The Pioneer of Genetic Engineering

History – research ––– 82 History – research ––– 83 year research stay at the University scientists had observed that many of Southern California in Los Angeles. strains of bacteria could defend After returning to Geneva, Werner themselves against attacking phages Arber devoted himself fully to and released only a small number Text: bacteria and viruses. He explained of phage progeny (or offspring). The The pioneer of Anke Fossgreen the reason for this decision at a astonishing thing was that although party held in his honor in 1978: “As these progeny grew vigorously in the a microbiologist, I’m convinced that event of a renewed infection, they no many fundamental questions of longer grew on their previous host genetic engineering biology can be explored by studying strain. Werner Arber, who was by very simple systems.” then the head of a research group, wanted to know how the bacteria Werner Arber studied the genetic held out against the phages. He makeup of intestinal bacteria suspected the existence of enzymes (Escherichia coli) and their patho- that could act as molecular scissors gens – viruses known as “phages” to selectively identify and break down that infect bacteria. In the past, other invading foreign DNA. After commencing his doctoral dis- ences at ETH Zurich and developed a sertation at the University of Geneva fascination with this mysterious mol- in 1953, Werner Arber presented a ecule. Indeed, he devoted his entire new publication at his weekly sem- research career to it. Thanks to a inar. In this article, the researchers groundbreaking discovery, Werner James Watson and Francis Crick de- Arber became one of the founding scribed the structure of DNA, a mol- fathers of genetic engineering, for ecule that served to encode genetic which he received the Nobel Prize information and that was wound into in Physiology or Medicine in 1978. the shape of a double helix. The ambitious scientist had Raised in a farming family in Gräni- acquired the necessary skills for chen in the Canton of Aargau, Werner genetic studies during his doctoral Arber went on to study natural sci- dissertation and as part of a one- History – research ––– 84 History – research ––– 85 Over the next few years, it slowly became clear just how revolutionary this actually was. After all, Werner Arber and his colleagues had discovered tools that could selectively cut up the threadlike DNA molecule – When Werner Arber received his No- even in a test tube. From then on, bel Prize at a ceremony in Stockholm researchers could insert individual in 1978, he was accompanied by DNA segments into other DNA mol- his family – specifically by his wife, ecules. The field of genetic engineer- Antonia, and his two daughters, He and his team did in fact discov- ing was born. Silvia and Caroline. Silvia Arber was er molecular scissors of this kind, ten years old when she gave a vivid which are known as restriction Today, researchers have access description of her father’s research, enzymes. The group also located to over 1,000 restriction enzymes, comparing the bacterial colonies to the short sections on the DNA chain which can be used at various loca- cities and the DNA to the king who where restriction enzymes identi- tions in the genetic makeup. In the ruled over them. Servants ensured fied attacking DNA as foreign. In early years, these enzymes had to that no foreign kings could enter the addition, the scientists answered a undergo a laborious cleaning process bacteria, and it was these servants second question – namely, how did in the lab, and researchers would – the scissors – that her father had the bacteria protect their own DNA exchange precious droplets of them discovered. from being attacked by the scissors? with other researchers. For some They had noticed that the bacterial time now, however, the enzymes Silvia Arber is now a neurobiologist DNA featured characteristic chemical have been available for scientists and leads a group of her own at the changes known as methyl groups, simply to order from a catalog for Biozentrum, as well as carrying out and it was these chemical appendag- use in their own laboratories. These research at the Friedrich Miescher es that prevented the scissors from tools allow researchers to cut genes Institute for Biomedical Research acting at that location. out of one organism and insert them in Basel. She and her sister Caro- into another in order to genetically line, who is also a professor, in her In other words, the bacteria had a modify bacteria, plants or animals. case at the University of Lausanne, sort of primitive immune system with continue to provide a regular supply which they protected themselves The toolbox available for genetic of scientific publications to feed against foreign DNA. This defense engineering has now acquired new their father’s insatiable appetite for system not only worked against types of gene scissors, the most research. DNA from phages produced in other powerful of which is known as host cells but also against the DNA Crispr/Cas. This enzyme was identi- of other bacterial strains in general. fied by the researchers Emmanuelle This was an astonishing finding with Charpentier and Jennifer Doudna huge implications for basic research. some 40 years after Werner Arber’s discovery as the pair sought to clari- fy another mechanism in the bacterial “immune system.” Crispr/Cas has conquered the world’s laboratories over the last few years and has entered practical use. In recognition of their discovery, Charpentier and Doudna received the 2020 Nobel Prize in Chemistry. History – research ––– 86 The tale of the king and his servants My father has discovered a servant who serves as a pair of scissors. If a foreign king invades a bacterium, this “I was only ten years old when my father received the Nobel Prize in servant can cut him into small frag- Physiology or Medicine in 1978. He ments, but he does not do any harm explained to me at the time what to his own king. it was and what his research was about, but I obviously had no idea what it all meant, and so I recorded Clever people use the servant with his story in my own words. Having the scissors to fi nd out the secrets of received piles of mail congratulating the kings. To do so, they collect many him, my father used the story in his servants with scissors and put them thank-you letters – and so the tale made its way all around the world. onto a king, so that the king is cut It was printed in newspapers, and into pieces. With the resulting little I also read it out on a Swiss radio pieces it is much easier to investigate program as a child. While I was in When I come to the laboratory of my father, I usually see some the secrets. For this reason my father Stockholm with him, the Queen plates lying on the tables. These plates contain colonies of bacteria. and King of Sweden even told me received the Nobel Prize for the discov- These colonies remind me of a city with many inhabitants. In each they were glad to have read the ery of the servant with the scissors. bacterium there is a king. He is very long, but skinny. The king has story – as otherwise they wouldn’t have understood what my father’s many servants. These are thick and short, almost like balls. My fa- research was actually about.” ther calls the king DNA, and the servants enzymes. The king is like – Prof. Silvia Arber a book, in which everything is noted on the work to be done by the servants. For us human beings these instructions of the king are a mystery..

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