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In this episode, host Hannah Fry is joined by Max Jaderberg and Rebecca Paul of Isomorphic Labs to explore the future of drug discovery in the age of AI. They discuss how new technology, particularly AlphaFold 3, is revolutionizing the field by predicting the structure of life’s molecules, paving the way for faster and more efficient drug discovery.

They dig into the immense complexities of designing new drugs: How do you find the right molecular key for the right biological lock? How can AI help scientists understand disease better and overcome challenges like drug toxicity? And what about the diseases that are currently considered “undruggable”? Finally, they explore the ultimate impact of this technology, from the future of personalized medicine to the ambitious goal of being able to eventually design treatments for all diseases.

Further reading:

AlphaFold 3: https://www.nature.com/articles/s41586-024-07487-w.
AlphaFold Server: https://alphafoldserver.com/
Isomorphic Labs: https://www.isomorphiclabs.com/
AlphaFold 3 code and weights: https://github.com/google-deepmind/alphafold3

Timecodes:
00:00 Intro.
02:11 AI & Disease.
05:30 AI in Biology.
06:51 Molecules and Proteins.
12:05 AlphaFold 3
14:40 Demo.
16:20 Human-AI collaboration.
24:30 Drug Design Challenges.
39:00 Beyond Animal Models.
44:35 AI Drug Future.
46:30 Outro.

Thanks to everyone who made this possible, including but not limited to:

A cure for HIV could be a step closer after researchers found a new way to force the virus out of hiding inside human cells.

The virus’s ability to conceal itself inside certain white blood cells has been one of the main challenges for scientists looking for a cure. It means there is a reservoir of the HIV in the body, capable of reactivation, that neither the immune system nor drugs can tackle.

Now researchers from the Peter Doherty Institute for Infection and Immunity in Melbourne, have demonstrated a way to make the virus visible, paving the way to fully clear it from the body.

A new study published in Molecular Psychiatry suggests that the thyroid hormone system in the brain may be a powerful driver of how fear memories are formed. Thyroid hormone signaling in the amygdala—the part of the brain involved in processing emotions—was not only activated by fear learning, but also necessary for storing fear memories. Boosting thyroid hormone activity strengthened fear memories, while blocking it impaired them. These results may help uncover new treatment pathways for trauma-related disorders such as post-traumatic stress disorder (PTSD).

The amygdala is known to be essential for learning to associate danger with a particular stimulus—such as a tone paired with a shock in laboratory settings. This process, known as Pavlovian fear conditioning, has long been used in animal research to study the brain’s response to threat. Meanwhile, the thyroid hormone system has traditionally been associated with metabolism and early brain development. But it is increasingly being linked to mood, anxiety, and memory. Still, researchers have had limited understanding of how thyroid hormones influence the adult brain’s ability to store emotionally significant memories—especially in brain regions like the amygdala.

Thyroid hormones such as triiodothyronine (T3) interact with specific receptors in the brain called thyroid hormone receptors (TRs). These receptors act as transcriptional regulators: when they bind to T3, they turn on genes that help regulate brain plasticity—the brain’s ability to adapt based on experience. In their unbound state, these receptors suppress gene activity. This dual function makes them a promising target for exploring how hormones can shape emotional learning at the molecular level.

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A team of physicists from the University at Albany has proposed scientifically rigorous methods for documenting and analyzing Unidentified Anomalous Phenomena (UAP) building upon the work of numerous past and present researchers in the field.

The team tested their methods in the field for the first time and reported their findings in Progress in Aerospace Sciences.

UAP is the term used by like NASA to refer to “observations of events in the sky that cannot be identified as aircraft or known .”

Scientists at the Institute for Basic Science (IBS) have uncovered a non-invasive method to boost the brain’s natural waste drainage system—a discovery that could open new avenues for tackling age-related neurological disorders.

In a study published in Nature, researchers from the IBS Center for Vascular Research, led by Director Koh Gou Young, along with senior researchers Jin Hokyung, Yoon Jin-Hui, and principal researcher Hong Seon Pyo, demonstrate that precisely stimulating the lymphatics under skin on the neck and face can significantly enhance the (CSF)—the liquid that cushions the brain and helps remove —through .

This offers a new approach to clearing brain waste using safe, non-invasive mechanical stimulation, rather than relying on drugs or surgical interventions.