Biological technology: A secret world of magic
and mere ideas on how to build it
This is a sensorial experience. Tune in by clicking on each title’s link.
Carbon and oxygen were dancing, making fire. Around them sounds were orchestrated by a choir. Long before the silicon empire, these elements had already inspired The Sapiens, reinforced by energetic motion. The Sapiens, inventing locomotion. In alchemizing their potions they lost all precautions. Waltz turned into watts, science opaqued arts. Carbon off the charts, dopamine-addicted rats. Alien sentience-lacking intelligence willed by Earthians' irrational quintessence. A world of magic, the most profound of all desires. Now that agency affairs with tetrels, magic is for the makers.
I wish there was a secret world of magic…
Harry Potter, Narnia, The Lord of the Rings, The Mysterious Island, and Alice in Wonderland were among the first books I ever read. They used to make me feel something that the ‘real’ world never could. Eventually, however, they became dissatisfying in my quest for new answers about our world, so I turned to tech and science. I fell for Apple, became obsessed with biotech.
The choir sings that any sufficiently advanced technology is indistinguishable from… I not only believe that MAGIC exists. I think that you and I can make magic and humanity’s future depends on more people joining us. I think that human progress is a function of us taking action to fulfill ours and other’s desires.
People, technology, magic. This piece of text is a collection of ideas: on why to better develop human capital in the biological tech industry, what kinds of new technologies we could make to enter a virtuous cycle of bio creation, and what a not-so-secret world of bio magic might look like afterwards (spoiler: beauty).
The world is dying for magic. It’s about time you choose to come see it with me.
People: from Blackberries to Bananas
“In certain oases, the desert is merely an illusion”—Mario Benedetti.
“Progress in science depends on new techniques, new discoveries and new ideas, probably in that order”—Sydney Brenner.
Setting the bio scene
I like the first quote better but thought that you’d unfortunately be more reluctant to listening to an Uruguayan writer. Luckily, you’re not gonna question a fellow life scientist and Nobel laureate, are you?
It is him who is questioning you.
Why did you get upset about that 10-min Zoom update before being teleported to the other side of the world, yet stood a whole day-long argument to get your LCMS1 to even respond?
Why did you submit that grant proposal that chatGPT helped you write in seconds, before spending months debugging your DNA code in those cells you claim to know?
Did you just press a button to watch any out of thousands of Netflix shows, to forget for just a moment that you’ve settled down for using that single ‘oldie-but-goodie’ promoter for most of your work? Excusing yourself saying that this is what your PI has always done?
And you make a side-hustle posting TikToks just to stop hearing the tic-tac of the clock that will soon tell you “another day, another gel… another hell”.
Stylus and keyboard included, these… are biotech’s Blackberry days. If we’re lucky…
The soil that nurtured Apple trees
In clear contrast to bio, computer scientists of the 50-60s were in not much hurry to heal disease or feed the world. They were, however, aligned to build computers that landed rockets and won wars by performing increasingly more complex computations, increasingly faster and more efficiently.
Winning war is a powerful forcing function. World War II saw significant investment in computers like the ENIAC, that solved military calculations. While still made out of vacuum tubes, this machine was among the first demos of the feasibility and potential of electronic components for large-scale numerical computation.
In hindsight, the ENIAC’s greatest limitations included its size (roughly ~167 m2 of floor space), memory (limited to 20 ten-digit decimal numbers), and most importantly, being programmed manually by rewiring and switching cables — triple yuck!
To jump from vacuum tubes to transistors, from Blackberries to Apples, we did not make new tools to wire and switch cables, a new keyboard or new styluses. We changed “the cables” themselves. From vacuum tubes to transistors, from punch cards to keyboards. New media not only improved efficiency but also changed how programming was done all-together, allowing for more modular and abstract languages. What Sidney missed in his quote is the people who decided to work on those tools.
Please, watch this 3-min video before proceeding. It’s all about the people and their choices to pursue a big, bold mission.
