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PCR is one of the most useful methods in biology, and in your Class 12 biotechnology chapter it takes up only a paragraph and a figure. Behind that figure is a chemist who worked at a biotechnology company making short pieces of DNA, and an idea that came to him on a drive. This post covers Kary Mullis's path, how PCR works, what the first papers actually reported, and a calculation the textbook does not show: working backwards from how many copies you got to how many cycles you needed.
Who was Kary Mullis?
The Nobel facts page records that he was born on 28 December 1944 in Lenoir, North Carolina, and died on 7 August 2019 in Newport Beach, California. In his Nobel autobiography he writes that he took a BS in chemistry at Georgia Tech, where he learned "most of the useful technical things, math, physics, chemistry" he later used, and then a PhD in biochemistry at Berkeley under J. B. Neilands.
By the early 1980s he was working for Cetus, a California biotechnology company, making oligonucleotides, the short single strands of DNA that act as primers. One spring night, driving to a cabin he was building in northern California, he writes, "I came across the polymerase chain reaction." The 1993 press release also records that he got the idea during a night drive in the Californian mountains.
He received half of the 1993 Nobel Prize in Chemistry "for his invention of the polymerase chain reaction (PCR) method". The other half went to Michael Smith for site-directed mutagenesis.
How does PCR work?
The press release describes the steps. Two short oligonucleotides are made so that they bind to opposite strands on either side of the DNA segment you want. A DNA polymerase starts at these primers and builds new strands. Heating separates the strands so they can be copied again, and each repeat doubles the number of copies of the chosen segment.
The NCERT Class 12 biotechnology chapter names the three steps of each cycle: denaturation, primer annealing and extension. It notes that repeated amplification is possible because of a thermostable DNA polymerase from the bacterium Thermus aquaticus, which stays active during the high temperature used to separate the strands.
What did the first papers report?
Two papers in Science, both with Mullis among the authors, show how the method grew.
In 1985, Saiki and colleagues used primer-directed enzymatic amplification of beta-globin DNA to build a fast prenatal test for sickle cell anaemia. They reported a 220,000-fold increase in target copies, and genotypes in less than a day from samples with well under 1 microgram of DNA.
In 1988, Saiki and colleagues used a thermostable polymerase from Thermus aquaticus. The abstract says it "greatly simplifies the procedure" and improved specificity and yield. Single-copy sequences were amplified more than 10 million times, segments up to 2,000 base pairs were copied, and a target present once in 100,000 cells was detected.
If you are revising the whole chapter, our guide to biotechnology principles for NEET covers restriction enzymes and vectors too.
Worked example: from copies back to cycles
With perfect doubling, copies after n cycles = starting copies × 2ⁿ. Textbook questions usually give n and ask for copies. Research papers report the fold increase, so it helps to go the other way: n = log(fold) / log 2.
The 1985 result. n = log(220,000) / log 2 = 5.342 / 0.301 ≈ 17.7. So a 220,000-fold increase equals about 18 perfect doublings.
The 1988 result. n = log(10,000,000) / log 2 = 7 / 0.301 ≈ 23.3, about 23 perfect doublings.
When doubling is not perfect. Suppose each cycle copies only 90 percent of the strands, so the multiplier is 1.9 rather than 2. After 20 cycles: 2²⁰ = 1,048,576, but 1.9²⁰ ≈ 376,000. A small drop in efficiency per cycle costs almost two-thirds of the product.
The Nobel presentation speech says more than 20 cycles produce over a million copies, which matches 2²⁰. Real reactions do not always double perfectly, as step 3 shows.
Common mistakes:
Using log base 10 and forgetting to divide by log 2.
Writing 2 × n instead of 2ⁿ.
Assuming every cycle doubles exactly. Efficiency matters, as step 3 shows.
What can a student take from Mullis's way of working?
Combine known parts in a new way. Primers and DNA polymerase already existed. The idea was to use two primers and repeat the cycle.
Test the idea on a real problem. The first major paper applied PCR to diagnosing sickle cell anaemia.
Improve the weak step. The switch to a heat-stable enzyme made the method far easier to run.
Science is a team effort. Both key papers had several authors who turned the idea into a working method.
If logarithms are what slows you down here, the Fermi Concept Library covers every concept in mathematics and biology, each with its own lesson, so you can revise logs and DNA replication side by side. For how cells copy DNA in the first place, read our post on DNA replication and transcription.
Work out how many perfect cycles turn 50 copies into about 1.6 million, then check your answer with a calculator.
