The DNA Writing XPRIZE experience
Introduction
This year, kind of by accident, I championed an XPRIZE for DNA Writing.
I’m a proponent of synthetic genomics and XPRIZE is an organization that challenges teams to develop breakthrough technologies to solve grand challenges. It was founded by Dr. Peter Diamandis in 1996.
The first XPRIZE, known as the Ansari XPRIZE for Suborbital Spaceflight, was awarded in 2004 to the SpaceShipOne team for being the first non-governmental organization to launch a reusable manned spacecraft into space twice within two weeks. The achievement received global attention and helped launch the commercial space industry.
Since then, XPRIZE has become a platform, with impressive results. (Get their recent Impact Report here.)
Peter Diamandis put out a call for new prize ideas earlier this year. I used to see Peter regularly in the early days of Singularity University, but I hadn’t seen him in a long time. I pinged him asking if Dr. George Church had spoken to him about a DNA synthesis XPRIZE. We’d discussed it on a Genome Project-write board call. He suggested I contact Dr. Daniel Kraft who was heading up the Health domain. I did and suddenly found myself in the XPRIZE Brain Trust.
After long chats with GPT-4, several months of online meetings, and two intense and incredible days of in-person prize development and elimination rounds with the Brain Trust folks, the DNA Writing XPRIZE made it into the finals. I presented it to a voting audience of invited guests, including investors at the 2023 Visioneering Conclave.
I’ve shared the pitch here, edited for readability and to flesh out key points.
Can you imagine a world where a single technology enables medicines on demand, food abundance, unlimited energy, biodiversity preservation, and precision manufacturing?
All of this and more can be achieved by writing DNA to harness the incredible power of biology.
All life is based on cells. All cells have DNA-based programs that determine how they are constructed and operate — basically, their operating system.
Reading DNA informs us.
It allows us to directly read the code of life. It’s the most powerful diagnostic technology we have, allowing us to see proteins, determine what’s broken in a cancer cell, and what microorganisms are present in a sample of seawater. It even allows us to go back in time to determine how we evolved, work that won a Nobel prize in 2022.
Writing DNA empowers us.
It allows us to engineer biology and create a nearly infinite array of products — everything from medicines and vaccines to new materials and foods. It makes programming a living cell similar to programming a computer.
Put simply, anything that biology can make, writing DNA allows us to make, too.
This makes DNA writing more powerful than reading DNA by a long shot.
Reading is Cheap, Writing is Expensive
Unfortunately, there’s a huge economic gulf between our ability to read and write DNA.
Today, just one dollar will allow over 350 million bases of DNA to be read but just 15 bases of DNA to be written.
Writing DNA is more than 20 million times more expensive than reading DNA.
This is a gigantic brake on biological innovation.
Why such a massive gap? Two reasons.
One is the $3 billion dollar Human Genome Project — the biggest life science project ever. This kickstarted scientists around the world to work on sequencing tools and techniques.
Another is that after the human genome was successfully completed in 2003, groups didn’t stop developing new DNA sequencing technologies. As so-called “Next-generation Sequencing” (NGS) systems were commercialized, they dramatically reduced sequencing costs year over year.
The result? DNA sequencing outpaced even Moore’s Law (the falling price of transistors) by as much as 500%. This is why a human genome can be sequenced today for as little as $100.
Without this support and attention, DNA writing has lagged behind, despite it being so fundamental to genetic engineering. The costs still dropped — in 2000, it cost about $20 to write a base while today it’s as little as $0.07 — but this decrease was merely exponential, not super-exponential.
If we want to harness the power of biology to solve humanity’s biggest challenges, better DNA writing technology is the place to start.
The DNA Writing XPRIZE will incentivize the development of next-generation DNA writing technologies that are faster, cheaper, and able to write longer chains of DNA.
Why is this important?
Cheaper DNA writing will fuel more experiments in life science, even those that are high-risk and likely to fail but promise breakthroughs if successful.
Faster DNA writing means more iterations during development, accelerating progress.
Writing longer DNA facilitates the study and engineering of larger genes, whole pathways, and even entire genomes. It allows for more ambitious projects such as the creation of novel organisms or the redesign of existing organisms with enhanced or entirely new functions.
Overall, next-generation DNA writing will take bioengineering to the next level, creating a tide that can raise all ships.
From Rocket Ships to Rocket Chips
But wait! There are already many companies that specialize in writing DNA. Why isn’t the market making these next-generation writing technologies? Why do we need a moonshot like XPRIZE?
The answer here is a bit complicated.
