Researchers for the first time created microbes containing artificial DNA, expanding the universal genetic code that guides life. The advance one day could lead to new antibiotics, vaccines and other medical products not possible with today’s bioscience.
In a report published Wednesday in Nature, the scientists said they created two additions to the normal genetic code, and then prompted bacteria to incorporate these pieces of man-made DNA with few ill effects.
“The cells recognized it as natural,” said chemical biologist Floyd Romesberg at the Scripps Research Institute in La Jolla, Calif., who led the research group.
The experiment demonstrates the feasibility of life-forms based on a different DNA code, independent experts said. Eventually, scientists could use an expanded genetic code to design living cells that could make new medical compounds.
By one recent estimate, the market for biologic and protein-based therapies is expected to reach $165 billion a year by 2018.
“Most people thought this wasn’t possible,” said biochemist Steven Benner at the Foundation for Applied Molecular Evolution in Gainesville, Fla., who wasn’t involved in the project. Many scientists assumed that a normal cell would ignore any imitation DNA. “He has gone inside a cell and gotten it to work and that is a shock,” said Dr. Benner.
As honed by evolution, the genetic instructions for life are written in a simple but powerful code made up of four chemicals: adenine (A), which bonds with thymine (T), and guanine (G), which bonds with cytosine (C), to create two basic building blocks of life called base pairs. Combinations of the base pairs form DNA’s molecular recipes for amino acids and proteins.
With growing mastery, scientists have been tinkering with this natural information-storage system that is found inside every cell. They routinely cut and splice normal DNA to alter plants, bacteria and animals. They have used its ultraminiature storage capacity to encode books, poems and popular music. They even have programmed DNA to perform computer-like calculations.
Hoping to make DNA even more capable, scientists working in a new field called synthetic biology have been trying to perfect alternative genetic codes containing up to 12 DNA characters. Until now, researchers haven’t been able to make the artificial DNA work in a living, reproducing organism.
Several environmental groups have urged that synthetic biology experiments be curtailed until any hazards are better understood.
After a formal review, the U.S. Presidential Commission for the Study of Bioethical Issues concluded in 2010 that there was no need to halt research or impose federal controls.
“You may be changing the language [of DNA] a little, but the implications for changing life as we know it may be limited,” said Harvard Medical School geneticist Raju Kucherlapati, who is a member of the bioethics commission.
In their work, Dr. Romesberg and his team sidestepped a technical problem that had stymied other scientists. They didn’t try to create cells that could produce unnatural DNA on their own. Instead, they fed a chemical supplement to bacteria—a common laboratory strain of Escherichia coli—to give the cells some help.
Supplied with the dietary supplement, the bacteria readily replicated the artificial DNA, neatly combining the two synthetic characters into a new base pair, and then built that unnatural base pair into the structure of its DNA molecules, the scientists said.
By design, the new DNA didn’t change the basic functions of the altered cells, though they did grow slightly more slowly, the scientists said.
The technique also builds in a safety feature. Without the chemical additive, the bacteria stop making the artificial DNA and revert to normal.
“It is a way to make things safer,” said biochemist Eric Kool at Stanford University, who also wasn’t part of the research team. “It is much harder for the DNA to escape the lab and function in another organism.”
The Scripps Research Institute has licensed the process to Synthorx Inc., a new company launched with startup funding from two California-based venture-capital firms, Avalon Ventures and Correlation Ventures. Dr. Romesberg is a co-founder.
Company President Court R. Turner said they first need to make the process easier and more efficient. They plan to pursue health applications, including drug discovery, screening of new antibiotics and development of cancer diagnostics and therapeutics.
“We view this as groundbreaking technology,” said Mr. Turner. “Our initial goal is to optimize the system.”
Write to Robert Lee Hotz at Lee.Hotz@wsj.com
Corrections & Amplifications
Through a series of biochemical reactions, DNA uses amino acids to make proteins. An earlier version of the graphic accompanying this article incorrectly said that DNA makes amino acids to produce proteins. (May 19, 2014)