at the museum and interviewed each staff member in turn in a small room, asking them what they had been doing with me and Rosti. That I had published my first results in East Germany and had prominently referred to that publication in the Nature paper—none of this impressed the Stasi. Instead, they impressed upon the museum employees that, as they put it, Uppsala University is a well-known antisocialist propaganda center. No matter how ridiculous this characterization of the oldest university in Sweden was, no East German citizens in their right mind would of course have anything to do with us after being told this by the Stasi.
I was depressed by the futility of dealing with a totalitarian system. Having entertained visions that our two competing political systems might grow closer, perhaps catalyzed by scientific contacts, I had hoped that I might contribute to the process in some small way. Little did I know the role that East Germany would play in my life, but at that point neither samples nor cooperation seemed to be in the cards.
In Zurich, I set about extracting DNA both from the small mummy samples I had left in my possession and from specimens of the marsupial wolf. Despite my enthusiasm for the PCR, getting it to work following Kary Mullis’s protocol was no picnic. It involved heating the DNA in a 98°C water bath to separate the strands, then cooling it in a 55°C water bath to let the synthetic primers attach to their targets, then adding the heat-sensitive enzyme and incubating the mix in a 37°C water bath to try and coax it to make the new strands. For each experiment, this tedious cycle of manipulations needed to be done at least thirty times. I spent hours on end in front of steaming water baths wasting many test tubes of expensive enzyme in my attempts to amplify pieces of DNA. Sometimes I was able to generate a weak product from modern DNA, but I had no luck with the badly degraded DNA from the thylacine and the mummy samples. I did have some success in showing, by electron microscopy, that much of the mummy and thylacine DNA was in short pieces. Some DNA molecules had even become linked to each other by chemical reactions, a feature that was sure to make them intractable to multiplication either in bacteria or by PCR in the test tube. This was not surprising, given some findings I had made in 1985, when I had visited Tomas Lindahl’s lab in Hertfordshire outside London for a few weeks. Tomas is originally of Swedish descent and one of the world’s experts on chemical damage to DNA and the systems that organisms have evolved to repair it. In his lab I had shown that there was evidence for several forms of damage in the DNA I had extracted from the old tissues. These results as well as my new Zurich findings constituted solid descriptive science, but they did not take me closer to my goal of reading DNA sequences from long-extinct creatures. Months passed in front of the water baths—as well as on the Alpine ski slopes—but no breakthroughs transpired, so it was with a distinct sense of relief in the spring of 1987 that I left Zurich for Berkeley, where Allan Wilson was back in residence.
Upon arriving in the Biochemistry Department at UC Berkeley, I soon realized that I was in the right place at the right time. Kary Mullis had been a graduate student there before he moved to the Cetus Corporation, down by the Bay, where he invented the PCR. Several of Allan’s previous graduate students and postdocs worked at Cetus. The result was that while I had been alone in my struggle to get the PCR to work in Zurich, in Berkeley many people worked on it, and as a result many improvements were made. At Cetus, they had cloned and expressed a version of DNA polymerase, the enzyme used in the PCR to make new DNA strands, from a bacterium that grows at high temperatures. Since this enzyme could survive high temperatures, there was no need to open the test tubes and add enzyme during each PCR cycle. This meant
I was depressed by the futility of dealing with a totalitarian system. Having entertained visions that our two competing political systems might grow closer, perhaps catalyzed by scientific contacts, I had hoped that I might contribute to the process in some small way. Little did I know the role that East Germany would play in my life, but at that point neither samples nor cooperation seemed to be in the cards.
In Zurich, I set about extracting DNA both from the small mummy samples I had left in my possession and from specimens of the marsupial wolf. Despite my enthusiasm for the PCR, getting it to work following Kary Mullis’s protocol was no picnic. It involved heating the DNA in a 98°C water bath to separate the strands, then cooling it in a 55°C water bath to let the synthetic primers attach to their targets, then adding the heat-sensitive enzyme and incubating the mix in a 37°C water bath to try and coax it to make the new strands. For each experiment, this tedious cycle of manipulations needed to be done at least thirty times. I spent hours on end in front of steaming water baths wasting many test tubes of expensive enzyme in my attempts to amplify pieces of DNA. Sometimes I was able to generate a weak product from modern DNA, but I had no luck with the badly degraded DNA from the thylacine and the mummy samples. I did have some success in showing, by electron microscopy, that much of the mummy and thylacine DNA was in short pieces. Some DNA molecules had even become linked to each other by chemical reactions, a feature that was sure to make them intractable to multiplication either in bacteria or by PCR in the test tube. This was not surprising, given some findings I had made in 1985, when I had visited Tomas Lindahl’s lab in Hertfordshire outside London for a few weeks. Tomas is originally of Swedish descent and one of the world’s experts on chemical damage to DNA and the systems that organisms have evolved to repair it. In his lab I had shown that there was evidence for several forms of damage in the DNA I had extracted from the old tissues. These results as well as my new Zurich findings constituted solid descriptive science, but they did not take me closer to my goal of reading DNA sequences from long-extinct creatures. Months passed in front of the water baths—as well as on the Alpine ski slopes—but no breakthroughs transpired, so it was with a distinct sense of relief in the spring of 1987 that I left Zurich for Berkeley, where Allan Wilson was back in residence.
Upon arriving in the Biochemistry Department at UC Berkeley, I soon realized that I was in the right place at the right time. Kary Mullis had been a graduate student there before he moved to the Cetus Corporation, down by the Bay, where he invented the PCR. Several of Allan’s previous graduate students and postdocs worked at Cetus. The result was that while I had been alone in my struggle to get the PCR to work in Zurich, in Berkeley many people worked on it, and as a result many improvements were made. At Cetus, they had cloned and expressed a version of DNA polymerase, the enzyme used in the PCR to make new DNA strands, from a bacterium that grows at high temperatures. Since this enzyme could survive high temperatures, there was no need to open the test tubes and add enzyme during each PCR cycle. This meant
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