How machines help us decipher our genes
Back in the 1990s, I toured MIT’s Whitehead Institute in Cambridge, Mass., one of the key players in the Human Genome Project. The massive project was the life sciences equivalent of putting people on the moon. In a large room, rows and rows of big beige machines, automated gene sequencers, hummed along, churning their way through DNA. If this was a scientific revolution, it was a very quiet one.
That quiet belied the decades of human sweat and technological innovation that made it possible to identify and catalog the genetic instructions for a human. But Tina Hesman Saey, a senior writer and molecular biology reporter for Science News, remembers the effort required all too well.
When Saey started working in laboratories as an undergraduate, scientists identified the bases in DNA sequences through a laborious process. The work required her to be part short-order cook, part chemist, part X-ray technician and part medieval scribe. Tasks involved heating polyacrylamide in a microwave to make sheets of gel more than 300 millimeters across and just a few millimeters thick, adding bits of DNA tagged with radioactive isotopes and using electric current to push DNA molecules through the gel, with smaller molecules moving faster than larger ones. Next, the gels had to be doused with chemicals and exposed to giant cassettes of X-ray film, and the film had to be developed. “I used to have nightmares that something went wrong and I couldn’t get into the darkroom to develop my film,” Saey told me.
The end result was X-ray film laddered with black and gray smudges — DNA bases that a person then had to manually identify and record, one at a time. “You would just go along taking it from the bottom,” Saey says, “following each step up the ladder to determine the sequences.”
On a good day, Saey could identify 50 to 100 bases on one gel. Now, robots and automated high-throughput sequencers make it possible to read millions of bases at a time, with computers ID’ing the bases and packaging the data in a tidy digital file. “The robots took over all the tedious precision work,” Saey says. “People were freed up to do the analytical work.”
In this issue, Saey talks with Eric Green, director of the National Human Genome Research Institute, about the origins of the Human Genome Project and what remains to be discovered. The answer: plenty.
Among the many surprises that emerged from the project is how much we didn’t know about our DNA, including the importance of what before had been thought to be mere “junk” DNA. It’s a delight to see Green and Saey geek out over their fascination with noncoding RNAs, and their excitement over the many mysteries to be explored. I also learned that they worked in laboratories on the same hallway while Saey was a graduate student at Washington University in St. Louis. It’s a small world.
This conversation about the genomics revolution is part of our Century of Science project, which celebrates the 100th anniversary of Science News by exploring key scientific advances. There’s plenty more to marvel over at Century of Science.