Synthetic Life: Craig Venter

Synthetic DNA, digital code and genome transplantation were among the exciting topics at the most brilliant lecture I have ever attended. 69 years after Erwin Schrödinger’s original ‘What is Life?‘ lecture, Dr. Craig Venter was asked to speak on ‘What is Life? A 21st Century Perspective‘. Taking place in the same venue as the original event, I knew this would be special but I was completely blown away. In 1943, the lecture took place on a cold winter’s night. Here’s what happened in Trinity’s Exam Hall on a rainy summer evening!

“The digital and biological worlds are now becoming interchangeable” – Craig Venter

Dr. Craig Venter with An Taoiseach Enda Kenny TD
Image: Maxwell’s Dublin (& top photo)

The lecture was kicked off by Prof. Luke Drury with a background of how public lectures were instilled in Irish Institutions. When setting up specialised research groups such as the Dublin Institute for Advanced Studies, Éamon de Valera asked his old teacher (and Royal Astronomer of Ireland) Edmund Taylor Whittaker for guidance. He advised that the hardest thing to do was a public lecture. In the 1930s de Valera wrote into law that each institute much give an annual public lecture. There were many remarks about that era of Irish history… one of which involved the Provost of Trinity getting regular calls from Áras an Uachtaráin as the President had queries of a mathematical nature!

With the context of public lectures set, Prof. Luke O’ Neill described the importance of Erwin Schrödinger’s original lecture. A physicist asking a question fundamental to biology: ‘What is Life?’. He considered the physical nature of the gene and proposed it to be an ‘aperiodic crystal’. It was also the first time ‘genetic code’ was coined. Many scientists were inspired to study genetics after reading the book published following this lecture series. An audience member was among these… James Watson (pictured below).

Image: Maxwell’s Dublin

Venter began with the substantial progress in the last nearly 70 years since Schrödinger’s lecture. As a non-practicing geneticist, I was thrilled to hear Venter speak about the race to sequence the first human genome. He started a race with the National Institutes of Health (NIH), 8 years after they had begun The Human Genome Project. Using the new shotgun technique both his company and the NIH published the fully sequenced genome at the same time in 2000. An unbelieveable achievement for Venter and the shotgun method is now almost exclusively used for genome sequencing. Speaking of progress… this snippet says it all:

“Instead of years or decades, it now takes about 2 hours to sequence a genome” – Venter

Turning to his most recent research, Venter described making synthetic DNA from digital code. He repeatedly mentioned DNA being the software of life. He challenged his team recently by asking “Could we design and construct a minimal genome of a cell?… Can we boot it up in the cell?” To test this theory, he began with a virus, ΦX174, chosen because very few changes can be made in the genetic code without getting errors. It also has historical relevance as it was the first DNA-based virus to be sequenced. Venter needed to create the DNA of the virus in the lab with no natural virus DNA present to act as a template. He created this piece of completely synthetic DNA and injected it into E. coli. ΦX174 is a bacteriophage (my favourite virus… you may recall) so it initiates a parasite-style alien invasion. The synthetic ΦX174 DNA recruits the E. coli machinery to make new viruses. Venter described this brilliantly as the “software building its own hardware”.

A rough illustration of genome transplantation

Moving on to the next challenge, Venter spoke about genome transplantation. This is essentially converting one species into another! To do this the group had to develop a technique to grow synthetic DNA 1.1 million base pairs long. This was a feat which took a number of years to perfect. Once the synthetic bacterial chromosome was developed, more problems prevented transplantation. Restriction enzymes are present in bacterial cells to protect against invading DNA. The initial problem with genome transplantation was that the host cell’s restriction enzymes recognised the new DNA as foreign and chopped it up. Removing these enzymes enabled the synthetic DNA from one bacteria species to be inserted into a completely different species (see rough drawing on right… similar to Venter’s illustration). “Every protein in the cell came from the new DNA that we had transplanted into the cell”… successfully achieved in 2010!

Speaking of the future, the digital and biological worlds being interchangeable was the common theme. “It is now standard in the world of science to convert digital code into proteins, viruses…”. He spoke of the connectivity of labs around the world and how digital code can be transferred via email and synthesised into biological code. This connectivity will be critical during a time of crisis. Venter mentioned that in the face of a pandemic, we can digitally send a vaccine in seconds around the world!

The talk ended leaving us contemplating the “new frontier of synthetic life”. This cutting edge research requires much reflection as it has implications for both the future of science and ethics. It has left me with so many questions, one of which is ‘What is Life?‘. Perhaps the next lecture will answer that!