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Tag: DNA

Life Is Geometry

By KIM BELLARD

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.

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.

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.   

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A New Future for DNA

By KIM BELLARD

As a DNA-based creature myself, I’m always fascinated by DNA’s remarkable capabilities. Not just all the ways that life has found to use it, but our ability to find new ways to take advantage of them. I’ve written about DNA as a storage medium, as a neural network, as a computer, in a robot, even mirror DNA. So when I read about the Synthetic Human Genome (SynHG) project, last month, I was thrilled.   

The project was announced, and is being funded, by the Wellcome Trust, to the tune of £10 million pounds over five years. Its goal is “to develop the foundational tools, technology and methods to enable researchers to one day synthesise genomes.”

The project’s website elaborates:

Through programmable synthesis of genetic material we will unlock a deeper understanding of life, leading to profound impacts on biotechnology, potentially accelerating the development of safe, targeted, cell-based therapies, and opening entire new fields of research in human health. Achieving reliable genome design and synthesis – i.e. engineering cells to have specific functions – will be a major milestone in modern biology.

The goal of the current project isn’t to build a full synthetic genome, which they believe may take decades, but “to provide proof of concept for large genome synthesis by creating a fully synthetic human chromosome.”

That’s a bigger deal than you might realize.

“Our DNA determines who we are and how our bodies work,” says Michael Dunn, Director of Discovery Research at Wellcome. “With recent technological advances, the SynHG project is at the forefront of one of the most exciting areas of scientific research.” 

The project is led by Professor Jason Chin from the Generative Biology Institute at Ellison Institute of Technology and the University of Oxford, who says: “The ability to synthesize large genomes, including genomes for human cells, may transform our understanding of genome biology and profoundly alter the horizons of biotechnology and medicine.”

He further told The Guardian: “The information gained from synthesising human genomes may be directly useful in generating treatments for almost any disease.”

Professor Patrick Yizhi Cai, Chair of Synthetic Genomics at the University of Manchester boasted: “We are leveraging cutting-edge generative AI and advanced robotic assembly technologies to revolutionize synthetic mammalian chromosome engineering. Our innovative approach aims to develop transformative solutions for the pressing societal challenges of our time, creating a more sustainable and healthier future for all.”

Project member Dr Julian Sale, of the MRC Laboratory of Molecular Biology in Cambridge, told BBC News the research was the next giant leap in biology: “The sky is the limit. We are looking at therapies that will improve people’s lives as they age, that will lead to healthier aging with less disease as they get older. We are looking to use this approach to generate disease-resistant cells we can use to repopulate damaged organs, for example in the liver and the heart, even the immune system.”

Consider me impressed.

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The 2024 Word of the Year: Missense

By MIKE MAGEE

Not surprisingly, my nominee for “word of the year” involves AI, and specifically “the language of human biology.”

As Eliezer Yudkowski, the founder of the Machine Intelligence Research Institute and coiner of the term “friendly AI” stated in Forbes:

Anything that could give rise to smarter-than-human intelligence—in the form of Artificial Intelligence, brain-computer interfaces, or neuroscience-based human intelligence enhancement – wins hands down beyond contest as doing the most to change the world. Nothing else is even in the same league.” 

Perhaps the simplest way to begin is to say that “missense” is a form of misspeak or expressing oneself in words “incorrectly or imperfectly.” But in the case of “missense”, the language is not made of words, where (for example) the meaning of a sentence would be disrupted by misspelling or choosing the wrong word.

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DNA is Better at Math than You Are

By KIM BELLARD

I was tempted to write about the work being done at Wharton that suggests that AI may already be better at being entrepreneurial than most of us, and of course I’m always interested to see how nanoparticles are starting to change health care (e.g., breast cancer or cancer more generally), but when I saw what researchers at China’s Shanghai Jiao Tong University have done with DNA-based computers, well, I couldn’t pass that up. 

If PCs helped change the image of computers from the big mainframes, and mobile phones further redefined what a computer is, then DNA computers may cause us to one day – in the lifetime of some of you — look back at our chip-based devices as primitive as we now view ENIAC.

It’s been almost 30 years since Leonard Adleman first suggested the idea of DNA computing, and there’s been a lot of excitement in the field since, but, really, not the kind of progress that would make a general purpose DNA computer seem feasible. That may have changed.

At the risk of introducing way too many acronyms, the Chinese researchers claim they have developed a general purpose DNA integrated circuit (DIC), using “multilayer DNA-based programmable gate arrays (DPGAs).” The DPGAs are the building blocks of the DIC and can be mixed and matched to create the desired circuits. They claim that each DPGA “can be programmed with wiring instructions to implement over 100 billion distinct circuits.”

They keep track of what is going on using fluorescence markers, which probably makes watching a computation fun to watch. 

One experiment, involving 3 DPGAs and 500 DNA strands, made a circuit that could solve quadratic equations, and another could do square roots. Oh, and, by the way, another DPGA circuit could identify RNA molecules that are related to renal cancer. They believe their DPGAs offers the potential for “intelligent diagnostics of different kinds of diseases.”

DNA tracking DNA.

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DNA Storage in a Yottabyte Era

By KIM BELLARD

Did you know we are living in the Zettabyte Era? Honestly, did you even know what a zettabyte is? Kilobytes, gigabytes, maybe even terabytes, sure, but zettabytes? Well, if you ran data centers you’d know, and you’d care because demand for data storage is skyrocketing (all those TikTok videos and Netflix shows add up). Believe it or not, pretty much all of that data is still stored on magnetic tapes, which have served us well for the past sixty some years but at some point, there won’t be enough tapes or enough places to store them to keep up with the data storage needs.

That’s why people are so keen on DNA storage – including me.

A zettabyte, for the record, is one sextillion bytes. A kilobyte is 1000 bytes; a zettabyte is 10007. Between gigabytes and zettabytes, by powers of 1000, come terabytes, petabytes, and exabytes; after zettabyte comes yottabytes. Back in 2016, Cisco announced we were in the Zettabyte Era, with global internet traffic reaching 1.2 zettabytes. We’ll be in the Yottabyte Era before the decade is out.

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First, Do Net Harm?

Recently, the US Preventative Services Task Force reiterated its recommendation that women not undergo routine screening for ovarian cancer. This was remarkable, not simply because it was a recommendation against screening, but because the task force was making the recommendation again, and this time even stronger.

The motivation for the recommendation was simple: a review of years’ worth of data indicates that most women are more likely to suffer harm because of false alarms than they are to benefit from early detection. These screenings are a hallmark of population medicine—an archetypal form of medicine that does not attempt to distinguish one individual from another. Moving beyond the ritualistic screening procedures could help reduce the toll of at least $765 billion of wasted health care costs per year.

We already know the common changes in the DNA sequence that identify people who have higher risk of developing ovarian, breast or prostate cancer and most other types of cancer. Consumers can now readily obtain this information via personal genomic companies like 23andMe or Pathway Genomics. But we need to do much more DNA sequencing to find the less common yet even more important variations—those which carry the highest risk of a particular cancer. Such research would be easy to accomplish if it were given top priority and it would likely lead to precision screening. Only a small fraction of individuals would need to have any medical screening. What’s more, it will protect hundreds of thousands of Americans from being unnecessarily harmed each year.

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