Taking a stride toward synthetic life

Harvard scientists have cleared a key hurdle in the creation of synthetic life, assembling a cell’s critical protein-making machinery in an advance with both practical, industrial applications and that advances the basic understanding of life’s workings.

George Church, a genetics professor at Harvard Medical School and member of Harvard’s Origins of Life Initiative, reported the creation of billions of synthetic ribosomes that readily create a long, complex protein called firefly luciferase.

Church, speaking at a Harvard Alumni Association and Origins of Life Initiative event at the Science Center on Saturday afternoon (March 7), described the advance for the first time publicly as part of an afternoon symposium called “The Future of Life.”

“We have not made artificial life, and that is not our primary goal, but this is a huge milestone in that direction,” Church said in comments on the work before the event.

Ribosomes are bodies inside of each cell that take the instructions from DNA and use them to create the proteins encoded by specific genes. Proteins are critical to forming the body’s structure, including muscles, bones and tendons, and are also critical in its daily functioning, through enzymes, for example, which control metabolism.

“The reason it is a step toward artificial life is that the key component of all living systems is the ribosome, which does protein synthesis. It is the most conserved and one of the most complicated biological machines,” Church said.

Using the bacteria E. coli, Church and Research Fellow Michael Jewett extracted the bacteria’s natural ribosomes, broke them down into their constituent parts, removed the key ribosomal RNA and then synthesized the ribosomal RNA anew from molecules.

Though the advance may create excitement among researchers interested in life’s basic functioning, Church said that the work’s industrial applications were its driving force.

Industry today manufactures proteins on a large scale using natural ribosomes, which evolved over millions of years for natural, not industrial, reasons. Church said that being able to create a ribosome means also being able to tweak it so it better fits industrial needs. One possible use would be to create mirror-image proteins that would be less susceptible to breakdown by enzymes, making them longer-lived.

“You really are in control. It’s like the hood is off and you can tinker directly,” Church said.

The advance breaks a 40-year period with little progress in artificial ribosome creation, Church said. The last significant work in this area was done in 1968, when researchers assembled an artificial ribosome, but in an unusual chemical environment rather than an environment in which protein synthesis normally occurs, as Church and Jewett did.

Church and Jewett expected creating the artificial ribosome and getting it to produce proteins would be the toughest steps in making an artificial cell. They were amazed, Church said, when the task was accomplished in just a year.

The ultimate goal is to create an artificial genome of 151 genes that they believe are the minimum to create a functioning, self-replicating cell. 

“It could be that the hardest steps are still ahead of us,” Church said.

Joining Church at Saturday’s event were human genome pioneer and visiting scholar Craig Venter; Jack Szostak, professor of genetics at Harvard Medical School and Massachusetts General Hospital; George Whitesides, Woodford L. and Ann A. Flowers Professor of Chemistry and Chemical Biology; and Andrew Knoll, Fisher Professor of Natural History and professor of Earth and Planetary Sciences. Harvard Provost Steven E. Hyman introduced the event. It was moderated by professor of astronomy and Origins of Life Director Dimitar Sasselov.

Szostak presented his recent research into the creation and propagation of synthetic cells, showing that membranes form from simple fat molecules spontaneously under certain conditions. In addition to the membranes, he reviewed research into possible ways that basic genetic information may have originally been stored and conveyed in simple RNA-like molecules. His work, he said, is exploring the properties of these RNA-like molecules, seeking variations that make them better early candidates to store and replicate genetic information than either DNA or RNA, which perform those functions in modern cells, but require complex molecular machinery to do so.

In his presentation, Venter described the search for genes around the world, saying that microbes have been found on earth that can withstand radiation levels far beyond that which would be lethal to humans, that can live in corrosive liquids that would eat away a human finger dipped in it, and in a wide array of other environments.  The growing library of genes from creatures of all kinds – totaling 50,000 gene families – has created a database from which industry can pick and choose genes for particular applications. Using genetic engineering, synthetic genomes can be created to do such useful things as create clean-burning synthetic fuels, he said.

“I think we’re limited primarily by our own imagination,” Venter said.