Biotech’s forcing functions
I do like to think that the COVID pandemic was a force of sorts. Billions of mRNA vaccines shipped in less than 2 years, including one made by biohackers in Ukraine and the US who streamed it on YouTube, AlphaFold reaching 95% confidence, minIONs used all around the world in all sorts of ways, a new wave of climate startups, the Ultima $100 USD genome, CRISPR curing a girl with leukemia for the first time, Doudna and Charpentier winning the Nobel Prize, DAOs as a new scientific funding model, Biden’s bioeconomy executive order, bio Substacks and Netflix series enriching pop biotech culture. It almost felt like we were “back”.
Just like the ENIAC, these developments happened to be accelerated by pandemic events. Unlike WWII, problems didn’t end with the pandemic. No Nobel Prize has helped more than half of the world's population who lack access to essential healthcare. The billions of funding going to climate startups haven’t stopped CO2 emissions from rising. While some strive for eternal life, more than 1 billion people remain obese and nearly 1 billion hungry. Despite the millions of citations related to it, cancer still killed 10 million people worldwide in 2020 alone.
Our current biotech workforce managed to fight a global pandemic. Will it be enough to solve all the other problems?
A permisionless biotech culture
Here, please watch this other < 2 min video of some friends and I interviewing Eric Schmidt (former Google CEO) at Synbiobeta in 2022. His advice for our industry supports my ideas and makes them more credible — Thanks Eric!
How did we get such amount of bio done despite the world going online for months? People connected by the magical and positive force of the internet. Not in spite of it. Because of it.
It’s in Isaacson’s Code Breaker book: each one of biotech’s big Ws during the pandemic was possible because the world’s biotech workforce united to do so over zooms and google docs. Zooming in, however, we are very likely upon a biotech workforce supply shortage.
The President’s Council of Advisors on Science and Technology recently found that “U.S. biomanufacturing capacity is not keeping pace with both the workforce needed to meet the demand to scale up new bioproducts and the biomanufacturing infrastructure necessary to move products to pilot scale production. This has led some entrepreneurs and companies to move to Europe or Asia to begin scaling up production.”
I bet Niko McCarty a banana that at least 30% of the readers here will be US-based AND either first or second-generation immigrants. They understand that we have not been living in human capital scarcity yet the demand side has been terrible at discovering and developing the gems of global human talent.
Ramanujan is the epitome of a genius whose world-changing work wouldn’t have been fulfilled if it hadn’t been because he cold-wrote math profs, one of whom brought him over to Cambridge. Today, organizations like Open Philanthropy, Emergent Ventures, RISE, the Foresight Institute, and the Thiel Fellowship, are founded solely on the mission of finding the next generation of thinkers and makers and supporting them economically to do great work. We’re getting better at talent discovery.
As for developing the talent we have, I see the problem is not in the number of PhDs (nearly 15% of bio workforce) but rather that bachelor degrees are either not leveling up with industry demands or industry is remaining too ‘credentialistic’. We all know it, someone needs to say it, it ought to be faced: biotech education needs also needs an update.
Patrick Collison (Stripe) learned to code at 10 and sold his first tech startup at 19 for millions of dollars. No one was there to say “Hey, wait! You need to get a PhD first” and if there was, he could afford not listening and selling his company to someone else. Every techbro knows this2: Evan Spiegel (SnapChat), Ritesh Agarwal (OYO), Sam Altman (now OpenAI), Mark, Steve, Bill, Elon, Sergie and Larry. They all started as nerds playing with their computers.
This is not about the whole scandal of the young dropout founder. Permisionlessness happens when even young people have the tools to make something people want, at the tip of their fingers. It is about the culture created by the infrastructure: Maye buys Elon a computer, he gains skills, makes a videogame, sells it, goes on to do much bigger stuff.
As one of the movement’s most fervent leaders, Jo Zayner thinks of biohacking as quite a fluid term that includes doing science outside of traditional institutions. Her company, The ODIN, sells biohacking kits online to enable anyone to do CRISPR and recombinant DNA experiments on bacteria, plants, and even human cells.
