One of biology’s biggest achievements of 2016 was intentionally as small as possible: building a bacterium with only 473 genes. That pint-size genetic blueprint, the smallest for any known free-living cell, is a milestone in a decades-long effort to create an organism containing just the bare essentials necessary to exist and reproduce. Such “minimal genome” cells might eventually serve as templates for lab-made organisms that pump out medicines, make innovative chemicals for industry and agriculture, or churn out other molecules not yet imagined. The project also identified genes crucial for the microbe’s survival yet largely unfamiliar to science, highlighting major gaps in researchers’ grasp of life’s playbook.
The newly engineered bacterium was praised as a technical triumph. In 2010, researchers at the J. Craig Venter Institute in La Jolla, Calif., had stitched together a copy of the entire genome of the bacterium Mycoplasma mycoides and popped it into the cell of another bacterium whose genome had been removed. But that “synthetic cell,” dubbed JCVI-syn1.0, contained a full copy of an existing genome. With more than 1 million chemical building blocks of DNA, including 901 genes, it was far from minimal.
The latest version, JCVI-syn3.0, reported in March in Science (SN: 4/16/16, p. 6), has roughly half that much DNA. It’s also the first cell built using human design principles: One segment of the genome has genes for various processes, such as DNA repair, grouped together rather than scattered willy-nilly. Abandoning the untidiness of evolution for a logic-driven blueprint enables a “plug and play” approach, says Daniel Gibson, a member of the JCVI team. To tinker with a metabolic process such as glycolysis, for example, “Rather than changing one gene, then another, then another, you could pop out a whole module and then pop in a new one.”
Making such fundamental changes to the genome while still getting a functioning cell is noteworthy, says genome scientist George Church of Harvard University. “They could have found that, no matter what they did putting it together, it broke,” Church says.
The potential of synthetic cells is enormous, says Claudia Vickers, a biotechnologist at the Australian Institute for Bioengineering and Nanotechnology in Brisbane. Scientists have succeeded in engineering existing organisms such as yeast to help make, for example, malaria drugs. Now little cellular factories designed to be highly efficient and tailored to specific tasks are within sight, Vickers says.