History books are filled with the technical advances that made genetic engineering possible, from the discovery of enzymes that cut and paste DNA to the development of techniques for reading the sequence of genes.
But perhaps more than any other advance in molecular biology, it was a centuries-old technology – ink on paper, in the form of Tom Maniatis’ 1982 Molecular Cloning manual – that was responsible for igniting the revolution of recombinant DNA.
The manual – often referred to as “the Bible” by students and researchers — contained practically every technique biologists needed to know in order to manipulate DNA. With these techniques scientists could identify genes that cause disease and they could produce new drugs such as human insulin. Later, the techniques proved indispensable for the success of the Human Genome Project. Maniatis’ laboratory developed many of the techniques in the manual, and they were so clearly explained that complete novices to molecular biology could pick up the manual and get instant results.
“It’s impossible to overstate the impact this manual had on a rapidly expanding field,” wrote the publisher on the manual’s 25th anniversary. “Molecular Cloning was the book that really put the techniques in every lab’s hands. It opened a door for many researchers into the world of recombinant DNA technology and played a significant role in spreading these approaches through the scientific community.”
Maniatis, now the chairman of the Department of Biochemistry and Molecular Biophysics and Isidore S. Edelman Professor of Biochemistry, still seems surprised at the impact the manual has had around the world.
“I got an email the other day from Huda Zoghbi, who discovered the gene that causes a severe form of autism in young women [Rett Syndrome],” he said. “It’s amazing to me. Here’s this powerhouse researcher, a member of the National Academy of Sciences and a Howard Hughes investigator, who said she knew nothing about recombinant DNA when she got her first research position. But she told me she used the manual to write her first NIH grant (which was awarded).”
The manual (co-written with his postdoc Ed Fritsch and Joe Sambrook, then the scientific director of Cold Spring Harbor Laboratory) appeared at a tipping point in the history of molecular biology.