If you ask me, Edward Jenner, who invented the first vaccine ever in a rural English village in the 18th century, was a biohacker. Jane Goodall's self-funded study of chimpanzees in the 20th century revolutionized primatology and was great science done outside of traditional institutions yet not necessarily biohacking. Gregor Mendel, who became the father of genetics by breeding peas and analyzing them, was a 19th century monk and a biohacker in his own way too. As our toolkit expands so do our biohacks. (More on this shortly…)
The heaviest weapon that folks (including the FBI) point with at companies like The ODIN and people like Jo is not bioethics but biosecurity. “Fear of randos making bioweapons in their kitchens” seems to be the general sentiment. Biohackers’ response is something like “Randos with way deeper pockets may already have them and I don’t want the rest of the world, including me, to be their pray”.
Let’s take a look at the real enemies. Even with advances in sanitation and access to healthcare, current technological, demographic and climate changes have influenced the surge of more than 40 new infectious diseases such as SARS, MERS, Ebola, chikungunya, avian flu, swine flu, Zika and SARS-CoV-2, since the 70s.
As much as atoms are local, let’s not forget that biology has no borders. Previously mentioned pathogens originated in countries like China, Uganda, and Mexico and yet, the economic and social impact of at least one of them was global. It is thus imperative that we forge strong, international biosecurity agreements, in addition to each country’s (like the US and China have done).
Suggesting what these specific biosecurity agreements should entail is hard for me (probably most) at this point. In this, an essay of ideas, I will say that global biosecurity should be agreements and technology that enable everyone to play with biology without destroying others or the planet. We’ve learned how to play with fire without burning ourselves or others, it’s time to do the same with bio.
It’s of hackers and governments to understand that this is more than just an interesting debate. As I see it, it’s an intense social, economic, and environmental guerrilla on who has access to bio tools and the permission to use them for good: a biologization of democracy, as someone I know would say.
Tech: providing every scientist with exceptional tools
Right now, I could buy a musical instrument, download some mixes to GarageBand, post it on YouTube or Spotify and become the next Jacob Collier. I could buy a 3D printer and re-make all the objects in my house, take a 20-hour course and build a useful app for the world. The fact that I can doesn’t mean I will.
Unless there’s something like a zombie apocalypse because of our bad biosecurity measures (lol?), I don’t see my 50-year-old hippie auntie using a home bioreactor to grow her groceries and a vaccine. The kitchen bioreactor’s market will not live long but the market for affordable and intuitive industrial bioreactors will. Anyone who wants to use it should be able to do as Jacob.
In a 1990 interview, Steve Jobs said “The Computer is the bicycle of the mind”. He understood that we, as humankind, are tool builders. We create technology that expands our physical and mental capabilities, that makes us move, feel, and think different. Sofia’s version goes something like “While art is in the eye of the beholder, science is in the beholder’s lens”.
In our era, the mind is becoming its own bicycle. From optical microscopes (physics tech) to sequencing by synthesis (mostly bio tech), biology is understanding itself. Each new technology is a step towards increased self-awareness. To imagine a new lens, I’ll tell you 2 more short stories.
The first one took place in Drew Endy’s office: “What’s more complex, the cellphone on your hand or one of the bacteria cells surrounding them?” he asked to me once upon a time. I immediately answered “the cell”. As anyone who knows Drew would imagine, he went on to describe what cells would look like if only they were human-scale.
What if a chromosome was as tall as a human, a ribosome was a golf ball, the whole cell the size a building and the cytoskeleton well, the actual scaffolding of the building? (Or something near that).
The next short story is about Steve Job’s hero, Edwin Land, the founder of Polaroid. Even though he had invented his first camera 25 years prior, one day his daughter asked him why she wasn’t able to see the pictures she took instantly. This inspired Land to build the Polaroid SX-70.
The film itself already contained all the necessary chemicals that would react when exposed to light, developing the image in a matter of seconds. This magic was put into people’s hands thanks to Edwin breathing and building at the intersection of science and art, physics and photography.
