The Hungarian biologist Tibor Gánti is hardly known to anyone. But now, a decade after his death, his chemotonic model of the origin of life is finally going around the world.
When the biologist Tibor Gánti died on April 15, 2009, at the age of 75, he was anything but well known. He had spent much of his career behind the Iron Curtain that had divided Europe for decades and hindered the exchange of ideas.
If Gánti's theories had been better known during the communist era, he might today be hailed as one of the most innovative biologists of the 20th century.
His great achievement: He developed a model of the simplest possible living organism. He christened it chemoton, and it could provide an exciting explanation for the beginning of life on earth.
The origin of life is one of the most baffling puzzles in science - partly because it is actually several puzzles. What was the earth like when it came into being? What gases was the air made of? Which of the thousands of chemicals that living cells use today are essential - and when did these essential substances originate?
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Perhaps the most difficult question is also the simplest: What was the first organism?
For scientists trying to reconstruct this spark of life, the chemoton offers an attractive result for experiments. If you can get chemicals to assemble themselves into a chemotone, it shows a way in which life could have originated. Some research groups are already coming astonishingly close to this model.
And for astrobiologists interested in life beyond our planet, the chemotone offers a universal definition of life. And one that does not rely on specific chemicals such as DNA, but is based on an overarching organizational model.
“Gánti has thought more deeply about the basics of life than anyone I know,” says biologist Eörs Szathmáry from the Center for Ecological Research in Tihany, Hungary.
The beginning of life
There is no single scientific definition of life, although there has been no lack of experimentation: a 2012 paper identified 123 published definitions. It proved difficult to formulate a definition that encompasses all life but excludes everything inanimate with life-like properties, such as fire and cars. Many definitions say that living things can reproduce. But a rabbit, a human, or a whale cannot reproduce on its own.
In 1994 a NASA committee described life as "a self-sustaining chemical system capable of Darwinian evolution". The word “system” can describe a single organism, a population or an ecosystem. This avoids the problem of reproduction, but at a price: blurring.
What few people knew at the time was that Gánti had already shown another possibility two decades earlier.
Tibor Gánti was born in 1933 in the small town of Vác in the heart of Hungary. His childhood was already marked by political conflicts. Hungary supported Nazi-ruled Germany during World War II, but in 1945 the Hungarian army was defeated by the Soviet Union. The totalitarian regime dominated the regions around the border between Europe and Asia for decades and Hungary, like many Eastern European nations, became a satellite state.
Fascinated by the nature of living things, Gánti studied chemical engineering before becoming an industrial biochemist. In 1966 he published a book on molecular biology entitled "Forradalom az Élet Kutatásában" or "Revolution in Life Research", which was a popular textbook at universities for years - also because there were few others on the subject. The book asked whether science understands how life is organized and concluded that it doesn't.
In 1971 Gánti tackled the problem in a new book, "Az Élet Princípiuma" or "The Principles of Life". This book, published only in Hungarian, contained the first version of his chemoton model, which he considered the basic unit of life. This early model of the organism was incomplete, however, and it would be another three years before he published the final version - again in Hungarian only, in a paper that is not available online.
Wonder year of science
Worldwide, 1971 was something of a parade year for the exploration of the origin of life. In addition to Gánti's rather unknown work, the science presented two other important theoretical models.
The first comes from the American theoretical biologist Stuart Kauffman, who argued that living organisms must be able to copy themselves. In speculating how this might have worked before cells were created, he focused on different combinations of chemicals.
Imagine that chemical A triggers the formation of chemical B, which in turn triggers the formation of chemical C, and so on until one link in the chain creates a new version of chemical A. After a cycle, two copies of each group of chemicals exist. If there are enough raw materials, another cycle will produce four copies and so it goes on exponentially.
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Kauffman called such a group an "autocatalytic set" and argued that such groups of chemicals could have been the basis for first life. The sets became more and more complicated until they produced and used a number of complex molecules such as DNA.
The second idea comes from the German chemist Manfred Eigen. He described a "hypercycle" in which several autocatalytic sets combine into a single larger one. However, Eigen's variant had a crucial difference to Kauffman's model: in a hypercycle, some of the chemicals are genes and therefore consist of DNA or another nucleic acid, while others are proteins that are produced on the basis of the information in the genes. This system could evolve due to changes - i.e. mutations - in the genes, a function that was missing in Kauffman's model.
Gánti had come to a similar idea independently, but he developed it further. He argued that two key processes must take place in any living organism. First, he has to build and maintain his body; that is, he needs a metabolism. Second, it must have some kind of information store, such as a gene or genes, that can be copied and passed on to offspring.
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Gánti's first version of his model essentially consisted of two autocatalytic groups with different functions that merged to form a larger autocatalytic group. It wasn't that different from Eigen's hypercycle. The following year, however, a journalist pointed out a crucial flaw to Gánti: Gánti assumed that the two systems were based on chemicals floating in the water. But left to their own devices, they would drift apart - and the chemotone would "die".
