Why it’s time for another genomics grand challenge

By Andrew Hessel, distinguished researcher, Autodesk

“Make no little plans … ” — Daniel Burnham

For the past five years, an international team of scientists has been working to synthesize the largest genome yet — the yeast genome. It consists of about 12 million base pairs organized into 16 chromosomes that are structurally similar to those of humans. While still under construction, the project is moving ahead well and with the end in sight, scientists are already thinking about what they should build next. The fruit fly genome? The worm?

On stage last summer at the synthetic yeast summit in New York, the panel moderator, Nancy Kelley, a key figure in the city’s life science institutions, asked what I thought this next synthetic step should be. My answer took the audience, mostly scientists, by surprise.

I said that we had to write the human genome.

Such a project would generate a wealth of information that connects DNA code to function. It would improve our understanding of how cellular systems — the foundation of the natural world — actually work. The practical applications could be enormous. Writing the human genome could make personalized medicine more affordable and accessible. It could also lead to 3D-printed organs for transplantation, virus- and aging-resistant cell lines, and synthetic vaccines made on demand. Plus, it could stimulate everything from synthetic biology education, to regulatory reforms, to IP management in DNA technologies — and probably a lot more.

More than a decade ago, scientists successfully closed the book on the human genome project (HGP-read), completing the sequencing (or “reading”) of the 3 billion base pairs of DNA code that make up our genetic blueprint.

When it was first proposed, HGP-read was a crazy idea. DNA sequencing was brand new. Reading just a few hundred bases of genetic code was hard, slow work. To consider reading billions was preposterous. And the money involved — an estimated $1 per base — put the project squarely in moonshot territory, an unfamiliar place for biological scientists.

Despite criticism and skepticism, HGP-read was a resounding success, declared complete a full two years early and under budget. Since then, sequencing technology has continued to advance and is widely used in research, as well as human and animal health. In retrospect, the early proponents of HGP-read weren’t nuts. They were visionaries and pioneers.

HGP-read was — and remains — the biggest collaborative project ever done in life science.

For the last 12 years, I’ve worked personally and professionally to evangelize and advance synthetic biology. I believe it’s the most important technology humanity has ever developed, and it’s a dream come true to be a part of its evolution.

These days, I work with Autodesk, a company that makes sophisticated design and engineering software that is used for building much of the world around us. For the last few years, Autodesk’s Bio/Nano Research group has been exploring and developing tools for designing the unseen world of molecular and cellular systems.

Writing the human genome could make personalized medicine more affordable and accessible. It could also lead to 3D-printed organs for transplantation, virus- and aging-resistant cell lines, and synthetic vaccines made on demand.

But unfortunately, synthetic biology has a massive PR problem. The field is more than 15 years old and moving incredibly fast. It’s opening a door to making designer organisms. This is incredibly important and will eventually touch on everything from health, to manufacturing, to national security. The only thing that even comes close to synthetic biology’s potential to shape our future is computers. And they are toys compared to living systems.

Yet outside of a relatively compact R&D community, most people haven’t even heard the term synthetic biology. Even fewer have any clue about its true power and potential. The science and the emerging industry, already worth tens of billions of dollars, is virtually invisible, completely off the radar.

The field is waiting to be discovered. And what it needs is a breakout moment, something that will get it noticed, something that will get people interested enough to care.

It needs a grand challenge.

Let me be clear: synthesizing any genome is a challenge. But to be grand … well, it has to do something related to humanity. Otherwise it’s just not going to be universally relevant to all people.

The founders of HGP-read knew this. They had to dig in and commit to it. If they had played it safe, they would have proposed sequencing a mouse or a monkey.

I believe that synthetic biologists need to embrace this spirit, too, and there isn’t a moment to waste. The window of opportunity is running out.

Current estimates put the cost of writing a human genome at $100M. A lot of money, but not outside the range that companies will invest in, or that philanthropists will write a check for. Which means the synthesis of the human genome is already up for grabs to at least a few groups and the list will just keep growing. If the technology keeps advancing at the current rate, by 2025 writing a human genome could cost less than $10M.

This will be the second human genome project, standing on the breakthroughs of the first and completing the foundational toolkit.

I strongly believe that academic scientists should lead this work. So, after the summit in New York, I called Harvard geneticist George Church, who was involved with HGP-read at the very start and is a world leader in synthetic biology. He agreed that the idea should be considered more and was open to leading an investigation, with one condition: the architect of the synthetic yeast project, NYU’s Jef Boeke, would have to agree to co-lead.

I was worried that I had scared Dr. Boeke a bit with my comments in New York but Nancy Kelley worked on sealing that deal while I went to speak with my bosses.

Autodesk CTO Jeff Kowalski was very interested but cautious. We were both pleasantly surprised with how quickly our CEO, Carl Bass, voiced support for Autodesk involvement and committed sponsorship funds to bring key scientists and other stakeholders together for deeper discussion.

As a result of all this, today in Science we joined a group of prominent science and policy leaders in announcing our intention to launch the Genome Project-write, or HGP-write, later this year.

This will be the second human genome project, standing on the breakthroughs of the first and completing the foundational toolkit. Like HGP-read, this will be an open, international research project led by a multi-disciplinary group of scientists. The central goal is to reduce the cost of engineering and testing large genomes, including a human genome, in a cell line within ten years. (Sorry to disappoint but no synthetic humans will be produced here.)

Really, it would be hard to overstate the potential impact of this project on human health and our understanding of the natural world. Physicist Richard Feynman wrote, “What I cannot create, I do not understand.” If HGP-write can reach its 10-year goals, our capability to design and create living systems will be far greater than it is today.

Yet the most valuable thing to come from the launch of HGP-write may simply be inspiration. Grand challenges push us to work together, to solve big problems, and to grow as a species. HGP-read was certainly all this and more for me and millions of others. It’s fair to say it shaped my life — and changed the world.

The clock is ticking. The next 10 years are going to go by very fast.

Andrew Hessel is a futurist and catalyst in biological technologies, helping industry, academics and authorities better understand the changes happening in life science. He is a Distinguished Researcher with Autodesk in its Bio/Nano Research Group, based out of San Francisco.