2009 : WHAT WILL CHANGE EVERYTHING?

In science, as with most areas, seemingly simple ideas can and have changed everything. Just one hundred and fifty years ago Charles Darwin'sOn the Origin of Species was published and immediately impacted science and society by describing the process of evolution as natural selection but nobody understood why or how this process happened. It took until the 1940's to establish that the substance that carried the inheritable information was DNA. In 1953 an Englishman and an American, Crick and Watson, proposed that DNA is formed as a spiraling ladder — or double helix — with the bases A-T and C-G paired (base pairs) to form the rungs, however no one knew what the code of life actually was.

In the 1960's some of the first secrets of our "genetic code" were revealed with the discovery that the chemical bases should be read in groups of three. These "nucleotide triplets" then defined and coded for amino acids.

In the late 1970's the complete genetic code (5,000 nucleotides) of a phage (a small virus that kills E. coli, a type of bacteria) was read out in sequence by a new technology developed by Fred Sanger from Cambridge. This technology named Sanger sequencing would dominate genetics for the next 25 years.

In 1995 my team read the complete genetic code of the chromosome containing all of the genetic information for a bacterium. The genome of the bacteria that we decoded was over 1.8 million nucleotides long and coded for all the proteins associated with the life of the bacteria. Based on our new methods there was an explosion of new data from decoded genomes of many living species including humans.

Just as Darwin observed evolution in the changes that he saw in various species of finches, land and sea iguanas, and tortoises, the genomics community is now studying the changes in the genetic code that are associated with human traits and disease and the differences among us by reading the genetic code of many humans and comparing them. The technology is changing rapidly where soon it will be common place for everyone to know their own genetic code. This will change the practice of medicine from treating disease after it happens to preventing disease before its onset. Understanding the mutations and variations in the genetic code will clearly help us to understand our own evolution.

Science is changing dramatically again as we use all our new tools to understand life and perhaps even to redesign it. The genetic code is the result of over 3.5 billion years of evolution and is common to all life on our planet. We have been reading the genetic code for a few decades and are gaining in how it programs for life.

In a series of experiments to better understand the genetic code, my colleagues and I developed new ways to chemically synthesize DNA in the laboratory. First we synthesized the genetic code of the same virus that Sanger and colleagues decoded in 1977. When this large synthetic molecule was inserted into a bacterium, the cellular machinery in the bacteria was not only able to read the synthetic genetic code, but the cell was also able to produce the proteins coded for by the DNA. The proteins self assembled to produce the virus particle that was then able to infect other bacteria. Over the past few years we were able to chemically make an entire bacterial chromosome, which at more than 582,000 nucleotides is the largest man-made chemical produced to date.

We have now shown that DNA is absolutely the information-coded material of life by completely transforming one species into another simply by changing the DNA in the cell. By inserting a new chromosome into a cell and eliminating the existing chromosome all the characteristics of the original species were lost and replaced by what was coded for on the new chromosome. Very soon we will be able to do the same experiment with the synthetic chromosome.

We can start with digitized genetic information and four bottles of chemicals and write new software of life to direct organisms to do processes that are desperately needed, like create renewable biofuels and recycle carbon dioxide. As we learn from 3.5 billion years of evolution we will convert billions of years into decades and change not only conceptually how we view life but life itself.