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“Man Is A Giant Lego Building Set“

“Man Is A Giant Lego Building Set“

Photo: A child watches out of a Lego house Mr. Fussenegger, you build microorganisms as you need them. How do you do that?

Martin Fussenegger: We work mostly with mammal cell and also with human cells which we genetically alter. By now we understand many individual genes of the human organism, whose characteristics can be defined. They are just like many little building blocks with specific functions. Synthetic Biology applies this knowledge of genetics: Just like with Lego building blocks, you can piece these individual genes together and combine them. What happens with these man-made pieced-together genes?

Fussenegger: The newly combined genes are built into a human cell. There they are attached to the internal cell networks. So the cell receives an additional function that it did not have before. It is then enwrapped with polymer plastic and sort of gets a type of plastic cover slipped over it. This is how the genetically altered cell turns into an implant. What is the purpose of this wrap?

Fussenegger: First, it makes sure the body’s own immune system does not perceive the implant as a foreign cell. This way an immune reaction is prevented. Second, it keeps the genes in the man-made cell from merging with the body’s own genes. The mesh of the plastic cover is semi-permeable, meaning it is tight enough so bigger matter like anti-bodies and genes cannot get through, though smaller matters like nutrients can. Even if a gene is known, it often has numerous functions, that on the other hand are not all known. Do you often get a surprise when you piece a gene together and something different happens than what you expected?

Fussenegger: We only use genes that are well researched and characterized, so we can be quite exact in predicting what is going to happen. Even though we are not immune to surprises, we experience relatively few during tests.

A molecular crutch as the universal answer? With the help of Synthetic Biology, you have created an implant that is targeted to help gout. Exactly how does it keep gout under control?

Photo: A cpw watches over the back of another one
Not only in the laboratory, but also in breedings man influences genes; © SXC

Fussenegger: For this you need to understand the cause of goat: Due to a fatty diet, people have more and more uric acid in their bodies. You get sick, if the uric acid level exceeds a certain level. There are a few drugs for gout, but they lower the uric acid levels down to zero, which is actually not good because uric acid catches free radicals that harm the body. Humans always need a steady uric acid concentration that should not be too high and not be too low. We used three building blocks for this implant. An uric acid transporter that moves the uric acid from the body into the cell, a uric acid sensor that measures the uric acid levels and –if needed- activates our third building block, an uric acid reducing enzyme. When uric acid levels are too high, the transporter delivers a lot of uric acid into the cell, the sensor activates the enzyme and it breaks down the uric acid. If there is too little uric acid in the cell, nothing happens, so it never falls below a certain minimum. This implant has already been successfully tested in mice and can now enter into the clinical phase. Are there also other medical developments in the field of Synthetic Biology that have reached this point?

Fussenegger: The business magazine that published the study, assured me that they have high interest in this publication, since this is the first time the metabolism was influenced in such a complex way by using this method. Based on today’s stage of development, which are the most promising uses for Synthetic Biology?

Fussenegger: If you abstract the system we developed for gout: it can be used for a lot of things. Apart from infectious diseases, I cannot think of any other disease where too much or too little of a certain matter and defective control systems are not the cause. With diabetes it is insulin, with cancer the amount of a certain protein is elevated. Our mechanism could become a general system for influencing molecular activities and thus cure diseases. Is this your personal vision as a researcher?

Fussenegger: Yes and that in this way we can get away from drugs some day and are able to treat preventatively. Today we only administer drugs after the disease has broken out. And to date we go by this rule: If it does not have any side effects, it does not have any effects at all. Molecular replacements such as our gout implant – by this I mean man-made aids that regulate defects on a molecular level – can open new doors. You do not wait until the disease is here, but you introduce such an implant into high risk patients at the front end – and thus you can prevent the disease from breaking out. The patient does not have to worry about drug dosage or side effects any more, because the molecular crutch regulates everything on its own and works in tune with the body. There are people who view the field of Synthetic Biology very critically due to ethical and safety reasons. After all, artificial life is being created here. How do you respond to such concerns?

Fussenegger: Both charges are hard for me to understand. Man never created anything that is truly new. He looks around the world, sees something and puts it together, but he did not invent the basic material, in this case bacteria and genes. In essence, man has always lived on this Earth like as if it was a giant Lego building set. At the same time, man is one himself. Is he allowed to build anything he can?

Fussenegger: I do not see an ethical or security issue in this case. The same procedures that are used in Synthetic Biology, meaning putting genes together in a new way and creating a different life by doing so, have been done for centuries with every hybridation and breeding controlled by man. We have been eating the meat of livestock that has been purposely bred to be fatter. And if somebody crosses a donkey and a horse and thereby created a new genetically altered being called a mule, nobody breaks into a panic either.

This interview was conducted by Anke Barth and translated by Elena O’Meara


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