Free Radicals - Michael Brooks [8]
Einstein relied on inspirations that had no traceable source. Working everything out logically, by deduction, is ‘far beyond the capacity of human thinking’, he said. Looking back on his experience, and relating it to the history of science, he admitted that ‘the great steps forward in scientific knowledge originated only to a small degree in this manner’. That is something that Kary Mullis, another drug-using Californian, would agree with wholeheartedly. Mullis won the 1993 Nobel Prize in Chemistry, and he says he couldn’t have done it without LSD.
Late one Friday night in May 1983, Mullis was driving along a Californian highway. His girlfriend was asleep beside him in the passenger seat. As can happen when you are driving, his mind was not really on the road. ‘DNA chains coiled and floated,’ he says. ‘Lurid blue and pink images of electric molecules injected themselves somewhere between the mountain road and my eyes.’
DNA has a glorious mystique these days, but really it is just a complicated molecule. You can think of it working rather like Velcro: it is composed of two strands that stick together. Unlike Velcro, DNA has four different kinds of hook, which are known as A, T, G and C – abbreviations of their chemical names. Each hook can link to only one other kind: A links to T, and G links to C. When they are strung along one strand of the molecule, the order of the hooks – A, C, C, G, T, A, and so on – dictates what the other strand must look like in order for it to stick. This order also encodes the instructions for making specific proteins, the building blocks of biology.
In a biological organism, the DNA must make copies of itself, and it does this by pulling the two strands apart and bringing in new hooks to pair with the exposed ones. In this way, each single strand generates a new partner.
Kary Mullis was a humble hook-maker: he was producing the chains of acids that constitute DNA’s A, T, G and C molecules. Despite his relatively lowly position in the Cetus Corporation, a biotechnology company based near Berkeley, he would habitually apply his mind to the bigger picture. He liked to imagine that one day we would understand the four-letter alphabet of the genetic code well enough to find where the copying had gone wrong and mistakes had crept in. If you could read the copying mistakes that lead to diseases such as Huntington’s disease or sickle-cell anaemia, for example, you could potentially correct them, or at least avert the problems they cause. That’s why Mullis would spend time throwing around ideas about how that might be done.
It’s not an easy task. A strand of human DNA contains around a billion of the A, C, G and T hooks, or ‘bases’. That’s a daunting amount of reading to be done, especially when the writing is of a size where the book fits inside the microscopic nucleus of a biological cell.
But, Mullis reasoned, you don’t have to read it all at once. He could assemble a single synthetic strand of just twenty bases, pull apart the strands of the DNA under investigation, and see if his synthetic strand fitted anywhere along it. If it did, you could encourage that little synthetic strand to reproduce itself by giving it some more bases, and the right enzymes and conditions to do the job. Do it enough times and you’d have a beakerful of copies of your strand. In a process reminiscent of what happens when Alice takes a bite of the ‘Eat me’ cake in Wonderland, that fragment of DNA would grow from the microscopic scale to the proportions of our world. Then you produce another short synthetic strand with a different sequence of bases, and do it all again. Eventually, you would be able to read the entire genome.
Now, after the fact, it sounds a fairly simple idea; indeed, Mullis says he still doesn’t understand