Today ChemistryViews has great pleasure in presenting the first ever published interview with James Thermus (T.) Aquaticus, a Gram-negative rod-shaped bacterium with fascinating abilities. His enzyme Taq polymerase revolutionized molecular biology, genetics, forensic sciences, food technology, and many other areas in science and technology. While normally being rather reclusive, James T. Aquaticus agreed to be interviewed since he feels that his contribution to modern society is not fully appreciated.
You refused to meet us in any place but a sauna. Frankly, we are already feeling uncomfortable.
Believe me, I do too. With all these people storming in and out of the sauna, the temperature quickly drops to 60 °C or lower – really rather chilly.
I suggested this location since it is the only place I know where you ice-cold creatures are willing to expose yourself to somewhat normal temperatures.
Ahem, so let’s move on to the main part of our discussion: You have been involved in science for more than 40 years. What are you most proud of?
Basically, my enzyme, Taq polymerase, is at the heart of the Polymerase Chain Reaction (PCR). This started a revolution in biology, medicine, and forensic sciences, comparable only to other once-in-a-century such as Penicillin or the invention of the transistor. So it is fair to say that I have changed the world. But still nobody knows me: Any stupid pop star is recognized everywhere, but I’ve never been asked for an autograph, and I’ve never had hundreds of fans chasing me …
Can you please explain what exactly PCR is and what role your Taq enzyme plays?
See, this is part of the problem. You MUST have heard about it. It is now a central pillar of modern biology, countless scientific careers have been based on this method. This enzyme has made it possible to perform a myriad of tests … in genetics, modern forensics, food science, testing for pathogens, and even paternity tests. Essentially, we would live in a different world without it.
Also, the amazing breakthrough in sequencing ancient genomes like that of the Neanderthal or the Mammoth was only possible with PCR. So if anything like Jurassic Park becomes reality, it will only be possible thanks to my contribution!
Very impressive, but what exactly is PCR?
Like all really great inventions, the principle is very simple: PCR is an extremely efficient method for duplication or as we say amplification of pieces of DNA to generate many copies of it. The more copies of DNA you have, the easier it is to analyze.
The PCR consists of three steps run in a cycle: In a denaturation step the probe is heated to about 90 °C to split the double stranded DNA into two single strands. In a hybridization step at about 60 °C two very short pieces of DNA, so called primers, bind to the single strands. And in the polymerization step at about 70 °C my Taq polymerase synthesizes new double strands out of the single strands. It is directed by the primers. The steps are repeated until you have enough DNA.
Because my Taq polymerase is heat stable and does not become dysfunctional at 90 °C, as other enzymes would, the whole process runs after adding all of the substances in one go right at the beginning.
The method is so sensitive that genes can be amplified from a single molecule! What’s more, the amplification of any gene is fast and simple. And it allows researchers to introduce any point-mutation into a known DNA sequence.
his is a great accomplishment, yet you sound a tad bitter.
You know, I understand this is science and not business or banking. So I do not expect to have a golden parachute or a private jet, nor do I want to own 20 different houses and go to endless parties. Still, I have to admit that I was expecting some kind of recognition, maybe some sign of gratitude from the countless victims of crimes where PCR made it possible to identify the perpetrator, or from one of the thousands of researchers and students who only succeeded in their projects thanks to PCR and me.
I long had hopes that I would one day get a phone call from Sweden – but instead the Nobel Prize went to Kary Mullis in 1993. He didn’t even thank me!
Taq is required in huge amounts worldwide. Do you produce it all yourself?
No, of course not. That would be far too expensive.
I established how to produce Taq with Escherichia coli. You know E. coli, it is a really blasé and stupid bacterium normally living in shi….. oh, I beg your pardon … I mean in your intestines, for example, but it is a useful working horse for my purposes.
Let’s switch topics: you made PCR a really efficient method in 1983, but you’ve only just got around to talking about it in public. Why now?
In the past, although I wasn’t really appreciated, I was absolutely satisfied with my work in the lab. However, over the past few years colleagues have been showing me more and more that I am no longer necessary. They have replaced me with some stupid creeps. So, I decided to let the public know that without me the world would be a different place.
Can you please be a bit more precise here. Who are these “creeps”?
Taq is being replaced by enzymes from Archaea – a totally different form of life. They are very strange, not organisms like you and me, and totally different to us. There is nothing normal about Archaea, not their shape, their DNA, their ribosomes, not even their cell membrane. But they think they are better at producing polymerase enzymes. Very odd creatures indeed.
So why have their enzymes been chosen?
Because they are brainless law-abiding robots, with no creativity whatsoever! Their enzymes can copy more than 1 million bases without making a single mistake! If you want to associate with such robots, go ahead …
Isn’t high fidelity DNA replication essential in PCR?
(Interviewer’s note: the look on his face made my blood freeze, and for a split second it felt chilly in that steamy sauna. I decided to change the topic, again.)
What are your plans for the future?
I think it is time to look for new challenges outside the lab. I plan to go home as quickly as possible.
You come originally from Yellowstone National Park, USA, and used to live in the Lower Geyser Basin near the Great Fountain Geyser and White Dome Geyser, right?
Yes, I come from one of the most beautiful spots on earth which incidentally is also one of the most frequently visited tourist attractions on this planet. That has of course made it less pleasant than in the past, but at night, when all the cold-blooded hoards of monkeys are gone, and you are warm and cosy in the geyser, you often see a beautiful sky filled with millions of stars – that’s when I really feel at peace with the world.
James T. Aquaticus, thank you very much for this interesting conversation.
I assume you’re stopping the interview here because you think the sauna is too hot – ice-cold creatures …
James Thermus Aquaticus is more than a billion years old. He entered research very late, not until 1967, when he started working with Thomas Brock and Hudson Freeze at Indiana University, USA, on first experiments of live being sustainable at above 60 °C. In 1970 he contributed a thermostable aldolase to the scientific community and from the late 1970ties on, his restriction enzyme Tac1 was widely used in molecular biology. His big breakthrough came when he joined the lab of Kary Mullis, Cetus Corporation, Emeryville, CA, USA. From 1983 his DNA polymerase was used for the PCR technology. Mullis received the Nobel Prize for the development of PCR in 1993.
James Thermus Aquaticus has around 900 journal publications of which 51 papers are cited more than 100 times. He is mentioned in innumerable books.
The Taq polymerase was named Molecule of the Year in 1989 by the Science magazine and was the first molecule to have ever receive that honor.
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