Scientists have produced cells with synthetic DNA. Can biology now establish the nature of life?
© iLexx - iStockphoto.comThe list of ingredients is short. Lots of carbon, hydrogen and oxygen, a generous helping of nitrogen, some phosphate and a little sulphur. Finally salts, a pinch of cobalt, zinc and manganese. One could fertilise fields with it. Or create life. The precise mixture that transformed elements of dead matter into living nature has been lost for four billion years. Back then, it was clearly a hit. Soon after the first, primitive life forms came into being, Earth was teeming: bacteria, protozoa, fungi, plants and then finally animals appeared - life was a recipe for success.
Matter created in test tubes and machines comes to life for the first timeTo date no-one has even come close to cataloguing the world's breathtaking biological diversity, let alone decoded its elementary force. Only one thing is certain: all living things on Earth are descended from a proto life form from the early period of the planet. But what was the spark made of that set off the fireworks of organic nature - and keeps life going to this day? »At what point does the decisive transition from dead to living matter occur?«, wonders chemist Helmut Schwarz of Berlin's Humboldt University, one of the best in his field. »To this day we don't know.«
Of all the biological sciences, it is the youngest discipline that is stepping up to provide an answer: synthetic biology aims to specifically alter life forms, control their inner processes, even create new creatures. Together with genome research it is penetrating ever deeper towards the core of life. How far it has already come became apparent last Friday, when visionary researcher Craig Venter presented his latest coup in the academic journal Science. In the laboratories of his private J. Craig Venter Institute (JCVI) in Rockville, Maryland, scientists have created a micro-organism that is entirely controlled by artificially synthesised DNA - which was created in machines from dead atoms. And this creature is growing and multiplying: »My God - it lives«, shuddered the Frankfurter Rundschau newspaper.
In 1998, Venter attracted worldwide attention with the start of his legendary race against the international project to decipher the human genome. The newspapers celebrated him as a genomics guru. The furore was no smaller when he promised to create life. Artificially programmed cells, explained Venter, could make the principles of life apparent while ridding the world of energy problems, producing medicines or purifying polluted ground along the way.
His team, which includes some of the brightest minds in technology and theory, has meanwhile carried out four spectacular experiments:
- The scientists perfected the process of genome transplants. For the first time, they succeeded in transferring the complete genetic information of one type of bacteria to another.
- In 2006 they removed all unnecessary ballast from the genes of the Mycoplasma genitalium germ and defined the genetic minimum without which a cell cannot exist, an essential code of less than 400 genes.
- In 2008 they succeeded in transforming digitalised genetic information back into bio matter. By means of database codes the researchers reconstructed bacterial DNA piece by piece.
- In a fourth and decisive step, Venter's team has now brought synthetic DNA to life. Transferred into the cell capsule of a different type of bacteria, the artificial molecule took control of its life functions. Under its command the foreign microbes were transformed into members of the species from which the template for the synthetic DNA transplant had come.
The converted organism, explains Venter with no hint of modesty, is »the first self-replicating species whose parents are a computer file«. No promethean spark as in Mary Shelley's literary original was required to awaken the Frankencell in Maryland; its vital essence is information, encoded in the letter sequence of the artificial molecule bearing the cryptic name JCVI-syn1.0. Now at the very latest Rudolf Virchow's belief that every cell is created from a cell (»omnis cellula e cellula«) seems outdated. Venter's creation was not made out of thin air, however. His team required almost intact cells for the experiment. But laboratories worldwide are working on artificially manufacturing all other necessary components of life. Life goes on, could be read in exclusive scientists' online forum Edge, »but it will never be the same again«.
Is life a fundamental property of matter?For Venter it is a creative triumph. But his Faustian desire for knowledge has always made ethicists, theologians and politicians uncomfortable, and even more so bio scientists themselves. For some of them, »Darth Venter« is in league with the dark side of the force. »Celera - speed matters«, was the motto he issued for his company when he took on the state-run human genome consortium he had criticised as petty and plodding. He has not forgotten the scorn he received for it, and demonstrates an Old Testament thirst for revenge at every opportunity. This time by poking around in the biological community's greatest wound in front of the whole world. His success, he announced, was not merely technological progress, but also a philosophical breakthrough. Following his pioneering achievement, biology could finally address its core problem.
The life sciences do indeed find themselves faced with an uncomfortable truth. The discipline of biology - derived after all from the Greek bios (life) and logos (teaching) - has never succeeded in providing a universal explanation of life. Metabolism, growth, reproduction: the textbooks barely go beyond a phenomenological definition of life. »Biology has no theory«, says science historian Ernst-Peter Fischer. At least the idea of a vis vitalis, an immaterial life force that inhabits all organic matter - a notion that occupies esoterically minded people to this day - finally seems to have been laid to rest.
