For Nobel Laureate Roberts, Serendipity Leads to Amazing Discoveries in Molecular Biology

Dr. Richard J. Roberts, Chief Scientific Officer at New England Biolabs and final speaker in the second series of AI seminars, Modern Artificial Intelligence at NYU Tandon, waxed philosophical for much of his presentation on December 11, 2018, weaving a discussion of science with a story of inspiration, passion, and good fortune in his journey from (nearly professional) billiards to molecular biochemistry.

Given that the series, the first of which took place in February this year, focuses on unifying scientific communities around influential ideas, he was the perfect choice to close the 2018 series, as his lecture was as much about unifying concepts as a driver for collaboration as it was about how he and his peers revolutionized the field and paved the way for genetic engineering. Coincidentally, his presentation took place a day after the 25th anniversary of his having won the Nobel Prize in Medicine in 1993 for his discovery of split genes and mRNA splicing in 1977.

A pioneer in the field of bioinformatics, Roberts also touched on areas of molecular biology in which AI and machine learning can play a major role — including at Boston-based New England Biolabs (which is currently looking for an AI expert).

Born in Darby, Derbyshire, England, during World War Two, Roberts lived on a street leading directly to a Rolls Royce factory, which happened to be a bombing target for the Luftwaffe. The fact that his side of the street had not been destroyed by bombing (no such luck for the other side of the street) is, he said, a recurring theme, revealing the importance of good luck.

He described how, to borrow a phrase, a “series of fortunate events” led him to inspiring episodes, teachers and mentors: his headmaster at St. Stephen’s School in Bath, who would hand Roberts a puzzle every day as he left school, inculcating in him at an early age a love for intellectual challenges; the chemistry set his parents bought for him that sparked an interest in the field when he was just 11; his mentor at Sheffield University in England, Kazu Kurosawa, with whom he finished his doctoral thesis work in only a year; and his discovery of the book, “The Thread of Life: An Introduction to Molecular Biology,” by John Kendrew.

“I’d heard a bit about molecular biology but the book was wonderful. By the time I’d finished, I knew that’s what I wanted to do. And it’s actually easy to switch fields,” he said. “If you see something you like, it’s not hard to switch. I moved from math to chemistry, from chemistry to biology, from biology to molecular biology, and into bioinformatics.”

After attaining his Ph.D., Roberts spent six weeks in the lab of Fred Sanger at Harvard, who had developed methods for sequencing DNA. There he began working on the mysteries of transfer RNA (tRNA), lead to a job at Harvard and at the famous Cold Spring Harbor laboratory of Jim Watson, co-discoverer of DNA, who asked Roberts to join the lab to sequence the DNA of the SV40 virus, a very small virus that causes cancer in humans. “But when I got there, there were two other groups doing it. It felt like a competition to me; I prefer collaboration.”

The work led to advances in the use of restriction enzymes, which can be manipulated to dice DNA into fragments, some quite small. Roberts began with RNA sequencing because it is easier to handle and therefore useful for developing a methodology.  

“It occurred to me that this was a great way to make small DNA for sequencing; restriction enzymes are everywhere, and they turned out to be the workhorses of the biotech revolution — they are used in cloning, for instance.”

Roberts found 75 varieties in the lab at Cold Harbor and suggested to Watson that they could launch a company selling these enzymes and use profits to support research. Watson’s response: “no.”

Undaunted, Roberts got involved with processes to look at promoters, a region of DNA that initiates transcription of a particular gene, located near the transcription start sites of genes. The idea was to examine messenger RNA using promoters to work out an easy way to separate pieces of the adenovirus.

Roberts’ discovery of RNA splicing in Adenovirus 2 Messenger RNA was published in the influential journal Cell, with a title that had “Amazing” in it to describe the discovery, an adjective typically inappropriate in a scientific paper.

“A gene is just straight piece of DNA, read three bases at a time. In eukaryotes, genes are split into pieces. Into order to get continuity, you have to splice pre-RNA so the bits that code for protein all come together. That’s splicing,” he explained. “It turned out that everywhere you looked you found this.”

Roberts began sequencing spliced junctions to work out what the code was that cells were using. In adenovirus there were so many places where this was happening Roberts had sequence the entire genome, which at the time wound up the second longest genome ever sequenced.

“At the time there were no computer programs that would take small DNA and hook them together. We had to write our own programs.” This was bioinformatics in its infancy.

Roberts, Knighted by Prince Charles in 2008, is also an activist, organizing other Nobel laureates for such causes as advocating for the release of a group of Bulgarian nurses who had been accused of spreading AIDS in Libya, which at that time was under the boot of Muammar Gaddafi. They were jailed, tortured and several were made to confess.

Roberts got more than a hundred laureates to send a letter to Gaddafi, urging him to release the nurses and explaining how they could not have spread AIDS. Gaddafi invited Roberts to Tripoli, where they met and Roberts convinced him of the nurses’ innocence. They were freed. “Having a Nobel prize means that lots of people will listen to you,” he said.

Yet, Roberts may well have become a professional billiards player, when he was 17, was bored with school and spending time at the local YMCA played snooker, and became so good he thought he might be thrown out of school, or quit.

While losing in a tournament one day he made a lucky shot, setting himself up for an easy, win. However, he was careless, and what should have been an easy coup de grâce.

“An older gentleman gave me advice after the match,” he recalled. “If you are going to be successful you have to take advantage of luck. Always take advantage of luck.”

His life was saved on two occasions by providence: Roberts was a recipient of one of five letters mailed by the Unabomber — his was one of those lacking an explosive device; and he was booked on one of the flights hijacked by terrorists on September 11, 2001. When the meeting to which he was traveling was rescheduled he wound up on the same flight, but a day earlier.

Luck in the lab requires perspective, he explained. Some may see incorrect results as bad fortune, but Roberts thinks of it as the best of luck.

“You want to do experiments that don’t work out because those results are nature trying to tell you something. Occasionally you want things that don’t work out.”

Next year, a third iteration of the AI seminar series beginning February 8, 2019, will feature Martial Hebert, expert in computer vision and perception for autonomous systems at the Robotics Institute of Carnegie Mellon University; Tony Jebara, director of machine learning research at Netflix; Manuela Veloso, head of machine learning at Carnegie Mellon; and Eric Kandel, winner of the Nobel Prize in physiology, and one of the most influential neuroscientists of our time.