At Jef Boeke’s lab, you can whiff an odor that seems out of place, as if they were baking bread here.
However, he and his colleagues are cooking up something else altogether: yeast that works with chunks of man-made DNA.
Scientists have long been able to make specific changes in the DNA code. Now, they are taking the more radical step of starting over and building redesigned life forms from scratch.
Illustration: Mountain People
Boeke, a researcher at New York University (NYU), directs an international team of 11 labs on four continents working to “rewrite” the yeast genome, following a detailed plan they published in March.
Their work is part of a bold and controversial pursuit aimed at creating custom-made DNA codes to be inserted into living cells to change how they function or even to provide a treatment for diseases. It could also someday help give scientists the profound and unsettling ability to create entirely new organisms.
The genome is the entire genetic code of a living thing. Learning how to make one from scratch, Boeke said, means “you really can construct something that’s completely new.”
The research may reveal basic, hidden rules that govern the structure and functioning of genomes. However, it also opens the door to life with new and useful characteristics, such as microbes or mammal cells that are better than current ones at pumping out medications in pharmaceutical factories, or new vaccines.
The right modifications might make yeast efficiently produce new biofuels, Boeke said.
Some scientists look further into the future and see things such as trees that purify water supplies and plants that detect explosives at airports and shopping malls.
Also on the horizon is redesigning human DNA. Though, the intention is not to make genetically altered people, scientists stress.
Instead, the synthetic DNA would be put into cells, to make them better at pumping out pharmaceutical proteins, for example, or perhaps to engineer stem cells as a safer source of lab-grown tissue and organs that can be transplanted into patients.
Some have found the idea of remaking human DNA disconcerting, and scientists plan to get guidance from ethicists and the public before they try it.
Still, redesigning DNA is alarming to some. Laurie Zoloth of Northwestern University, a bioethicist who has been following the effort, is concerned about making organisms with “properties we cannot fully know.”
The work would also disturb people who believe creating life from scratch would give humans unwarranted power, she said.
“It is not only a science project,” Zoloth said in an e-mail. “It is an ethical and moral and theological proposal of significant proportions.”
Rewritten DNA has already been put to work in viruses and bacteria. Australian scientists recently announced that they had built the genome of the Zika virus in a lab, for example, to better understand it and get clues for new treatments.
At Harvard University, Jeffrey Way and Pamela Silver are working toward developing a harmless strain of salmonella to use as a vaccine against food poisoning from salmonella and E. coli, as well as the diarrhea-causing disease called shigella.
A key goal is to prevent the strain from turning harmful as a result of picking up DNA from other bacteria. That requires changing its genome in 30,000 places.
“The only practical way to do that is to synthesize it from scratch,” Way said.
The cutting edge model for redesigning a genome, though, is yeast. Its genome is bigger and more complex than the viral and bacterial codes altered so fa, but it is well-understood and yeast will readily swap synthetic DNA for its own.
Still, rewriting the yeast genome is a huge job.
Similar to a chain, it has 12 million chemical links known by the letters A, C, G and T. That is less than one-hundredth the size of the human genome, which has 3.2 billion links.
However, it is still such a big job that Boeke’s lab and scientists in the US, Australia, China, Singapore, and the UK are splitting up the work. By the time the new yeast genome is completed, researchers will have added, deleted or altered about a million DNA letters.
Boeke compares a genome to a book with many chapters, and researchers are coming out with a new edition, one with chapters that allow the book to do something it could not do before.
To redesign a particular stretch of yeast DNA, scientists begin with its sequence of code letters — nature’s own recipe. They load that sequence into a computer then tell the computer to make specific kinds of changes. For example, one change might let them rearrange the order of genes, which might reveal strategies to make yeast grow better, NYU researcher Leslie Mitchell said.
Once the changes are made, the new sequence is used as a blueprint. It is sent to a company that builds chunks of DNA containing the new sequence. Then, these short chunks are joined together in the lab to build ever longer strands.
The project has so far reported building about one-third of the yeast genome. Boeke hopes that the rest of the construction will be done by the end of the year. But he says that it will take longer to test the new DNA and fix problems and to finally combine the various chunks into a complete synthetic genome.
Last year, Boeke and others announced a separate effort, what is now called Genome Project-write or GP-write. It is chiefly focused on cutting the cost of building and testing large genomes, including human ones, by more than 1,000-fold within 10 years. The project is still seeking funding.
In the meantime, leaders of GP-write have started discussions on ethical, legal and social issues. They realize that the idea of making a human genome is a sensitive one.
“The notion that we could actually write a human genome is simultaneously thrilling to some and not so thrilling to others,” Boeke said. “So we recognize this is going to take a lot of discussion.”
This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.
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