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We’re joined by Dr. Denis Noble, Professor Emeritus of Cardiovascular Physiology at the University of Oxford, and the father of ‘systems biology’. He is known for his groundbreaking creation of the first mathematical model of the heart’s electrical activity in the 1960s which radically transformed our understanding of the heart.

Dr. Noble’s contributions have revolutionized our understanding of cardiac function and the broader field of biology. His work continues to challenge long-standing biological concepts, including gene-centric views like Neo-Darwinism.

In this episode, Dr. Noble discusses his critiques of fundamental biological theories that have shaped science for over 80 years, such as the gene self-replication model and the Weissmann barrier. He advocates for a more holistic, systems-based approach to biology, where genes, cells, and their environments interact in complex networks rather than a one-way deterministic process.

We dive deep into Dr. Noble’s argument that biology needs to move beyond reductionist views, emphasizing that life is more than just the sum of its genetic code. He explains how AI struggles to replicate even simple biological systems, and how biology’s complexity suggests that life’s logic lies not in DNA alone but in the entire organism.

The conversation covers his thoughts on the flaws of Neo-Darwinism, the influence of environmental factors on evolution, and the future of biology as a field that recognizes the interaction between nature and nurture. We also explore the implications of his work for health and longevity, and how common perspectives on genetics might need rethinking.

All the topics we covered in the episode:

Inside every cell, inside every nucleus, your continued existence depends on an incredibly complicated dance. Proteins are constantly wrapping and unwrapping DNA, and even minor missteps can lead to cancer. A new study from the University of Chicago reveals a previously unknown part of this dance—one with significant implications for human health.

In the study, published Oct. 2 in Nature, a team of scientists led by UChicago Prof. Chuan He, in collaboration with University of Texas Health Science Center at San Antonio Prof. Mingjiang Xu, found that RNA plays a significant role in how DNA is packaged and stored in your cells, via a gene known as TET2. The paper is titled “RNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis.”

This pathway also appears to explain a long-standing puzzle about why so many cancers and other disorders involve TET2-related mutations—and suggests a set of new targets for treatments.

Unlocking the complexities of the fruit fly brain is a crucial step toward understanding the human brain. Fruit flies share many genetic similarities with humans, making them a valuable model organism for studying brain functions as well as diseases.

“An estimated 75% of human genes related to diseases have homologs in the fly genome,” Sebastian Seung, co-leader of the research team, told Interesting Engineering (IE).

“We’ve long known about the molecular similarities between fly and human brains. We have been slower to realize that there are also similarities at the circuit level, revealed by examining patterns of connectivity. We now know that fly circuits for olfaction, vision, and navigation have architectural similarities with mammalian circuits for the same functions,” Seung added.

The team says that DNA — known for its stability and density — could be an ideal candidate for MRI data storage.

Brain MRI scans provide invaluable insights into our bodies.


Interestingly, the team successfully encoded 11.28 megabytes of brain MRI data into roughly 250,000 DNA sequences. This translates to a data density of 2.39 bits per base.

The encoded oligos, which are the DNA sequences containing the MRI data, are stored in a “dry powder form.” The oligos weigh only 3 micrograms, which is incredibly small. This suggests that a vast amount of data can be stored in a tiny space.

It can “support over 300 reads under current technical standards.”

The same technique could also be applied to studies of brain damage, Ruetz said. “Neural stem cells in the subventricular zone are also in the business of repairing brain tissue damage from stroke or traumatic brain injury.”

The glucose transporter connection “is a hopeful finding,” Brunet said. For one, it suggests not only the possibility of designing pharmaceutical or genetic therapies to turn on new neuron growth in old or injured brains, but also the possibility of developing simpler behavioral interventions, such as a low carbohydrate diet that might adjust the amount of glucose taken up by old neural stem cells.

The researchers found other provocative pathways worthy of follow-up studies. Genes relating to primary cilia, parts of some brain cells that play a critical role in sensing and processing signals such as growth factors and neurotransmitters, also are associated with neural stem cell activation. This finding reassured the team that their methodology was effective, partly because unrelated previous work had already discovered associations between cilia organization and neural stem cell function. It is also exciting because the association with the new leads about glucose transmission could point toward alternative avenues of treatment that might engage both pathways, Brunet said.

CRISPR-Cas systems help to protect bacteria from viruses. Several different types of CRISPR-Cas defense systems are found in bacteria, which differ in their composition and functions. Among them, the most studied proteins today are Cas9 and Cas12, also known as DNA or “gene scissors,” which have revolutionized the field of genome editing, enabling scientists to edit genomes and correct disease-causing mutations precisely.

Drugs for the K-Ras oncogene inspire an approach for targeting the GTPases, a family of enzymes whose dysfunction can lead to Parkinson’s and many other diseases.

UCSF scientists have discovered how to target a class of molecular switches called GTPases that are involved in a myriad of diseases from Parkinson’s to cancer and have long been thought to be “undruggable.”

Because of their slippery exteriors, the GTPases have remained largely out of reach of modern drug discovery, with the exception of the notorious cancer-causing GTPase called K-Ras.