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Adleman-ScAm94 - Computing with DNA The manipulation of DNA...

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C omputer. The word conjures up images of keyboards and monitors. Terms like “ROM,” “RAM,” “gigabyte” and “megahertz” come to mind. We have grown accus- tomed to the idea that computation takes place using electronic compo- nents on a silicon substrate. But must it be this way? The comput- er that you are using to read these words bears little resemblance to a PC. Perhaps our view of computation is too limited. What if computers were ubiq- uitous and could be found in many forms? Could a liquid computer exist in which interacting molecules perform computations? The answer is yes. This is the story of the DNA computer. Rediscovering Biology M y involvement in this story began in 1993, when I walked into a molecular biology lab for the first time. Although I am a mathematician and computer scientist, I had done a bit of AIDS research, which I believed and still believe to be of importance [see “Bal- anced Immunity,” by John Rennie; Sci- entific American, May 1993]. Unfor- tunately, I had been remarkably unsuc- cessful in communicating my ideas to the AIDS research community. So, in an effort to become a more persuasive ad- vocate, I decided to acquire a deeper understanding of the biology of HIV. Hence, the molecular biology lab. There, under the guidance of Nickolas Chelya- pov (now chief scientist in my own lab- oratory), I began to learn the methods of modern biology. I was fascinated. With my own hands, I was creating DNA that did not exist in nature. And I was introducing it into bacteria, where it acted as a blueprint for producing proteins that would change the very nature of the organism. During this period of intense learn- ing, I began reading the classic text The Molecular Biology of the Gene, co-au- thored by James D. Watson of Watson- Crick fame. My concept of biology was being dramatically transformed. Biolo- gy was no longer the science of things that smelled funny in refrigerators (my view from undergraduate days in the 1960s at the University of California at Berkeley). The field was undergoing a revolution and was rapidly acquiring the depth and power previously associ- ated exclusively with the physical sci- ences. Biology was now the study of in- formation stored in DNA strings of four letters: A, T, G and C for the bases adenine, thymine, guanine and cyto- sine and of the transformations that information undergoes in the cell. There was mathematics here! Late one evening, while lying in bed reading Watson’s text, I came to a de- scription of DNA polymerase. This is the king of enzymes the maker of life. Under appropriate conditions, given a strand of DNA, DNA polymerase pro- duces a second “Watson-Crick” com- plementary strand, in which every C is replaced by a G, every G by a C, every A by a T and every T by an A . For ex- ample, given a molecule with the se- quence CATGTC, DNA polymerase will produce a new molecule with the sequence GTACAG. The polymerase enables DNA to reproduce, which in turn allows cells to reproduce and ulti- mately allows you to reproduce. For a
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