GoKawiilI.
Writing is an act of discovery. Sometimes you sit down, intent on making a specific argument, only to find (upon deeper research) that the argument is garbage and doesn’t hold up to scrutiny! Writing has a beautiful tendency to reveal holes in one’s logic, as it did for this essay.
Initially, the goal was to make a long argument about how polymerase chain reaction, or PCR, hasn’t changed basically at all since 1987, when the first “modern” thermocycler machines were released. The thesis was that there must be many ways to make PCR significantly faster, cheaper, better. This argument is roughly correct, but not to the degree anticipated. Time-savings with new PCR technologies are modest, and scientists are reluctant to buy cheap PCR machines for a few reasons (more on that later).
And yet, this essay still seemed worth writing. The inspiration stemmed from two ideas submitted for the Fast Biology Bounties — from Sebastian Cocioba and “Utah” Hans — about plans to create photonic PCR machines. The gist of photonic PCR is that you can use LED lights or lasers to rapidly heat samples, thus running 40 cycles of DNA amplification in the span of 6 minutes. I gave out $3,500 in microgrants to support these ideas, courtesy of Astera Institute.
Faster PCR may not seem like a particularly desirable problem to work on. But it’s important for a few reasons. First, even a marginal improvement to a widespread method can have huge downstream effects on scientific productivity as a whole. And second, as more biology experiments get automated, and robots run these experiments 24/7, those time improvements will scale exponentially. Trimming 20 minutes off PCR may not be a big deal to human scientists, but it might matter a lot to robots!
It turns out, though, that many of my (weakly held) assumptions were quickly overturned. As exciting as photonic PCR seems, I think it’s unlikely to show up in academic labs anytime soon.
II.
PCR is a decades-old method to copy DNA. Millions of biologists use it nearly every week for everything from cloning genes to diagnosing diseases. The way it works is fairly simple, too. Just take a little tube and add a DNA sequence, or the molecule to be copied. Next, add a DNA polymerase enzyme and some primers, which are short DNA snippets that bind to the DNA sequence to be copied. And finally, sprinkle in some nucleotides (the raw building materials for DNA) and magnesium. Finally, place the tube inside a machine, roughly the size of a DVD player, called a thermocycler, the sole job of which is to ramp temperatures up and down, again and again.
The machine starts by increasing the temperature to about 96°C, which melts the double-stranded DNA molecule, breaking it into two separate pieces. Then, the temperature drops to 60°C, the perfect temperature for primers to latch onto those DNA molecules. Next, the device goes back up to about 70°C, the temperature at which the polymerase enzyme is most active. Each polymerase seeks out a primer, grabs onto it, and begins copying the DNA by stitching together nucleotides. And finally, the thermocycler goes back to 96°C to begin the cycle anew. Every time this cycle runs, the amount of DNA in the tube roughly doubles. There are typically 30 cycles in a single PCR experiment, which means that two strands of DNA become (assuming perfect efficiency) 230 copies, or 1.07 billion molecules.
How PCR works. From genome.gov.
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