Columbia University Medical Center

Tom Maniatis: A Deep Sense that Science Must Be Shared

Suddenly Everyone Had the Tools to Study How Cells Work

The fundamental molecules of life – DNA (genes), RNA, and proteins – were being studied in simple organisms such as bacteria and viruses, but it was not possible to study these molecules in more complex organisms, most importantly in humans. Human genes were still buried within DNA’s 3 billion base pairs, and the details of how certain genes lead to disease were completely concealed. Experts in the field expected slow, incremental growth in new knowledge.

Molecular Cloning manual cover

"It's impossible to overstate the impact this manual had on a rapidly expanding field."

But the invention of new recombinant DNA techniques, which allowed researchers to cut DNA from an organism, and paste it into a DNA molecule capable of replicating in bacteria (cloning vector), made it possible for the first time to isolate and study human genes and the proteins they encode. Major steps in this direction were provided by the development of methods for generating cDNA and genomic DNA libraries in the Maniatis lab.

However, these methods were technically complex, and required expertise that most biologists did not have. “The techniques were difficult for people who had never used them before,” Maniatis admits. “Most of this technology came out of labs in Boston or the San Francisco area. It was fine if you were there and could walk down the hall to get help, but otherwise the technology was hard to master.”

Jim Watson, director of Cold Spring Harbor Laboratory, asked Maniatis to teach the techniques during a summer course at CSHL, and afterward, produce a manual.

“At first I was reluctant [to write a manual]. I couldn’t really even imagine the value,” Maniatis said in a video produced by CSHL. “I thought, well, maybe it could be used by labs that do this work to train new students.”

But the manual quickly spread far beyond those few labs: partly because even complete novices, like a young Huda Zogbhi, could get the techniques to work. And partly because researchers in other fields, from medicine to agriculture, saw how they could benefit from the techniques.

Richard Axel, MD, Nobel laureate and University Professor in the Departments of Biochemistry & Molecular Biophysics and Neuroscience, and a good friend of Maniatis, sums up what happened next: “Molecular biology just took off. Suddenly everyone had the tools to study how cells work.”

NEXT:  Fundamental Discoveries of the Nature of Genes