Keep, Delete, Modify: Synthetic Genes, Synthetic Cells, Synthetic Life
Reporter: Aviva Lev-Ari, PhD, RN
Nature needed about one billion years to create the simplest single-cell organisms that swam around in the primordial soup. Now, scientists are eager to create synthetic life – but better and faster.
Hamilton Smith (Nobel Prize in Chemistry 1978 with Werner Arber and Daniel Nathans) started his lecture at the 64th Nobel Laureate Meeting in Lindau with a quote from Richard Feynman (Nobel Prize in Physics 1965): Feynman had probably meant physical models, whereas Smith referred to living organisms. In his laboratory at the J. Craig Venter Institute, he tries to create synthetic cells: “I hope that if we create that, we will understand.”
Nowadays, the entire human genome has been decoded. But how a live human being develops from DNA molecules, a human being that can breath, eat, walk, study, love, receive Nobel Prizes and award them – nobody really understands yet. Even for single-cell organisms, this isn’t crystal clear. Even the simplest bacteria exhibit genes without apparent function, that are not essential for life. During evolution, a lot of ‘genetic waste’ has accumulated that might have been useful at some point, but was rendered useless by mutations. Some genetic fragments were in fact smuggled into the genome by viruses, others were created by accidental duplications of genetic segments. Numerous molecular mechanisms lead to many genetic variations – rendering evolution possible in the first place. But over time, many of these genes and segments have become useless.
Currently Smith tries to tidy up the genome of Mycoplasma mycoides, a microbe normally living in the digestive tract of ruminants. Originally Smith and his team wanted to use the genome of Mycoplasma genitalium, the bacterium with the smallest known genome – it needs only 475 genes to live. Smith estimates that about 100 of these are non-essential. But since M. mycoides has a much higher cell division rate, although its genome is twice as large, experiments with M. mycoides proved to be more effective. During this ‘minimal cell project’, the researchers switch off one gene after another and study the effects on the microbes. (And the slower the microbes grow, the longer the researchers have to wait for their results.) Smith’s final goal is “a genome that is very understandable – we are searching for the genetic kernels of life”.
Smith also assumes that all genes from the last group can be switched off without negative impacts on the microbes. Concerning the middle category, the researchers have to carefully weigh all options. When all is done, the result should be a bacterium that can still multiply rapidly, at least in laboratory conditions that offer plenty of nourishment, constant temperatures, but no competitors. The researchers’ goal is a fifty percent genome reduction in a happily thriving microbe that divides at least once in 100 minutes.
Smith likes using computer terms to describe his work. He compares the genome of any organism with its software, the rest is hardware (the cytoplasm, proteins and enzymes), controlled by said software. As soon as a cell receives a new genetic program, it starts to put this program to use. In order to test their own synthetic programs, Smith and his team replaced the bacterium’s DNA with synthetic DNA containing their basic program. To date, the old ‘hardware’ has not adopted the new program ‘update’. In computer speak, troubleshooting and maintenance are called “debugging”: Smith and his team will be busy with debugging for some time.
Source: blog.lindau-nobel.org
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