The only solution was to add a third system: an outer barrier to contain it. In living cells, this barrier is a membrane made up of fat-like chemicals called lipids. The chemotone had to have such a barrier to hold itself together. Gánti concluded that it had to be autocatalytic too so that it could sustain itself and grow.
And so the end concept of the chemotone came about - Gánti's concept of the simplest possible living organism: genes, metabolism, and membrane, all interconnected. The metabolism produces building blocks for the genes and the membrane, and the genes influence the membrane. Together they form a self-replicating unit: a cell that is so simple that not only could it arise relatively easily on Earth, but could even explain alternative biochemistry in foreign worlds.
Gánti's forgotten model
"Gánti portrayed life really well," says synthetic biologist Nediljko Budisa from the University of Manitoba in Winnipeg, Canada. “It was a revelation to read.” Budisa didn't discover Gánti's work until 2005, however. Outside of Eastern Europe, it remained relatively unknown for decades and there were only a few English translations on the market.
The chemotone didn't become available to English speakers until 1987, in a paperback with a pretty rough translation, says James Griesemer of the University of California, Davis. Few took any notice. Szathmáry later gave the chemotone a place of honor in his 1995 book "The Major Transitions in Evolution", which he wrote with John Maynard Smith. This at least led to a new English translation of Gánti's 1971 book with additional material, which appeared in 2003. But the chemotone still remained a wallflower, and six years later Gánti was dead.
In a way, Gánti didn't exactly help his model to gain more prominence: He was considered a difficult colleague. Szathmáry says that Gánti was stubbornly fixated on his model and was paranoid, which made it "impossible to work with him".
But perhaps the biggest problem for the chemoton model was a trend that emerged in the last decades of the 20th century: Research sought to simplify the complexities of life in favor of increasingly minimalist approaches.
For example, one of the most prominent hypotheses that are still popular today is that life began with RNA alone.
Like its molecular relative, DNA, RNA can carry genetic information. But what is crucial is that RNA can also function as an enzyme and accelerate chemical reactions. This led many experts to the thesis that the first life did not need anything other than RNA in order to get going. This RNA world hypothesis, however, met resistance, largely because science has not found a species of RNA that can copy itself. Even RNA-driven viruses like the coronavirus need human cells to multiply.
Other researchers have argued that life began with lipids alone. Such ideas are far from Gánti's combined approach.
Who makes a real chemotone?
However, since the turn of the millennium, the trend in research has been going in the other direction again. Researchers are now more focused on the ways in which the chemicals in life work together and how these cooperative networks might have come about.
Since 2003, Jack Szostak of Harvard Medical School and his colleagues have been building increasingly lifelike protocells: simple versions of cells that contain a range of chemicals. These protocells can grow and divide, i.e. replicate themselves.
In 2013, Szostak and his student at the time, Kate Adamala, brought RNA to copy itself within a protocell. In addition, the genes and the membrane can be coupled: While the RNA inside multiplies, it exerts pressure on the outer membrane and allows the protocell to grow.
Szostak's research “is very reminiscent of Gánti,” says synthetic biologist Petra Schwille from the Max Planck Institute for Biochemistry in Martinsried, Bavaria. She also refers to the work of Taro Toyota at the University of Tokyo in Japan. He made lipids inside a protocell so that the protocell could form its own membrane.
One argument against the idea of chemotone as the first form of life was that it required so many chemical components, including nucleic acids, proteins, and lipids. Many experts thought it unlikely that these chemicals would all come from the same raw materials in the same place, hence the appeal of stripped-down ideas like the RNA world.
But recently, biochemists have found evidence that all of life's key chemicals can be made from the same simple raw materials. In a study published in September 2020, researchers led by Sara Szymkuć, at that time at the Polish Academy of Sciences in Warsaw, compiled a database of experiments from several decades that attempted to create the chemical building blocks of life. Szymkuć found that tens of thousands of critical components, including the basic building blocks of proteins and RNA, can be made from just six simple raw materials such as water and methane.
But none of these experiments have resulted in a functioning chemotone. This may simply be due to the fact that it is complicated, but Gánti's model may not be an exact representation of the first life on earth. Yet chemotone gives us a chance to speculate about how the individual components of life work together. And that is exactly what is increasingly driving today's approaches to understand the origins of life.
It is significant, says Szathmáry, that Gánti's works are now increasingly cited. While the specific details differ, the current approaches to the genesis of life are much closer to what he had in mind: a blended approach that doesn't focus on just one of the key systems of life.
"Life is not just proteins, life is not just RNA, life is not just lipid bilayers," says Griesemer. "What is it then? It is all of these things that are interconnected in the right organizational structure. "
Source: National Geographic
