Life Is Geometry

In 2025, we’ve got DNA all figured out, right?  It’s been over fifty years since Crick and Watson (and Franklin) discovered the double helix structure. We know that permutations of just four chemical bases (A, C, T, and G) allow the vast genetic complexity and diversity in the world. We’ve done the Humam Genome Project. We can edit DNA using CRISPR. Heck, we’re even working on synthetic DNA. We’re busy finding other uses for DNA, like computing, storage, or robots. Yep, we’re on top of DNA.

Super-resolution imaging reveals the 3D geometry of the genome. Credit: Northwestern University

Not so fast. Researchers at Northwestern University say we’ve been missing something: a geometric code embedded in genomes that helps cells store and process information. It’s not just combinations of chemical bases that make DNA work; there is also a “geometric language” going on, one that we weren’t hearing.

Wait, what?

The research - Geometrically Encoded Positioning of Introns, Intergenic Segments, and Exons in the Human Genome – was led by Professor Vadim Backman, Sachs Family Professor of Biomedical Engineering and Medicine at Northwestern’s McCormick School of Engineering, and director of its Center for Physical Genomics and Engineering. The new research indicates, he says, that: “Rather than a predetermined script based on fixed genetic instruction sets, we humans are living, breathing computational systems that have been evolving in complexity and power for millions of years.”

The Northwestern press release elaborates:

The geometric code is the blueprint for how DNA forms nanoscale packing domains that create physical "memory nodes" — functional units that store and stabilize transcriptional states. In essence, it allows the genome to operate as a living computational system, adapting gene usage based on cellular history. These memory nodes are not random; geometry appears to have been selected over millions of years to optimize enzyme access, embedding biological computation directly into physical structure.

Somehow I don’t think Crick and Watson saw that coming, much less either Euclid or John von Neumann.

Coauthor Igal Szleifer, Christina Enroth-Cugell Professor of Biomedical Engineering at the McCormick School of Engineering, adds: “We are learning to read and write the language of cellular memories. These ‘memory nodes’ are living physical objects resembling microprocessors. They have precise rules based on their physical, chemical, and biological properties that encode cell behavior.”

“Living, breathing computational systems”? “Microprocessors”? This is DNA computing at a new level.

Electron microscopy resolves a 3D packing domain— the physical “memory node”
of the human genome. Credit: Northwestern Engineering

The study suggests that evolution came about not just by finding new combinations of DNA but also from new ways to fold it, using those physical structures to store genetic information. Indeed, one of the researchers’ hypothesis is that development of the geometric code helped lead to the explosion of body types witnessed in the Cambrian Explosion, when life went from simple single and multicellular organisms to a vast array of life forms.

Coauthor Kyle MacQuarrie, assistant professor of pediatrics at the Feinberg School of Medicine, points out that we shouldn’t be surprised it took this long to realize the geometric code: “We’ve spent 70 years learning to read the genetic code. Understanding this new geometric code became possible only through recent advances in globally-unique imaging, modeling, and computational science—developed right here at Northwestern.” (Nice extra plug there for Northwestern, Dr. MacQuarrie.)

Coauthor Luay Almassalha, also from the Feinberg School of Medicine, notes: “While the genetic code is much like the words in a dictionary, the newly discovered ‘geometric code’ turns words into a living language that all our cells speak. Pairing the words (genetic code) and the language (geometric code) may enable the ability to finally read and write cellular memory.”

I love the distinction between the words and the actual language. We’ve been using a dictionary and not realizing we need a phrase book.   

I recently read about, and was impressed by, something called MetaGraph, a tool developed at ETH Zurich to search DNA databases. "It's a kind of Google for DNA," as Professor Gunnar Rätsch, data scientist at the Department of Computer Science at ETH Zurich, puts it. This “DNA search engine” makes it much easier, faster, and cheaper to search for DNA sequences and compare them to other sequences. Cool as that is, the existence of the geometric code means that the ETH Zurich folks may have some additional work to do, as is true of lots of other people working with DNA.

I hate to say it’s a whole new ball game, but there certainly are some important new rules.

The presence of this geometric code has implications for our health. It may not always be DNA mutations that cause problems; our DNA structures may sometimes be falling apart. Dr. Almassalha says: “Instead of a puzzle of genetic words, the geometric code lets cells build elaborate tissues, such as brains or skin. But with age, this language loses its fidelity. This decay results in neurodegeneration, cancer, or other diseases of aging.”

This opens up all sorts of new avenues for research, and, potentially, treatments. “The next step is to fully learn the engineering principles of the geometric code so we can repair dysregulated cell memories or create entirely new ones,” Professor Backman says. “Current approaches to aging try to reset cells back to a factory default state. The geometric code works differently. Cell memories are physical structures enhanced by experience. Revitalizing cells resembles restoring the clarity of a well-loved book — bringing back the stories our cells already know how to tell.”

This isn’t CRISPR. This isn’t mRNA. This is a new way of thinking about cells and our genome. This is a whole new step in computational biology, and it may be foundational in 22^nd century medicine.

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If you are a physics or cosmology buff, you may have heard the expression “The universe is geometry.” E.g., Einstein’s general theory of relativity indicates gravity is not a force but, rather, the result of distortions in spacetime. Similarly, whether the universe is flat (Euclidian), positively curved (spherical), or negatively curved (hyperbolic) has profound implications for the fate of the universe. In fact, some scientists believe that geometry may explain everything from the smallest particles to the universe itself.

So it pleases me to think that life itself may owe much to geometry as well.