Spotlight on Adrian Horgan, Director of Advanced Research
Spotlight is a series of interviews with DNA Script's employees. Twice a month, learn more about our proud team members. What do they do every day? What challenges do they encounter? What are their perspectives?
This week, we talk to Adrian Horgan, Director of Advanced Research in Paris.
What is your background? What did you do before joining DNA Script?
I obtained my Ph.D. in Polymer and Colloid Chemistry from the University of Bristol in 2000. My research was funded by ICI and involved the synthesis of block and graft copolymers and their use as steric stabilizers to make dispersions of small nanoparticles (10 nanometers), which I characterized with small-angle neutron scattering and other techniques that employ mathematical models and involve fitting structural parameters to data.
All of my peers in the Polymers at Interfaces Group (‘PIGs’) were industrially-funded, and after graduating, many joined companies like Schlumberger, P&G, Unilever, GSK, DuPont, BP, Lubrizol and Pfizer. I wanted to travel abroad and chose instead to pursue postdoctoral research in the department of Chemical Engineering at Columbia University in New York. Its aim was to use polymer and polyelectrolyte theory to explain the hybridization behavior of DNA at surfaces after performing the necessary kinetic and thermodynamic measurements, which involved learning how to immobilize DNA molecules on surfaces and constructing and automating an optical instrument with fluidics. The experience I gained at Columbia helped me find a position at a startup in England called Solexa Ltd., where I helped develop the sequencing-by-synthesis with reversible terminators approach used in Illumina’s next-generation DNA sequencers.
Around the time Solexa became a listed, publicly-traded company, I joined a newly-formed University of Cambridge spin-out hoping to reduce another novel, promising idea to practice and help it move through development and scale-up to market. The development of new, innovative technologies usually requires a broad range of expertise but early-stage startups lacking funds benefit from ‘jack of all trades’ like myself who are willing to try new things and like a challenge. For example, at Smart Holograms, I was compelled to learn holography, which involved spending many hours in a dark room (not for the first time) directing pulsed and continuous lasers at photosensitive materials.
Adrian thrives as a jack-of-all-trades both at work and at home, where he has taken on a small plumbing project.
What is your position and role today?
Before joining DNA Script as a Consultant almost three years ago, I was a Group Leader in Electronics and Modelling and a Group Leader in Biotechnology at the National Physical Laboratory in the U.K as well as a Product Science Leader at AkzoNobel (formerly ICI). By virtue of the groups being large, these roles predominantly involved project and people management. Then in 2013, I moved to France for family reasons and, while trying to settle, assumed various interim positions (e.g., CTO, CEO, Consultant) before joining DNA Script.
Xavier Godron, CTO at DNA Script and one of its three founders, contacted me in October 2017 after a referral by Geoff Smith, a former colleague at Illumina. When I met with Xavier and Thomas Ybert (DNA Script’s CEO), it was clear there was a surface chemistry problem that I could probably help with, but I was uncertain if it would be a quick fix or would require a sustained effort. Either way, it seemed like it would be easier to resolve by experiencing it first hand than by reviewing data across a table in a meeting, so I offered to go into the lab. While I was very impressed by Xavier and Thomas and their vision, my preference was for a short-term consultancy contract because I am problem-focused and didn’t feel ready to jump into another startup with both feet.
As a Consultant at DNA Script I did the early proof of concept work for SYNTAX?, which will be DNA Script's first product and the world’s first DNA printer powered by enzymes. Today, I lead Advanced Research, which, as the name suggests, is working on future ways to do DNA synthesis, in particular, testing approaches to reduce the scale of enzymatic DNA synthesis by employing technologies able to localize, confine or activate minute quantities of DNA precursors at planar or spherical solid supports made of materials for genomics applications.
3. What does a standard workday entail?
My day begins when I board the train at 07:40. I live in the countryside outside Paris, and my commute is an opportunity to send emails, read articles and patents and plan my day. On arriving at Kremlin-Bicêtre, I usually head straight for the kitchen and help myself to a large cup of black coffee. I then catch up with members of the team, and we discuss priorities, promising results and difficulties. DNA Script is lucky to have so many dedicated and competent people, and the people in my team count among them. We have different native tongues, but two things we share in common are a physical-sciences background and a fondness for technology. A typical day for us might involve planning and doing experiments, analyzing data, ordering components and reagents, writing a technical report or presentation and attending an internal or external project meeting. A few tasks are repetitive and mundane, but lots of what we do has not been done before — and it’s always exciting when something works for the first time, or we glean some new insight.
What are future challenges that you anticipate for your position? How would you like to grow?
Having worked at the U.K.’s national measurement institute when it was run for profit on a GOCO model by Serco Plc., I’m aware of Lord Kelvin’s quote, “if you cannot measure it, you cannot improve it.” One of the challenges we face when synthesizing small quantities of DNA in many positions simultaneously is obtaining the requisite control and monitoring any aberrant microscale process behavior. As we reduce the scale of synthesis and aim for larger and larger sequence diversity for applications such as DNA data storage, it becomes harder to know reaction yield and determine whether the sequences in each position contain missing, additional or incorrect bases. Many of the analytical methods available are simply not sensitive enough or require rounds of amplification with the possibility of introducing bias. As a result, we spend a lot of time at DNA Script thinking of better ways to measure parameters of interest. It helps explains why DNA Script has made unparalleled improvements in length and purity and leads the field in enzymatic DNA synthesis.
While I’m thrilled to see the SYNTAX? DNA printer take-off, the thing I’m most excited about at the moment is our collaboration with Harvard University and the Broad Institute of MIT and Harvard. Together we are developing a more sustainable way to meet the very significant future demands for data storage capacity (375 exabytes by 2040 *). Our approach will harness the superior storage density (petabytes per gram – 1000 times) and durability (up to millions of years) of DNA compared to magnetic tape and today’s compact solid-state storage media and will involve enzymatically synthesizing in a high-throughput manner the 1s and 0s that make up electronic files as DNA sequences on a silicon chip. Once the information is stored in the form of As, Cs, Gs, and Ts, each sequence can be read and converted back into 1s and 0s of the original file by DNA sequencing, which continues to become faster, more accurate and cheaper. I’m keen to help the consortium achieve its aims over the next four years and hope to meet again our Harvard and Broad partners as well as members of the body funding the work (IARPA) in person when travel restrictions due to Covid-19 are lifted. For the interested reader, vaccine development and PCR testing are also areas where DNA Script’s technology has a potentially important role to play: https://dnascript.com/testing-challenges-with-covid-19-why-dna-synthesis-is-critical/
* DNA assembly for nanopore data storage readout, https://doi.org/10.1038/s41467-019-10978-4