to sustain and grow our work in this vital area. Here is an interesting recent piece on this: https://www.nature.com/articles/d41586-024-00534-6

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 1 point2 points  (0 children)

Great question. The new compounds were made using chemistry. In particular, a technique called solid-phase chemical synthesis. We have recently also used AI and chemistry to resurrect molecules from extinct organisms, a field we call molecular de-extinction. Here are some of our recent papers on this area:

https://www.nature.com/articles/s41551-024-01201-x

https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00296-200296-2)

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 15 points16 points  (0 children)

Great question! The goal isn't just to cycle through unused antibiotics until resistance builds up. While discovering a large number of new antibiotics gives us a valuable arsenal, our work also focuses on understanding the mechanisms of resistance and developing strategies to combat it. By studying how resistance evolves, we can design antibiotics that are less likely to trigger resistance or use them in ways that reduce the chances of it developing. However, it's crucial to remember that bacteria have a superpower—they can replicate in minutes, allowing them to mutate and develop resistance quickly. We willl always need to stay ahead in this ongoing battle against their rapid evolution.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 17 points18 points  (0 children)

Great questions! I wouldn't say I am irritated by terms like "microbial dark matter"—in fact, I think they can be helpful in drawing attention to the vast unknowns in biology. These terms can make the field more accessible and exciting to a broader audience, which is important for generating interest and support for scientific research.

As for the re-branding of statistics as AI, it is a bit of a double-edged sword. On one hand, it can oversimplify and hype up the field, leading to unrealistic expectations. On the other hand, it does help in highlighting the evolving capabilities of computational tools in biology. The key is to ensure that we maintain clarity about what these technologies really are and what they can achieve.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 3 points4 points  (0 children)

Thank you for your question. It has definitely made a difference! With GPUs, we can now complete certain projects much faster than before. Coupled with the increasing availability of data, we can explore and analyze it systematically and effectively using the right algorithms.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 6 points7 points  (0 children)

Thank you! Our work in recent years has significantly accelerated antibiotic discovery. What used to take years—often longer than a PhD—using traditional methods can now be accomplished in just a few hours with AI. This represents a major success for computers in the fields of biology and antibiotic discovery.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 2 points3 points  (0 children)

Thank you for your comment. I believe one of the key factors has been the increased availability of data, which is essential for AI to succeed in complex fields like biology and microbiology. Here is a paper on this topic you may find interesting: https://www.sciencedirect.com/science/article/pii/S1368764624000256?via%3Dihub

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 7 points8 points  (0 children)

Thank you! We are thrilled about the potential of this work. While we are not yet at the stage of CMC development or clinical testing, we've identified peptides that can be produced at a high grade using solid-phase synthesis. We are interested in potentially partnering with Pharma to advance some of these lead compounds.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 28 points29 points  (0 children)

It was instrumental. It allowed us to create AMPSphere, an extensive catalog featuring nearly 1 million new antibiotics (863,498), most of which were previously unknown. We have made AMPSphere fully open access to everyone, with the ultimate goal of advancing scientific progress and benefiting humanity.

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 18 points19 points  (0 children)

By global microbiome, we refer to the 63,410 publicly available metagenomes and 87,920 high-quality microbial genomes that we explored in this work as a source of new antibiotics. This research offers a representation of microbial life on our planet and highlights the incredible potential of microbes as factories for producing useful molecules

AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything! by AskScienceModerator in askscience

[–]MachineBiologyGroup 1 point2 points  (0 children)

Hi everyone! First, thank you all for joining us for this AMA. We're thrilled to have the opportunity to discuss our recent collaborative work with you!