These days, each of the omics serve like a one-dimensional registry of a cell’s environment. Bio technologists process samples and prepare libraries in a manner akin to photographers before the 70s. It’s somewhere between the spectrum of Sci and Fi, passing through taboo, to conceive of a device that could take a plant leaf or human saliva just as it is, and capture its multi-dimensional (all-omics), color picture, just like a Polaroid, just like Drew imagines cells.
BerkeleyLights devices quite literally shed light on the cells you are looking for, in days instead of months. They continuously image individual cells (human, soon fungi and others) on a microfluidic chip, measuring phenotypic and genotypic data at the same time. That plus, near-real time cryo-EM might be getting to a V1 NanoPolaroid.
Imagine seeing every single thing that happens inside a cell. To be able to zoom in to transcription of a gene, translation of a protein codon by codon, zoom out to see a cell dividing in two, watching a movie of cells differentiating into other cells. Automating the analysis all of that biophysical information and going “huh, so my gene needs one more NLS to make it in” or “cells with such diameter can absorb CO2 10x better!” I don’t know… there’s plenty of room at the bottom ;)
Understanding human desires can be deceiving. Every business freshman knows that Apple does not sell phones, they sell status. Starbucks doesn’t sell coffee, they sell an experience. “Where’s my flying car?” concerns engineering as much as it does psychology. Innovation gives people what we want and not what they expect. Hence we wanted flying cars and got Zoom and Facebook instead.
In the history of biological research, one could only go as fast as biology can grow. After paying close attention to the ball that biotechnologists love to hit3, we shall build innovations, beyond AlphaFold, that are zooms and not faster horses, that will elevate the experience of doing science without interfering with the feeling for the organism.
Among the most ambitious quests I can think of, is making a virtual cell. A conversation with a leader of the Microsoft StationB team left me thinking whether the map can ever be the territory, whether the best model of the cell we have is the cell itself. I guess similar questions have been made in relation to our universe, and to us, cells are still a whole universe.
Cell Atlases are what the Chan-Zuckerberg Biohubs are working on these days. What if you could fuse all the omics stack with cryo-EM and who knows what else (bioelectricity maybe?) to understand health and disease, at the single-cell level, for every single human cell, from your computer? They’re kind of funding different research groups to make that happen, and open-sourcing the tools to accelerate global biotech efforts.
Biohacking doesn’t have to be limited to culturing bacteria in your kitchen. GarageLab (not so hypothetical invention) allows (young) scientists to run hyper-realistic bio simulations. You can just see at what beat (rate) your favorite gene is produced given X much sugar at X temperature to X cell. You can just turn on X microbial ion channel and make a symbiosis with X tree cell that is 89% differentiated. You can visualize how each growth media component or a genetic switch like BitBio’s leads to any cell. You can grow anything, online, for real. It’s on the cloud and it’s collaborative, just like a Google Docs (better). Then let the robots or other scientists make it. Looks like Asimov bet me to it ;)
Next step is doing that for tissue engineering too! My mom loves kitting and follows these strange-looking patterns that transform into jaw-dropping sweaters. Programming live tissues just as she ‘programs’ threads would be cool. Though this has been tiredly proposed by biopunks, it seems as though research in bioelectricity by the Levin lab might be bringing it to life in the coming years: programing ion channels to program shape, to program function? This starts to sound like architecting life, more on that soon…
“Life is ultimately an electrochemical enterprise” — Michael Levin
Magic: /imagine A secret world of (bio) magic
Biology has something that no other technology will ever have. The connection we feel towards our loved ones, the awe we experience when seeing something amazing like a bioluminescent cave, the pleasure of smelling a flower then tasting its fruit, touching skin, the delight of hearing a bird sing. These things we don’t buy (at least we did not use to). Biology is an open-source, magical experience. Today’s biological technologists will expand that beyond the confines of current imagination.
