The Nonverbal Language of Life
And why reading it is the most meaningful challenge in biology
In my past two years at Stanford Medicine, I enjoyed what might be the coolest job on the planet.
You see, there was no formal name for my line of work.
But if I had to pick, perhaps “microbe hunter” would best capture the spirit.
My mission was simple: to explore nature for rare and interesting viruses.
By morning, I’d snap on my gloves and trap viruses in the wild. By night, I’d spin out their DNA, poke them under microscopes, and burn sleepless hours naming each one.
Chasing viruses educated me in many ways—about myself, about microbes, about the immensity of life. But it also initiated me to many of the gaps in modern biology.
And there was one gap in particular that haunted me endlessly.
A Portrait of Modern Sequencing
After isolating a virus, my mission was to sequence its DNA and prove it was unique.
Four days earlier, I’d email my supervisor to send an email to our sequencing company. The sequencing company would then email back, asking for a grant code to cover their fees.
After another email chain with Stanford, the sequencing company finally would send us forms to print out, sign, and store neatly in a ziploc bag with each sample in a fresh container of dry ice.
And only then—after a whole week of seemingly paranormal exercises—could we begin to extract DNA from our viruses, and mail them to a suburban town halfway across the country. All so our data could arrive several weeks after that—in yet another poorly-formatted email.
Were there other ways to sequence DNA? Perhaps, but not without their costs.
We could have bought a DNA sequencer, but even standard machines ran upwards of $100K USD.
Meanwhile, quicker sequencing companies failed to process our viruses entirely—often returning unusable data and wasting weeks of time.
My mishaps with sequencing may have been specific, but they pointed to a much wider flaw.
I couldn’t believe it. DNA sequencing was supposed to be the backbone of biology.
But today’s sequencers resembled mainframes from the 1960s. And any attempt to outsource sequencing felt like a medieval ghost summoning.
After decades of technology, we still didn’t have a world-class way to read biology.
Through my work, I had seen the flaws of sequencing up close.
But when I looked around, no one seemed to care.
That whole week—in class, on my bike, between bites of lunch—I couldn’t think straight. I wondered if I was dense.
Sequencing was the tool of our trade. Surely I wasn’t the first person to notice that it made no sense?
But from deep within, there was another question that clung to me desperately.
What if we sequence DNA anywhere, instantly, for the price of electrons?
And what kind of fantastic future would emerge if we could?
The Labyrinth of Life
As I’m sure you’ve noticed by now, this article was never about virology.
Sequencing DNA isn’t just a chemical exercise. It represents the grandest quest in biology—to lay out the language of life, and to elucidate the rules of our existence.
I’ve always viewed biology as a labyrinth.
As scientists (and as people), we find ourselves standing at the gates of the world’s grandest maze—home to creatures and alchemy that defy human knowledge.
In some sense, the entire history of biology is a record of our first steps into this labyrinth.
We discovered Taq polymerase in a hot spring. We isolated GLP-1 from gila monsters, and rhodopsins from unsuspecting jellyfish. We encountered tardigrades and giant viruses and bacteria that could gobble up rust for food1.
Can you believe it? This is our world!
Life is vast, and it remains painfully mysterious.
Somewhere, deep within the labyrinth of life, is our next generation of brilliant biology. Resting within its walls are answers to humanity’s most intimidating challenges.
If we’ve found so much from feeling in the dark, what if we could illuminate everything?
This is what makes sequencing meaningful.
The labyrinth of life is made from DNA. Reading it is our only path forward, to reach the countless answers that lie within2.
And any effort to improve this process is an effort that nurtures our entire field.
The Stakes of Tools
As a biologist, I will always believe in the beauty of life, and its infinite potential.
If we’ve fallen short, we aren’t being limited by biology. We’re being limited by what we can make and measure.
DNA is the basic unit of life. If we hone sequencing to its limit, biology will bloom into its true potential.
If you read the history of science, you’ll notice a pattern: we tend to separate inventions from the tools that enable them.
We learn, for instance, that William Shockley developed the modern transistor. We learn that Fermi et al. built the first nuclear reactor, and that Virchow and Hooke proposed cell theory.
It’s easy to trace scientific progress back to brilliant scientists.
It’s much harder to see negative space—to appreciate the invisible ladder of tools that science quietly rests on.
We forget that Shockley’s transistor was made possible by germanium chemistry. We forget that nuclear reactors wouldn’t work without control rods, and that cell theory wasn’t even reasonable until the invention of the microscope.
To borrow the words of David Foster Wallace: we are fish, and tools are water.
Tools are transparent, and yet they are the medium through which we observe reality. They quietly decide what is visible and invisible to humanity.
Most biologists find tools boring, and with good reason.
When you work a pipette for long enough, it becomes as familiar and obvious as your own hand. When you sequence DNA your whole life, it’s hard to imagine another way of reading biology.
But this is why I find tools exhilarating—because the right tool can burst open entirely new ways of thinking. Because the right tool at the time can change fate itself.
Talk to (almost) any biologist, and you’ll sense their enthusiasm for the world. It’s a remarkable time to be thinking about life, and we’re all sitting at the edge of a remarkable future.
Reforming sequencing will reform all of biology, and it is what will throw us over the edge.
The New Eyes of Biology
I believe in DNA, and in our reckless, immortal adventure to read life.
I believe that sequencing is the most important problem in biology—one that is downstream of all the questions and answers we could ever ask.
It’s a strange, intoxicating clarity. I’m convinced that there is nothing more meaningful and interesting I could be doing with my time.
So why wait? Why falter?
For the past six months, I’ve embarked on a self-directed expedition through the land of sequencing.
Over nights and weekends, I built a foundation in polymer chemistry, signal processing, and nano-fabrication. I pored over the works of Frederick Sanger, and the lab notes of David Deamer that grew into Oxford Nanopore3.
With pencil and paper, I retraced our history of reading DNA—all the way from ddNTP base termination to single-molecule fluorescent chemistry. And I furiously studied our leading commercial sequencers—right down to their ASICs and flow cells—to learn their systems and design around their faults.
Along the way, I’ve encountered many of the rules and limits that govern sequencing. But I’ve found just as much faulty logic, and just as many assumptions that have gone unquestioned for decades.
My dream is to forge the world’s leading DNA sequencer—with state-of-the-art accuracy, supersonic turnaround, and the best per-base economics that physics allows.
With my background in bioengineering (and my personal stake in sequencing), I’ve developed a working theory on how to make this happen. And with support from OSV and Emergent Ventures, I’m running experiments to ground this mechanism in reality.
Molecules are ephemeral. But life will forever change our universe.
This work may deal with DNA, and perhaps it will grow into much more.
But it will always be an odyssey to make sense of life—to cast our hands a little further into this incredible world.
Maybe something’s wrong with me. I see so much beauty here, and so much potential.
It’s been a while since I’ve felt so alive.
And whatever the journey, I can’t shake the sense that we’re headed someplace exciting.
stay tuned,
- aaryan
Interestingly, these bacteria were first found eating the ruins of the Titanic, landing them the incredible name of Halomonas titanicae
While I base this entire article on DNA, many of my arguments extend to RNA, proteins, and emerging biological polymers. Still, I find it hard to imagine any future for biology without DNA sequencing at its center.
This piece was extremely fascinating, and is worth a read for anyone who hasn’t followed the technical journey of nanopore sequencing.
It's always awesome to feel a deep new calling!!
Who was your seq provider?
Thoughts on https://plasmidsaurus.com/ ?