A love letter to DNA

DNA has been the foundation of my life. I want to celebrate the molecule on its big day, April 25, with some recollections.

I remember (perhaps wrongly in some cases, memory being what it is) some of these highlights:

• Articles in the news about the first experiments with recombinant DNA. I wasn’t even a teenager yet but I was totally captivated.
• The day in high school that I decided that understanding the cell and its code would be my core passion. This changed the entire course of my education and career. Before this moment, I was mainly interested in cars and computers.
• Spending a whole year organizing every known gene and base pair of the Salmonella typhimurium genome. Mary Cheng and I photocopied thousands of papers.

The hybrid genetic-physical map of Salmonella

• Meeting with Norm Dovichi in early 1995 in Edmonton, Alberta, to pitch a new DNA “sequencing by synthesis” methodology, and him showing me his 32-channel prototype of a capillary electrophoresis sequencing device. Later, I did some calculations and realized that reading the complete genome of a bacteria would soon be trivial. Commercialized, Norm’s work would become the guts of the ABI PRISM 3700, the sequencer that did the heavy lifting in the Human Genome Project.

The ABI 3700 PRISM automated sequencer (image: National Museum of American History)

• The 1995 American Society for Microbiology meeting where J. Craig Venter and Hamilton Smith announced the complete genomes of Mycoplasma and Hemophilus. The energy in the room was incredible! Better than a rock concert.
• Joining the Amgen Institute later that year to put my bioinformatics expertise to work. Not only was the science world-class there but I had an insider’s view of how powerful programming with DNA could be for medicine and humanity. And how profitable the biotech industry could be. Cells turned sugars into gold. I joked at the time that if we bought paper and ink and printing presses and printed cash, our gross margin would decrease.
• Working with Amgen and Celera genomics as the effort to sequence the human genome ramped up. Seeing 300 ABI 3700 PRISM devices in a single room was impressive. So was Celera’s “Mission Control”-style data center.
• Bill Clinton calling the race to sequence the human genome (which had gotten pretty heated between the public and private efforts) a tie, with all humanity the winner. A brilliant piece of politicking, IMO.
• In 2003, shifting my interests from reading and analyzing DNA to writing it. The field of synthetic biology was just getting started. I hosted a synthetic biology meeting in Oklahoma in the fall, bringing Drew Endy, Rob Carlson, and Franco Cerrina to speak at the newly-opened genome center.
• Meeting Stephen Davies in Toronto in 2005. He was organizing Toronto’s iGEM team. The competition was pretty small back then.

2005 iGEM Teams gather at the Stata Center, MIT

• Becoming one of the first iGEM ambassadors in 2006. This was a wild time. The program had almost no resources. It operated out of Tom Knight’s lab at MIT. I slept on a futon and brushed my teeth in a public washroom, sometimes standing beside a barefoot Richard Stallman.
• Meeting Chris Dambrowitz and joining Alberta Ingenuity, an organization advancing science and engineering in Canada. We planted seeds of synthetic biology across the province and country that continue to grow to this day. The iGEM 2007 team focused on making butanol and got national TV coverage on Discovery Channel.
• Attending the SB4.0 meeting in Hong Kong in 2008. The iPhone had come out just the year before. The App Store was starting to explode. I realized one day there would be an App Store for biological code too.
• Writing a draft of the life science program for Singularity University in early 2009, then joining the faculty later that year. The draft focused on digital biology — reading, analyzing, and writing DNA code using software tools, DNA synthesis, and automation. SU operated out of NASA Ames Research Center. It was ground zero for the alpha geeks of Silicon Valley and the early lean years were totally amazing. I got to share stories about synthetic biology for several years both at Ames and abroad.
• Joining Autodesk in 2012 as a Distinguished Researcher. Carlos Olguin, a true visionary, had convinced the company to create a Bio-Nano Programmable Matter group. Just before I started my role, I penned a short article about starting a new human genome project, this time focused on writing our genome. The company championed 3D printing so I started to explore how to 3D print a virus.

Synthetic phage growing on E. coli (Photo: Paul Jashke)

• In 2015, becoming an AAAS-Lemelson ambassador, charged with celebrating invention. My daughter, Rosalind, had just been born. I was nominated by the incredible mycologist Paul Stamets. Right after orientation, I attended the 4th Sc2.0 meeting at the New York Genome Center, where the latest work to synthesize and assemble the yeast genome was being presented. Inspired, I asked George Church to take the lead on the Genome Project-write. He accepted. Meanwhile, Nancy Kelley recruited Jef Boeke.
• My son, Darwin, being born in late 2017. Like his sister, he was made in an IVF lab, but he was comprehensively profiled genetically pre-implantation.
• In 2018, after departing Autodesk, starting Humane Genomics, with the goal of engineering synthetic oncolytic viruses to treat canine cancers, opening the door to bespoke human cancer therapies. Chad Moles and Peter Weijmarshausen rounded out the core team and have taken the company further than I ever could. Today, I am an advisor to the company and a big advocate of programmable medicines.
• Spending much of late 2020 and 2021 writing The Genesis Machine with futurist extraordinaire Amy Webb. The book came out in February 2022 and has been sparking conversations ever since.

There are so many more events and people along this journey that I’m overlooking. Overall, it’s been decades of learning and growing and connecting but DNA technologies are still very much in their infancy. So where are my interests focused today? As always, I’m looking at what’s just ahead. The past we cannot change but we all get to shape the future.

Because of molecular electronics and enzymatic DNA synthesis, I think we’re finally on the cusp of the 1000-fold reduction in assembled DNA we need to really accelerate biological engineering. My hope? That I’ll be able to print and “boot” a synthetic E. coli for about the same price as ordering a sample from ATCC. When we can achieve this milestone, we’ll be on track to start synthesizing more complex genomes, including our own.

I’ve also been championing biobanking as something that should be democratized. Each person is unique but we don’t archive their programs. Sequencing DNA, even whole genome sequencing, isn’t sufficient. We need to bank our cells or at the very least functional nuclei. Think of it as a biological safe deposit box for a really personal keepsake.

And so much more. But I’ll save some of these ideas for another post. Have a great (DNA) day!

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.