Customers that buy DNA today are a diverse group consisting of a few thousand individual scientists and companies scattered around the globe. The majority are small labs with limited budgets. Because DNA is still relatively expensive — about $200 for a gene-sized construct — most customers typically work with single genes or proteins. If they need longer DNA, they assemble it themselves to save money. Very few customers design or build complete genomes because it would be prohibitively expensive. Instead, they edit them with CRISPR-Cas or similar systems.
Companies that write and ship DNA to customers are relatively few. Here, technology development has mainly been to reduce cost and shorten turnaround times for gene-sized DNA, a few thousand bases. In recent years, there has been a shift away from chemical DNA synthesis toward enzymatic DNA writing, which has simplified the reagents, made them less toxic, and allowed for slightly longer DNA strands to be written — up to 1000 bases. But nothing truly breakthrough like cheap microbial genome-scale DNA writing is imminent.
Overall, DNA writing is stuck performance-wise at less than 10,000 very expensive bases, for relatively few customers.
But we could be on the cusp of a technological breakthrough. Early in 2022, a paper in the prestigious Proceedings of the National Academy of Sciences (PNAS) described the development and capabilities of the world’s first commercial Molecular Electronic chip. This device is something of a game-changer. Costing about $60 million to develop, it represents the successful marriage of biomolecules like DNA, RNA, and proteins directly to semiconductor chips like those in our computers and phones.
The new chip was shown to be able to sequence DNA by electronically recording the activity of DNA writing enzymes. Further development of these or similar chips could permit direct electronic or optical control of these enzymes, opening the door to chip-based DNA printers.
Nudging engineers in semiconductor development to work with biomolecular engineers could see novel molecular electronic chipsets developed for DNA writing that are orders of magnitude better than anything available today and more.
And bringing people together to produce breakthroughs is what XPRIZE does best.
Scoping the Prize
One thing I’ve always loved about the first XPRIZE was how easy it was to describe:
Build a ship to go to space twice in two weeks.
Even a child can appreciate this and the metrics are crystal clear.
My yardstick is the venerable E. coli bacterium. It’s the best-recognized bacterium by the general public and the most-understood single-celled organism in life science. It was completely sequenced in 1997 and the full metabolic wiring diagram is known. It’s widely used in research and development. Most importantly, in ideal growth conditions, it can flawlessly copy its ~5 million basepair genome in just 20 minutes.
The clear and measurable goal for XPRIZE teams? Try to match the bug’s DNA writing performance.
Put another way:
String together 5 million bases of DNA as quickly as possible.
The total prize purse? A cool $100 million dollars.
Testing and judging is about as simple as it gets. When a team believes they have reached the 5 million base threshold, they are sent a computer-generated file of digital DNA code. This DNA is randomly generated and does not code anything biological in particular. Produced on demand, it cannot be known in advance by a team.
Once the team receives the file, the clock is started. When the molecular DNA code is received, the clock is stopped.
Judging is then done by an independent group to evaluate the DNA size and sequence using standard technologies. Also scrutinized will be costs related to production.
The goal is for multiple teams to reach the 5 million base threshold and to compete mainly on accuracy, turnaround time, and cost. And perhaps device size and even aesthetics. Chip-based, DNA writers could look similar to a phone or even be included in future phones.
Impact
Successful completion of the DNA Writing XPRIZE will have world-changing impacts.
For one, it will deliver breakthrough new DNA writing technologies that may fit in your pocket. Need a vaccine? Just print it. Your body will be the manufacturing plant.
But there’s so much more. Reaching 5M base synthesis capacity will open the floodgates to microbial engineering. It will allow the entire genetic program for a microbe to be made from scratch, probably at a very low cost. It will make programming simple cells possible.
Follow-on chip development will permit the boot-up and testing of these organisms on-chip as well. A new molecular electronic “biochip” industry will blossom.
It will also potentially save millions of lives by making the manufacturing of medicines like cancer therapies and vaccines as simple as downloading a file. And not just old medicines —the latest and greatest state-of-the-art personalized ones. It will ultimately lead to a revolution in the pharmaceutical industry.
These newfound capabilities will launch a new digital era for bioengineering, increasing innovation and competition across the board. Programming living cells will come into reach of millions more developers. The biggest (and perhaps only) comparable is when computers when from mainframes to PCs.
This will grow and accelerate the global bioeconomy, already estimated to be more than 5% of GDP here in the USA. Multiple trillion-dollar new industries, from biochips to personalized pharmaceuticals, will emerge.
There’s more. Harnessing biology promises to rid the world of toxic chemicals, pull CO2 from the air as a feedstock, and purify and desalinate water at scale. DNA writing will supercharge the development of these solutions.
In summary, DNA writing will power creating the solutions to humanity’s biggest challenges in health, food production, energy, and protecting our environment.
Questions and Answers
There were Q&A sessions after each presentation. They touched on similar points.
Is this suited for an XPRIZE?