(Bio) Discovery kit
You know the tech nerds going with those electronic kits everywhere? I want to be a bio nerd with a bio portable kit. The main limitation to current ones is mostly modularity. Yes, biology just grows and you can make more DNA out of the one you have, and more organisms too. I shall answer in another post why synthesis is lagging behind and thermocyclers, even miniPCR’s are as expensive as some phones. Let’s make any organism be as shippable as seeds — they’re like Zip files!
Oxford Nanopore’s minION is magical. It fulfills the desire for long-read, accessible and portable sequencing. Yet in writing the future of biology, computer scientists may have developed a better scribe. One that we all know by now.
What if instead of having to sequence the whole realm of nature’s proteins, we could simply hallucinate existing and better ones? BioGPT would take us from a bioGoogle (browsing across millions of gigabytes) to one in which we simply ask for what we want.
I dream of a world in which I can prompt a chatGPT-like entity to design a new fruit of my choice and have it grown at my nearest local bioreactor facility (much like computer servers). A breed between a banana, a guava and mango - my favorite fruits. Fruit is awesome. Evolutionary, artistic, delicious. The perfect dessert does exist and it’s called FRUIT! 😍 🍌 😍 🥭 😍 🍓
AgroNT is a foundational LLM that can obtain predictions for many genomic elements, including polyadenylation sites, splice sites, open chromatin and enhancer regions by using. It can predict the strength of promoter sequences and tissue-specific gene expression levels or prioritize functional variants.
Avalo has built a patented AI platform to identify regions associated with traits of interest, create a digital genotyping panel and optimize breeds through insilico evolution faster. The goal is to develop crops that are richer in flavor, more robust towards changing climate, and packed with nutrients… at a 100x lower cost!
(Bio) Twitch and YouTube
Creators often become creators after being inspired by other creators. The Thought Emporium has been gaining some traction on his bio videos over the years, some Latch guys have even done bioinformatics livestreams, and Jason Carman has started a fantastic collaboration with Petri to film short stories of the awesomest biotech startups out there. We need more. Way more.
Like, watching TikToks of PhD students explaining papers is nice but it’d be way cooler to have something like Cleo Abram of biotech. Share something exciting every single day, something that people desire and care about. Lab visits to places that “makes textiles while eating CO2” or “program DNA barcodes to track food”. Think the comeback quirky sci shows that make stuff and explain it to you, except it’s cool and everyone loves it. Discovery h&h for bio or whatever. Just freaking make bio sexy.
For everyone, not just kids. Telling stories of bio should not only inspire the next generation of bioengineers but also tear down the walls in front of every non-scientist that reads “wtf is a GMO in the first place, how do I eat it and how is it made?!”.
(Bio) Toy Story x Night at the Museum
Now, to change the 6-year-old dream job from firefighter to bioengineer, you need to quit Jurassic Park and make a bio Toy Story — sorry Ginkgo guys! What this statement is really calling for is getting closer to people who wouldn’t have heard about biology otherwise.
Meet Jimmy, a micropipette that hangs out in the lab bored until someone assigns a special mission to him: to be the leader of a biological revolution by designing and making new and more nutritious food ingredients to feed and shelter the bottom billion in a sustainable way.
Jimmy sets out to accomplish this mission when he realizes that he’s missing an essential plasmid. He and his friends, bacteria and plants, need to fight mammalian cells that make fun of them and their scientists who want to throw them to trash because they don’t see their value.
After a series of losing friends in a centrifuge, almost getting burnt in a thermocycler, and following the advice of an ancient plant as a mentor, they manage to make a biofactory of playful and useful solutions for the world.
(Bio) Book of the Dead
“The adaptations of an animal, its anatomical details, instincts, and internal biochemistry are a series of keys that exquisitely fit the locks that constituted its ancestral environments — they’re a key to reconstruct the environment they were in. If we could read the genome appropriately, we could get a negative imprint of ancient worlds, a description of the ancestral environments of the species: the genetic book of the dead”— Richard Dawkins has published a new book!