But do scientific theories really explain the creation of life any better? Random chemical reactions gradually created biological molecules in the primordial soup of the early oceans, so the standard opinion; among these molecules, the first signs of life appeared - primitive metabolic processes, protein-like compounds and short nucleic acids, the predecessors of DNA. From the molecules of the primordial soup to the formidable architectures of biologically active atomic unions, from the first cell to human beings, it all seems to have been a chain of coincidences, accidents and incidents in which the complexity of what existed increased until what was formed brought forth new characteristics. What if life were a fundamental property of matter, an inevitable result of the laws of nature, as the Belgian biochemist and Nobel Prize laureate Christian de Duve has postulated? If this spark of life was created with the Big Bang, the universe should be brimming with aliens. Currently, biologists are struggling to fully comprehend all the life processes of a cell, its interactions with the overall organism and with its environment. But is that even possible? And if so, can these data be pieced together into a simulation of life, as imagined for example by US biologist Leroy Hood? According to Hood, life can be understood like a radio: by first examining its individual parts and then finding out how they work together.
Researchers are hoping for an epochal epiphanyHood is one of the most brilliant minds in the biological sciences, at the forefront of the new discipline of systems biology. The revolution in genome research has not only dramatically changed working in biology, he explained in late 2008 at a conference in Heidelberg, »it will overturn our understanding of biology«. And indeed the inkling of an epochal epiphany can be felt on the research scene, as if an Einstein of biology were on the way to opening up new dimensions for research and philosophy through a theory of relativity of life. Such a figure has existed only once so far in the history of biology. With Charles Darwin began a gigantic revolution - his insight was the first important inroad of analytic thinking into a discipline that had until then been solely descriptive. But the theory of evolution only explains the diversity of life, not life itself.
Even before Venter's experiments, theorists had formulated a radically new view of the mystery. »Life«, says Leroy Hood, »is information.« Similarly to Darwin on his expeditions into nature, today's researchers are seeking the solution to the riddle of life in DNA. As Darwin collected and compared animals and plants, so they are looking for central patterns in examining the genetic information of life forms. The DNA of 1,000 humans is currently being decoded; soon the genetic data of 10,000 vertebrates are to follow. With the results of these and other projects, the evolution of the code of life could be reconstructed even far back into the prehistory of the planet. This decoding is delivering gigantic amounts of data - and causing biology to undergo the next transformation: it is becoming an information science. Only special algorithms on mainframe computers can cope with the flood of data, and seem to repeatedly confirm the irritating discovery that life is indeed information - and nothing else.
Venter's information transplant experiment also appears to confirm this theory. But what does it mean? Which as yet undiscovered law is hidden in the masses of data the sequencers are spitting out? The answer to this question would give human beings comprehensive power of creation: what is possible would, as Venter says, »only be limited by our imagination«. It's a paradox. While the databases are growing exponentially, although exciting new tools are within reach, the most important thing is lacking - a concept of the research subject itself. There are currently lamentable comprehension gaps in biology, said geneticist Leonid Kruglyak of Princeton University recently in scientific journal Nature: imagine if physicists had built the LHC particle accelerator in Geneva without knowing the laws of quantum mechanics and the theory of relativity.
»They would see all these elementary particles in their detectors but have no idea what to make of them. The responses of the measuring devices would be caused by processes that they did not understand in the slightest.« The feeling of having arrived at a dead end is driving researchers to despair. »We fooled ourselves into thinking that the genome was a transparent blueprint of life«, laments cell biologist Mel Greaves of the British Institute of Cancer Research. »But it isn't.« Meanwhile the genome appears more like a wafting continuum than a linear book. It contains not only the blueprints of proteins. The source code of life has many command hierarchies, is full of ever changing control sets. An ordering principle has so far not emerged. The cellular mechanics that carry out the commands also appear to be unexpectedly complex. Proteins, signal and messenger substances - even the communication systems of a cell seem interwoven like an impenetrable network.
The further the researchers advance into the heart of what is organic, the more levels of complexity open up. »It's as if we were climbing a mountain that keeps growing«, says biologist Jennifer Doudna of the University of California in Berkeley. »The more we know, the more we realise what we don't understand.« Is it reasonable to expect that we will someday understand everything in this expanding universe of life? Craig Venter may harbour fantasies of creation, but he has not made them come true. Arguments are therefore rife among experts as to how much artificial life Venter's group of researchers has actually created. The truly new creation of a creature that has never before existed on Earth is still far beyond the technical possibilities of the laboratory. So far, what Venter and his team have delivered is more akin to a copy of something that nature invented.
Craig Venter may harbour fantasies of creation, but he has not by far made them come true.Venter has not invented new life, declares Nobel Prize laureate David Baltimore, »he has imitated it«. For now, Homo Faber remains no more than a Homo Plagiarist, and life is still a mystery.
From DIE ZEIT :: 27.05.2010
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