The general agreement here was a resounding “Yes!” as the metrics were clear, the work was audacious and impactful, and it was likely to draw enough participants to join, compete, and ultimately succeed.
One concern raised was that XPRIZE had canceled a DNA Reading XPRIZE. The technology was moving too quickly and didn’t need an incentive.
But DNA Writing is a very different beast. It’s creative and leads to novel inventions and applications that are patentable or licensable. Faster, cheaper, longer DNA writing is a bioeconomic supercharger.
We see the positives. But won’t this empower the dark side, increasing risk?
This was by far the biggest and most commonly held concern.
Some of the smallest things to engineer genome-wise are viruses. These have great utility as vaccines, antibiotics, and delivery systems for gene therapies. But we’re demonstrably vulnerable to some of these agents and have relatively few detection and countermeasures in place, even after Covid.
There’s growing awareness of these biosecurity issues from multiple groups. It’s overdue. The first engineered virus was demonstrated over 20 years ago. Even with current DNA writing technology, they only cost a few thousand dollars to make — a low barrier. And AI tools could make them more potent or accessible to non-experts.
One key solution is to screen all DNA sequences before we print them. Most large synthesis companies are members of the International Gene Synthesis Consortium and do this already. There are other organizations like the Secure DNA Foundation that offer this service for free to anyone. But more work needs to be done.
And, of course, DNA writing is likely our best defense against any new pathogen, including those that nature inevitably generates.
Really, the Current DNA writing technology — again, already capable of producing deadly agents — is widely available today around the globe from an array of providers, some that are not members of the IGSC or otherwise regulated. One desktop DNA synthesizer has already been commercially deployed by a French company and more are in development.
If anything, the increased awareness that a DNA Writing XPRIZE would generate — and XPRIZE’s ability to bring together innovators from around the glove — would speed the development of new guardrails and defense systems, including those incorporated into the chips themselves.
Would would fund this XPRIZE? Who would participate?
Drafts of the DNA Writing XPRIZE presentation and supporting documents shared with US agencies generated and other experts universally positive feedback and expressions of support in both dollars and in-kind services. Several suggested increasing the size of the purse — initially $30 million — given the profound economic potential.
As for participants, the core technologies that need to come together to produce new molecular electronic chips are semiconductor engineers and biomolecular engineers. Both groups have deep talent pools and access to production technologies in their domains but they rarely interact and cross-fertilize. But now that some of the capabilities of molecular electronics have been demonstrated and peer-reviewed, the major intellectual barrier to innovation has been shattered. And XPRIZE is well-positioned to inspire breakthroughs.
Visioneering Results
The DNA Writing XPRIZE didn’t win best of show at the conclave. It came in second out of ten.
Health took home the win, though, with the team led by Dr. Rick Bright, former head of the Biomedical Advanced Research and Development Agency (BARDA), for their MedMaker prize sketch — a medicine printer for anyone, particularly the impoverished. It was a well-deserved win. Their presentation and pitch were top-tier, and Rick is brilliant, charismatic, and articulate. And a natural team leader.
I was way out of my league.
But the creation of an XPRIZE takes one essential ingredient: Money. If seed funding can be raised for prize development by the XPRIZE team — a deep dive into the prize dynamics — it will advance. And if the prize gets backers for the purse and operational overheads, it will launch.
Thoughts about the Future
Humanity needs to be prepared for the arrival of microbial genome-scale synthesis. In the words of one XPRIZE trustee I spoke with, “It will change everything.” It’s appearance is also inevitable.
I expect programming life to follow in the footsteps of programming computers. The more people that gain access to DNA writing technology, the more creative expression will be unleashed, and the more intellectual and commercial success that will happen. This is already happening, evidenced by the rapid growth of training programs like iGEM and the industry hub SynBioBeta.
The rate of innovation could be far higher than with computer systems because the limiting factor to programming cells is how quickly we can write their DNA-based software. The cells do all the heavy lifting of growing and manufacturing the products. No new factories are required.
Like our addiction to more CPU speed, memory, and connectivity, I expect the desire for better, faster, cheaper DNA writing technology will be insatiable. And with each advance in long DNA writing capability, a larger spectrum of the tree of life (based on genome size) will open up for engineering.
The grand challenge for our time is how to land this stunningly powerful technology on a species that is not yet fully prepared for the responsibility it demands.
This is why a DNA Writing XPRIZE matters.
Thanks for reading!
Andrew Hessel is the co-author of The Genesis Machine: Our Quest to Rewrite Life in the Age of Synthetic Biology. He’s also the co-founder of Humane Genomics, a company that makes artificial viruses that target cancer, and the Genome Project-write, a champion of whole-genome engineering. He loves thinking about possible futures through the lens of biology and empathizes with molecules and microbes.