We often think of biotechnology as the future of our species, forgetting the countless unrecognized humans that have safeguarded nature to bring us to this moment. That sounds utterly romantic, but it’s not only new fragrances that we can get by studying extinct species, but also new approaches to biomedicine.
In a present that has been shaped by silicon-driven globalization, I call for carbon-driven localization. Biology shall not only scale organisms but scale cultures: Carbon Valleys.
I urge you, dear reader: don’t write a book about your roots. Don’t make a TED talk on your festivities and traditions, don’t post Instagram stories about the dishes your grandma used to make for all your family as a kid, don’t wear the custom you used to wear in that far away place, oh PLEASE don’t dare to remind me of the music that makes you vibe or reminisce on the scents that are still on your mind.
Show. Me. Ins-tead.
No, better yet: SHOW THE WHOLE. FREAKING. WORLD. INSTEAD.
Show us how to make those colorful clothes, from the organisms that create the textile to those that synthesize the dye. Share with us the exact herbs you use for that tea you drink at sunrise. Teach us what a great spice should actually taste like. Oh please do enlighten us with the natural sounds from your backyard.
Do not only engineer biology. Architect it. That means to follow the principles of architecture: beauty, utility and durability. Inspired by Swiss-French architect and designer Le Courbusier in his book Towards a New Architecture, I think we should start seeing biology like an artistic pursuit, a means of expression, a way to feel:
“You employ stone, wood, and concrete, and with these materials you build houses and palaces: that is construction. Ingenuity is at work. But suddenly you touch my heart, you do me good. I am happy and I say: This is beautiful. That is Architecture”.
(Bio) Network states
Some months ago, the hottest bio and crypto celebrities joined in Monte Negro to discuss and imagine the future these two fields could create when united. I wished they would’ve shared more. Technology like Ethereum, combined with the internet, are starting to enable people to found whole nations. Biotechnology is enabling us to grow anything from saffron to brains, anywhere in the world, independently of climate conditions.
If folks are already putting their genetic info on the blockchain, could we one day mine and trade any specie’s genome just as we mine bitcoins? Like, BCoin, proof of sequencing, anyone? Of course, the idea of assigning a different piece of DNA to a block might become obsolete as we can hallucinate such sequences.
So invite the economists and urban planners to the party! Allow them to help us figure out how to integrate or adapt one thousand biofactories into our existing infrastructure. Invite the technical crypto guys to implement safer cyber infra for all our data. We’re need them all.
Life’s last issue: dedicated to the people who made it
The writing challenge that I created this post for believes in the power of writing and sharing your ideas. I too acknowledge that writing has been one of the most accelerating forces in my career. Looking back at my first article on synbio, I’m glad to know that both my writing and my understanding have improved a significant bit too.
After writing about 100 pieces throughout 3 years, I’ve come to strongly believe that the best stories are not written in paper or Substacks. The best stories are built and created, they are sensorial experiences, stuff you can touch and interact with, and use to make other people’s lives better. They are grown and evolved. From computers to trees, each product tells a story. More so in the age of non-biological intelligence, we hold on to our feelings to keep… feeling human.
My last biodream is to store everything. Everything I ever did and thought, created and built, into DNA. Get every single part of my body sequenced, EEG’d, CT-scanned and cryo-EM’d. Transfer all my digital data from the cloud, all my writings and photos and conversations, into a seed I plant before I die. I wish for everyone’s right to do that too.
Our genes are the trees under whose shade we don’t sit; keepers of ancient secrets and stories. You and I, the whole universe, is the forest of our past. Who knows, maybe we’re the story someone else has written in the purest language they could find: life. I wonder what tales our seeds will tell the future after we’ve turned biological technology into a not-so-secret world of magic…
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I don’t think we need a similar troubleshooting guide for our smartphones or computers these days. They just work. Chromatography, more often than not, does no.
Sure, we could argue that developing new AI models for whatever use case will require more education than a 20-hour React course. Yet the option to make that app on your PJs is still there.
Just as great tennis players love hitting tennis balls. What ‘balls’ do biotechnologists love to hit?