Chapter 1: The Obsession with Discovery

There was once a scientist who dedicated herself to her lab for countless hours, driven by the pursuit of a major breakthrough. This level of commitment can easily morph into an obsession, particularly when a significant discovery seems imminent. The anguish of being scooped—losing the race to be the first to unveil a finding—can render years of work seemingly futile.

While I have never experienced being scooped in my 25 years as a scientist, the concept intrigues me. The phenomenon of being scooped illustrates the tension between two powerful motivators in science: curiosity and ego. The exhilaration of uncovering an answer to a long-held question is often accompanied by the crushing realization that someone else has claimed the honor of discovery.

A particularly captivating case involves the unraveling of DNA's genetic code. Sydney Brenner and Francis Crick—two of the 20th century's most brilliant geneticists—dedicated their efforts to this problem from 1953 to 1961, only to be surpassed by a relatively obscure American biochemist.

In 2010, historians unveiled Brenner's letters and lab notes, revealing some of Crick's previously lost documents. It became apparent that despite being scooped, their reactions reflected a sense of excitement.

To delve deeper, I sought out Brenner himself. Finding him proved challenging; he operates labs in Singapore, Okinawa, Virginia, and California, and is frequently on the move. Eventually, I connected with an assistant who hadn’t seen him in years but could help. Fortunately, we both had plans to be in England shortly thereafter.

"Come in!" he exclaimed as I entered his home. At 88, Brenner remains one of the founding figures of molecular biology, sporting a Santa Claus-like appearance with his bushy eyebrows and warm grin. However, he is unflinchingly honest about scientists he deems unworthy. Despite his physical age, his intellect is as sharp as ever. I was grateful I had revisited many of his pioneering articles from the 50s and 60s to keep pace with him.

We settled in a cozy room filled with plants while his stepson prepared lunch. As a pioneer in molecular biology, Brenner could have pursued wealth but prefers to discuss science passionately rather than finances. His modest home reflected this attitude; I felt somewhat oversized in the quaint kitchen, which boasted open shelves filled with dishes.

Brenner began to recount how he first became captivated by the coding challenge. A protein consists of hundreds of amino acids, akin to beads strung together. With only 20 types of these beads, their arrangement dictates the protein's shape and function. Prior to the early 1950s, many believed proteins were simply chaotic polymers, but by 1953, it was established that they had defined sequences.

The central puzzle was how DNA, with its four-letter code (A, T, G, C), translated into these proteins. The challenge was evident: one letter could only represent a fraction of the amino acids. Combining two letters yielded only 16 combinations, while three letters produced 64—more than sufficient to encode 20 amino acids.

Consider the complexity of translating a protein, like insulin, from its DNA sequence, which remained unknown in 1953. This didn’t deter researchers; theoretical physicist George Gamow proposed a model where amino acids fit into diamond-shaped holes in the DNA structure. However, Brenner and Crick criticized this approach, recognizing the importance of DNA's directional nature.

Despite Gamow’s errors, his ideas sparked new ways of thinking about information transfer in biological processes. This shift in perspective spurred Brenner and Crick to explore the intricacies of the genetic code.

In February 1957, Crick proposed a mechanism for how the cellular machinery interprets DNA sequences. Even without punctuation, an English sentence composed of three-letter words can be deciphered, showcasing the potential for similar structures in DNA. Crick theorized that "sense" words could establish a reading framework for protein synthesis.

He identified that certain combinations of letters could not serve as sense words, narrowing down the possibilities. While his approach was initially promising, it ultimately proved incorrect, as most combinations are functional.

In 1958, Brenner made a significant leap toward practical experimentation with DNA. Considering the effects of a dye called proflavin on DNA, he hypothesized that it could induce single-letter additions or deletions, disrupting the reading frame. This pioneering approach enabled them to predict the structural implications of these changes.

As their work progressed, they discovered that combining certain mutants could restore the reading frame, suggesting that the DNA code was composed of three-letter words. The excitement of their findings propelled them forward, leading to long days and nights in the lab.

Then, in August 1961, the landscape shifted dramatically. At the International Congress of Biochemistry in Moscow, Crick learned from a colleague that the genetic code's first word had been uncovered by an unknown American biochemist, Marshall Nirenberg. His method involved feeding a repeated letter into a protein synthesis system, resulting in a protein made entirely of one amino acid.

This news was a double-edged sword for Crick. While it marked a monumental achievement in science, it also rendered much of his and Brenner's work obsolete. Ideally, I would like to think I would have welcomed the news graciously, as many scientists do in the face of competition.

However, Crick's response was exemplary. He invited Nirenberg to present his findings to a larger audience, showcasing a commendable spirit of collaboration. The audience was "electrified" by Nirenberg's revelation, and Crick's reaction was one of joy rather than disappointment.

The following interactions between Crick and Nirenberg demonstrated a mutual respect for each other's contributions to the decoding project. Brenner echoed this sentiment, reflecting on their excitement at finally having clarity on a crucial question in biology.

The impact of Nirenberg and his team's work cannot be overstated; it laid the groundwork for many advances in modern biology. Even today, it serves as a foundation for countless discoveries, akin to the periodic table's significance in chemistry.

Despite the competitive nature of scientific research, the remarkable reactions of Crick and Brenner exemplify the spirit of scientific inquiry. As Brenner advised, "Do the best experiments you can, and always tell the truth. That's all."

Bob Goldstein is a distinguished professor at the University of North Carolina at Chapel Hill.

Originally published at Nautilus on February 26, 2015.

Chapter 2: The Value of Collaboration

Section 2.1: The Emotional Toll of Competition

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Subsection 2.1.1: Navigating the Landscape of Discovery