Sorcerer of the Sequencer

Bob Blakesley, Director of the NISC Sequencing Group, Retires

BY JEANNINE MJOSETH, NHGRI

Genomics research is a quintessential team science. Contributing to each project are those who identify the scientific questions, collect biological samples, purify and sequence the DNA, and analyze the resulting data. The National Institutes of Health lost a key member of its broader genomics team with the December 31, 2015, retirement of Robert Blakesley, who was the director of the sequencing group at the NIH Intramural Sequencing Center (NISC) in Rockville, Maryland.

Blakesley came to NIH in after having spent more than 20 years in the biotechnology industry, where he oversaw the creation of an automated DNA-sequencing machine for medical diagnostics and directed new product development.

“When I recruited him to NISC in 2000, I knew that we would benefit from someone with his seasoned private-sector experience, deep technical expertise, good judgment, and calm, mature personality,” said Eric Green, director of the National Human Genome Research Institute (NHGRI), who had established NISC in 1997. In recognition of Blakeley’s contributions, Green awarded him the NHGRI Director’s Distinguished Service Award at the institute’s 2015 scientific symposium.

The scope of what Blakesley has accomplished on behalf of numerous intramural researchers is nothing short of epic. Between 1998 and 2012, NISC generated more than 57 million DNA-sequence reads for 76 researchers using the Sanger dideoxy sequencing method. That figure has spiked in the past six years with the introduction of next-generation DNA sequencing: During that time, NISC generated 2,151 billion sequence reads for 20,593 unique DNA samples contributed by 126 researchers at 15 NIH institutes and centers.

Blakesley’s achievement goes beyond the sheer quantity of sequence data: His group has attained a 90 percent success rate in generating sequence data from DNA samples accepted for study.

“He demand[ed] the highest possible quality all the time,” said NISC Deputy Director Alice Young, who has worked with Blakesley since 1990, first at Bethesda Research Labs (BRL; renamed Life Technologies, Inc., while he was still there) and now at NISC. “He takes a lot of personal pride in his work, so everybody who works with him has the same pride and ownership.”

Fifth-Generation Californian

Blakesley is a fifth-generation Californian. His maternal great-great-grandfather was born in 1854 in Woodbridge, San Joaquin County, California. His great-grandfather was an orange rancher in southern California. His grandfather, a mechanical engineer, supplied materials used in the state’s oil fields. And Blakesley’s father was an electrical engineer who developed a distance-sensing radar system that enabled the Apollo space mission’s lunar modules to make soft landings on the moon.

“We had a workshop in our garage when I was growing up,” said Blakesley. “My father was always figuring something out, making new tools, or building electronic devices. I absorbed his desire to understand how things work and to build tools.”

As a child, Blakesley assembled model cars and radio-controlled planes for which he built his own controllers. By the time he reached high school, he had even built his own stereo system. A turning point came in the fall of 1963 when he read a long Los Angeles Times article about the 10th anniversary of the famous Francis Crick and James Watson discovery of the double-helical structure of DNA.

“Once I read that article, I wanted to know how genes worked,” Blakesley said. “It kick-started me and drove my education and career.”

He received his undergraduate degree in biochemistry from the University of California, Berkeley, and his Ph.D. in biochemistry at Michigan State University in East Lansing, Michigan. At Michigan, he learned to make his own reagents to study the kinetic and physical properties of polymerases.

Recruited by Bethesda Research Labs

A career crossroads presented itself while he was working as a postdoctoral fellow at the University of Wisconsin at Madison. Blakesley was the only one in the laboratory when a sales representative from BRL called and tried to sell him restriction enzymes.

“I told him that I make my own,” Blakesley recalled. The conversation eventually led to a job offer from BRL to oversee a research group that would develop an automated DNA-sequencing machine for medical diagnostics.

“That hooked me,” he said, adding that at the time, biochemists Frederick Sanger and Walter Gilbert (who shared the 1980 Nobel Prize in Chemistry with Paul Berg for their contributions to determining the base sequences of nucleic acids) thought that DNA sequencing might be important to medicine. “That was the challenge that got me interested in the company.”

BRL was first located in a 500-square-foot office and storage room in Gaithersburg, Maryland. Half of the space was used as a laboratory, and enzyme purifications were performed in a small beer cooler. “We often left the office door open because the air conditioner didn’t work well,” said Blakesley. “A huge dog from the next-door veterinarian clinic would often wander in to check our progress.”

It was an exciting time to direct new-product development for a start-up company. “We really listened to our customers, were as efficient as possible, and paid attention to detail. In the end, we delivered to them what they needed,” said Blakesley, who patented 10 products and procedures and introduced more than 150 products during his 23 years in private industry.

BRL grew quickly and eventually seemed to focus less on customers and more on profit. Increasingly frustrated, Blakesley contacted Green to ask whether he knew of any career opportunities. NISC, the nascent NIH organization that provided DNA-sequencing services on a cost-recovery basis, needed someone with industry experience.

“Bob was one of the best hires I ever made,” said Green. The admiration is mutual: Blakesley credits Green for his unwavering support and for valuable introductions to those working in the large genome-sequencing centers around the world.

“NISC benefited a lot from collaborating with bigger groups that have successfully tackled big projects,” said Blakesley. “We were in almost constant contact with the large genome-sequencing centers at Washington University, the Broad Institute, and Baylor College of Medicine. When we ran into a problem, we called them up and asked how they solved it. I don’t think we could’ve gotten to where we are today without those interactions.”

The exchange has been a two-way street. Like a good team member, NISC shared its information with the other centers. “The real benefit to team science is that you can solve very complex problems by collaboration, by bringing in people from different disciplines,” said Blakesley. “I’m most proud of our collective successes at NISC. We have a fine group of individuals who work very hard and care about each other. I was sad to leave.”

Blakesley’s future plans revolve around his family. “I want to spend more time with my three kids and my six grandkids,” he said. “I’d like to spend time on genealogy, woodworking, gardening, and organizing the piles of 35-millimeter color slides and thousands of digital photos that have been stacking up.”

Whatever Blakesley’s direction, he will exceed all expectations just as he has at NISC, said Young. “He has really high standards for everything. It’s his nature.”