At the Cosmos Club, Washington, DC
November 17, 2017
President Larry Millstein called the 2,383rd meeting of the Society to order at 8:06 p.m. President Millstein announced the order of business, announced the evening’s lecture would be livestreamed on the internet, and welcomed new members. The minutes of the previous meeting were read and approved. President Millstein then introduced the speaker for the evening, Gerald Joyce, Professor at the Salk Institute. His lecture was titled, “Life 2.0: Synthetic Self Replicating and Evolvable Systems.”
Looking at life here on Earth, Dr. Joyce’s research asks where did it come from, how does it work, and can we make another one – in other words, can we make a life 2.0?
Our planet developed 4.5 billion years ago through a process called “orbital gardening,” and was initially a violent, uninhabitable place. Around 4.2 billion years ago, a hydrosphere developed. Pre-biotic chemistry then took place, and many scientists believe around 3.8 billion years ago, the first life came into being. Joyce said this life was based on RNA genetic material, and this RNA life gave birth to the first DNA life around 200 million years later.
Joyce said “we are the dust of the RNA world,” and we can see remnants of that world in our own biology. To wit, our cell ribosomes are RNA machines. They are RNA enzymes that catalyze their own replication, remaking themselves. Many scientists believe than an RNA enzyme was the origin of RNA life on Earth.
RNA molecules are strings of letters, similar to DNA. These strings are molecules that, by virtue of the sequence of the letters, fold into a shape. Some shapes are able to catalyze the self-synthesis of the original RNA string.
To learn about how life began on our planet, Joyce said, we need to either dig up one of these original RNA enzymes, find such an enzyme working in modern life, or make one. RNA deteriorates quickly, so finding an original replicator molecule in the ground is unlikely. And no one has identified such a molecule in living biology. So, he said, he and his team have set out to create an RNA self-replicator in the laboratory.
To create the replicator, Joyce’s team started with short RNA strings, mutated them in the test tube, and selected those that could recreate themselves, carrying out a kind of Darwinian evolution in the test tube. Joyce described the process in considerable detail, showing numerous replicators that act by themselves and some that act in tandem with one another.
Joyce and his team have since spent almost 20 years evolving such molecules to create enzymes that can replicate longer and longer strings of RNA. They also discovered that some of their RNA enzymes can replicate other RNA enzymes even though they are limited in their ability to self-replicate. Joyce also described a variety of approaches to improving and expanding the replicative abilities of these enzymes.
He is also looking forward to exploring how RNA could have led to DNA.
President Millstein then invited questions from the audience.
One member asked Joyce if he believes there was a double-stranded RNA intermediary on the way to DNA. Joyce said it was possible, but it was also possible that there was no intermediate. There are examples of such evolution in known viruses, although he acknowledged viruses are not perfect analogs because they require a host to replicate.
Another member asked where the energy came from to drive the replication. Joyce said the system is not in equilibrium and is being fed by the individual building blocks of the RNA. The chemical reaction of joining building blocks to one another is energetically favorable in the joining direction and actually releases energy, about 10 kcal per mole per bond, driving the reaction forward.
After the question and answer period, President Millstein thanked the speaker, made the usual housekeeping announcements, and invited guests to join the Society. At 9:46 p.m., President Millstein adjourned the 2,383rd meeting of the Society to the social hour.
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