Science Education

From Rags to Riches: A Tale of the Little Enzyme that Could

When I worked in forensics, we had access to a boiling water tap as a way to bypass the kettle when making tea. Little did I know that our instant hot water dispenser was potentially worth 450 million dollars.

The story starts with ecology.

Yawn.

I know. Most people dislike ecology. But trust me: this is a story of money, medicine, and life thriving in hellish conditions.

Microbial ecology was what Thomas D. Brock wanted to study so, unlike the contemporary picture of the labcoat-clad scientist in the air-conditioned lab, he ventured out to Yellowstone National Park to study microorganisms which can photosynthesize. Photosynthesis is the process by which plants will use the energy from the Sun to transform the carbon dioxide we exhale into oxygen and sugar. Certain microorganisms are also capable of this vital feat and Dr. Brock was studying those in the hot springs of the national park.

By chance, Dr. Brock noticed the presence of filamentous bacteria in particularly hot effluents of certain springs, microorganisms which lived at a toasty 82 to 88ºC. To give you an idea, this is a tad hotter than the water temperature at which experts recommend to brew delicate white tea. At the time, the highest temperature at which life was known to be possible on Earth was 73ºC. This was a significant discovery but not necessarily a lucrative one.

It was from Mushroom Spring in Yellowstone National Park that Dr. Brock and his team isolated Caldobacter trichogenes, a new genus of bacteria that thrived in boiling water. On the Celsius scale, water boils at 100ºC. The year was 1966. Mao Zedong had just begun the Cultural Revolution in China; Star Trek had aired its first episode on American television; and the Vietnam War was on-going in spite of numerous protests. Little did Dr. Brock know that C. trichogenes would revolutionize science.

This bacterium, an “extremophile” in that it grew in extreme conditions, was cultured in the laboratory and Dr. Brock’s team showed that its enzymes, the proteins that catalyze biochemical reactions, could indeed survive boiling temperatures. Funnily enough, one did not need to travel to Yellowstone National Park to come into contact with this extremophile; indeed, it was also found in the hot water system of a building on the campus of Indiana University where Dr. Brock taught.

All right. His team proved that life could exist in boiling water. Big deal. How did this discovery revolutionize molecular biology?

Fast forward twenty years later. A technique called the “polymerase chain reaction” (or PCR) was devised in a Californian biotechnology company called Cetus. (Who exactly came up with the concept and whether or not it heavily borrowed elements that had been previously published is an argument for another time) The game-changing PCR would allow a scientist to make millions of copies of a particular section of the genome, a feat which would soon burst open the doors for a molecular biology explosion.

When David Gelfand of Cetus needed an enzyme for the polymerase chain reaction which could withstand the near-boiling temperatures required to separate the two DNA strands, he tested many extremophile cultures available to him. The best one? The enzyme isolated from C. trichogenes.

In 1991, Swiss pharmaceutical company Hoffman-La Roche paid a whopping $300 million for the patents covering PCR and the enzyme isolated from C. trichogenes. In 2007, when I was using the boiling water tap at work, that amount of money was already worth $450 million. It is not unlikely that the lucrative extremophile ended up in my cup of tea.

This is not quite the end of the story.

I lied.

The bacterium was never officially called Caldobacter trichogenes. Dr. Brock, upon revising his initial manuscript, thought the name, which was derived from the Italian caldo for “hot” and the Greek tricho for “filament”, was “too fanciful”. The published article bore the new and commonly used name for the organism: Thermus aquaticus. The enzyme it uses to replicate its DNA is now known as Taq.

Scientists use Taq to amplify their region of interest in a DNA molecule so as to increase the signal-to-noise ratio. If you photocopy page 37 of a given book a million times, you’d be hard-pressed to find the original book in the final pile. Likewise, Taq-based PCR allows to drown out the original genome and only work with the piece of interest. It is used in forensic biology to match crime-scene evidence to perpetrators. It is used by molecular pathologists to identify cancer-causing mutations and identify weak points in existing tumours. It was even used to help sequence the human genome.

Fundamental research, such as the study of photosynthetic microorganisms at Yellowstone National Park by Dr. Brock in the 1960s, can sometimes seem irrelevant and not worth funding. Indeed, this is the stance that our Conservative government in Canada has taken. If it’s not meant to make money, it’s worth cutting out. This attitude dismisses the randomness of scientific appropriation: the discovery of hot-spring bacteria in the 1960s led to a molecular medicine revolution twenty years later. Science funding agencies cannot afford to be nearsighted. Do they really believe they can predict the future?

 

(Feature picture by Nic McPhee)

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One thought on “From Rags to Riches: A Tale of the Little Enzyme that Could

  1. Pingback: #22 ‘A Taq’ | lopsidedlablife by et Al.

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