LSD, DNA, PCR: the strange origins of a biological revolution
Before the COVID-19 pandemic, you may not have known about polymerase chain reaction (PCR) unless you worked in a lab that used it. Even then, you may not know the wild history of its origins.
PCR has a wide range of applications – from disease testing, criminal investigation, paternity testing and even human genome sequencing. Basically, wherever scientists work with DNA, there’s a good chance that PCR is involved.
PCR can take a tiny amount of DNA that would be very difficult to study and amplify it again and again in much larger quantities, which makes it easier to study. Before the invention of PCR, this process was long and laboriouswith scientists using cloning to amplify dna in bacteria.
It’s considered a revolutionary technique, summed up in this reverential ode.
The person credited with inventing PCR is Dr. Kary Mullis, for which he won a share of the 1993 Nobel Prize in Chemistry.
“In the midst of being extremely charming, he could be extremely abusive”, his friend and colleague, Dr Thomas J White told the New York Times. During an interview with Squire, Mullis repeatedly touches the interviewer and tries to convince her to sleep with him, even after he says no. She would describe later him as “outrageous” and “nasty”.
He also had his fair share of weird (and downright wrong) scientific opinions – for example, he didn’t believe that humans cause climate change or that HIV causes AIDS. These partner’work points out that he often makes mistakes with basic biology when coming up with ideas.
As he says in his book Dancing naked in the mental field, Mullis was driving his silver Honda through California, heading from Berkeley to his cabin in Anderson Valley. It was a Friday. At that time, Mullis was working at Cetus, a biotechnology company. He worked with oligonucleotides: short chains of nucleotides, which are the building blocks of DNA and RNA.
As he drove, his brain started to get creative. “Strings of DNA coiled and floated. Ominous blue and pink images of electric molecules injected themselves somewhere between the mountain road and my eyes,” he recounted.
Mullis declared that he was “functionally sober” at this point – however, his famous love to take and do the psychedelic drug LSD gives these colorful scenes a whole new context. In reality, he once said “Would I have invented PCR if I hadn’t taken LSD? I seriously doubt it […] I could sit on a DNA molecule and watch the polymers go by. I learned this partly through psychedelic drugs.
Albert Hoffman, who discovered LSD, said that Mullis personally told him that the psychedelic helped him bring up the concept of PCR.
As DNA danced through his mind, Mullis thought of how two oligonucleotides might stick at either end of a short area of interest in a relatively large chain of genetic material.
His background in computer programming also surfaced, and he began to think about how to apply an iterative mathematical procedure to this process. This would mean that after the area of interest has been marked by the oligonucleotides, the natural tendency of DNA to replicate could be exploited to replicate that area of interest over and over and over and over again.
Mullis stopped the car, pulled off the road, and began scribbling his ideas on an envelope with such enthusiasm that he broke the lead of his pencil.
This cerebral idea did not stay in the driver’s seat of his car. Mullis wrote that “We got to my cabin and I started drawing little diagrams on every horizontal surface that would take a pen, pencil or crayon, until dawn.”
Now he had to prove his idea.
He presented his ideas at a Cetus seminar in August 1983to a skeptical response.
“People don’t believe things, usually, for the right reasons,” Mullis said in a Google Tech Talk in 2010. “The reason they didn’t believe it was because of the fantastic result. Not because any of the steps were unlikely to work.
“He got a lot of data but he had personal issues and had a tendency to experiment out of control, so it wasn’t very convincing when he got a result,” Dr White told the New York Times.
In fact, his first PCR attempt failed. He had attempted to use the technique to amplify a fragment of human nerve growth factor, the sequence of which had recently been published. However, cetus scientists persisted for months alongside Mullis to create a suitable experimental system to make it work.
Mullis writes that the first successful attempt at PCR was on December 16, 1983. His colleague Fred Faloona had helped set up the reaction. Rather than using human DNA, Mullis had decided to use a plasmid, a simpler type of bacterial DNA.
The process would be to finish using Taq DNA polymerase, an enzyme of a bacterium find in Yellowstone National Park hot springs called Thermus aquaticus. This is important because high temperatures are required with each round of DNA amplification, and Taq DNA polymerase can withstand heat. Thanks to its role in PCR, the enzyme was crowned “Molecule of the Year” by Science in 1989.
In 1985, the team published an article in the journal Science describing how they used PCR to amplify human DNA as a potential way to diagnose sickle cell anemia.
However, Dr. Mullis left Cetus in 1986. He had been paid $10,000 for his part in discovering the PCR, but that was nothing compared to the $300 million Cetus sold the rights to five years later.
As Kary Mullis wrote in his book, “It would spread to every biology lab in the world. I will be famous. I would receive the Nobel Prize. It was a perfectly correct idea.