Digitising biology: what is life now?

In February 1943, the then head of the Irish government Éamon de Valera and more than 400 others filled the public theatre in Trinity College, Dublin, to hear the Nobel Prize-winning physicist Erwin Schrödinger deliver the series of lectures entitled ‘What is Life?’ The three lectures formed the basis for his book of the same name which was published in 1944 and which has influenced the great and good of molecular science ever since.

Again under the auspices of the Dublin Institute for Advanced Studies (DIAS), where Schrödinger was Director of the School of Theoretical Physics for 17 years, this week saw people turned away from the doors of the same public theatre on the occasion of a modern update to the original lectures.

Taking the stage alongside the current Director of the School of Theoretical Physics, Professor Luke Drury, and Professor of Biochemistry at Trinity College, Professor Luke O’Neill, was Dr J Craig Venter, one of the most feted figures in contemporary biology. As well as being the first human to have their personal genome sequenced, Dr Venter headed the team which created the first cell with a fully synthetic genome and is founder and director of the J Craig Venter Institute (JCVI), a not-for-profit centre for genomics research in the United States.

The event was organised as part of the Euroscience Open Forum (ESOF) 2012. Dr Venter began by saying that the aim of his talk was to convince the audience - which included the present Taoiseach, Enda Kenny, and representatives of the European Commission - that substantial progress has been made on the question in the last 70 years.

After giving a brief timeline of developments in molecular genetics since 1944, when Avery, MacLeod and McCarty demonstrated that it was DNA which causes bacterial transformation. Dr Venter described how strong bias against DNA and for proteins as carriers of genetic material meant that the impact of this discovery – as was also the case for the subsequent discovery of the double helix structure – was far from instantaneous.

Dr Venter went on to elaborate on the rapidly diminishing distinction between biological code and digital code, making the argument that ‘everything can be reduced to ones and zeros’. The genetic ‘code-script’ was first termed such by Schrödinger on the same stage almost 70 years ago, when he also likened this hypothesised code-script to Morse codes binary system of dots and dashes, a comparison that Venter has drawn on.

"I describe DNA as the software and when we activate a synthetic genome in a cell we describe it as ‘booting up’, the same way you would boot up software on a computer. June 23^rd this year would’ve been Alan Turing’s hundredth birthday. His Turing machines described a set of instructions on a tape. He also described a universal Turing machine, which could take those instructions and rewrite them – the origin of the digital computer."

Dr Venter echoed analogies comparing life to Turing and Von Neumann machines, with cells as biological machines containing a self-replicating code based on an internal description of itself. According to his extension of this metaphor, DNA is the software of life and proteins are the hardware of life: nature’s robots.

"There is a unique protein for every single task in the cell," he reiterated. "These proteins act based on their structure alone, without consciousness or the control of a higher mind or centre. Everything a protein does is built into its linear code, which is derived from the DNA code."

The most important breakthrough besides the genetic code, Dr Venter argued, is the determination of the process of protein synthesis. Without this complex, ceaseless process, life could not exist.

"We all shed around five million skin cells per day, and around 5 x 10¹¹ of our blood cells die every day," he pointed out. "During normal organ development, 50 per cent of cells die. Life is a dynamic process of decay and self-renewal."

Transcription and translation are the key processes in the perpetuation and self-replication of cells, and Dr Venter remarked that if they worked more efficiently and with fewer errors we would face far fewer health problems. Protein misfolding, for example, accounts for many common chronic diseases such as Alzheimer’s and BSE, or mad cow disease. Progress has already been made in developing treatments for cystic fibrosis, which is often caused by a single mutation.

"The machines that make DNA are not very accurate," he said. "The longer the piece of DNA, the more errors can occur, so we need to find ways to prevent these errors."

The need to avoid this type of error was just one of the challenges faced by Dr Venter and his colleagues in the complex process of synthesising a genome and inserting it into a host cell, of which he gave an account during the lecture.

At a press conference prior to the event, Dr Venter fielded questions on the ethics and accountability of the research carried out at JCVI and other institutes. He commented that the science community is probably the best sub-community in the world in terms of subscribing to and upholding a code of ethical standards, particularly given the fact that relatively few regulations are in place. Many have expressed concerns about the risks of releasing synthetic organisms into the environment. The watermarking of genetic code was a topic he also discussed in his lecture.

"We watermark DNA so that it is always possible to tell a synthetic species apart from a naturally-occurring one," Dr Venter explained. "We started by inserting a single amino acid marker, but were accused of a lack of imagination."

The criticism spurred the team on to insert coded lines of text – including quotes from James Joyce and Richard Feynman – into the genome of the bacteria Mycoplasma mycoides. They even included a URL in one genome, creating the first organism to have its own web address encoded in its DNA.

Dr Venter looked forward to a future in which the digitisation of biology will mean that vaccines can be distributed via email, with downloadable access available to every individual within hours or even minutes of an outbreak of influenza, for example. There are also hopes that synthetic biology will be able to address other pressing global problems such as hunger and climate change.

James D Watson, who shared the Nobel Prize for Medicine in 1962 for his role in the discovery of the structure of DNA, was also in the audience and congratulated Dr Venter after his talk. Both Watson and Francis Crick cited Schrödinger’s influence on their work; work which paved the way for the discoveries and developments Venter outlined, illustrating just how far our understanding of what life is has come in the last 70 years.