Magyar Tudomány, 2009/7
On 15 April, 2009, Tibor Gánti chemical engineer, DcS. of biology, after a long period of illness, died. He was a titular Professor of the Eötvös Lóránd University, an exceptional researcher of the essence of life, the mental father of system chemistry. His ashes, corresponding to his own wish, were spread into the Danube at Zebegény. I am convinced that after several decades – if not his life- his life work will be considered victorious. I would like to sketch up in broad lines this life work.
Tibor Gánti had been a naturalist from his early years: he had been interested in everything: from living beings to cave searching. But he started to think about the essence of life already in his youth, as well. He was convinced that the question can be solved logically on the basis of chemistry, this is why he choose chemistry as his profession. Later on, he also noticed that also historically chemistry is the source, and he became the best-known researcher of the origin of life.
In microbiology, he made best use of his knowledge as the leader of the Laboratory for Yeasts of the Yeast Fabric (1958-1965), then he worked in the Fabric for Fine Chemicals of REANAL as chief engineer (1965-1974). At that time he elaborated and patented numerous industrial production procedures fitting today into the technological line of „artificial metabolism”. In his dissertation („Industrial syntheses by directed operation of reaction networks”) he summarised these activities, which is, at the same time, one of the citation points of his theoretical research. In the short periods between his industrial activities he visited libraries, following thus the results of the developments in molecular biology. His orientation capability was improved by his earlier work in the field of X-ray cristallography. His interest in this problem was published in his first book on this subject „Revolution in the research of life”, Gondolat, 1966), which, filling up a gap, has become a text-book at the Medical University for years. Its last chapter (Life and Death) made an advance to his future work on basic theoretical biology. After that, he lectured on biochemistry to students of biology at the Eötvös Lóránd University (1968-1972).
In the meantime, he works at his large opus „The principle of life” (Budapest, Gondolat, 1971), appearing as an educational book simply because the author does not see any other possibility as realistic. The first part of the book (New data) summarises in an up-to-date way molecular biology (it may be considered a revised version of his earlier book), whereas the second part expresses the bases for what is known today as the chemoton theory, and which is known now world-wide as the chemoton theory. With a striking intellectual bravity, he insists that the enzymes do not play a decisive role in the minimum organization of life. This concept – in the light of the educational activities of Gánti in the field of molecular biology – is very amazing. His recognition consists in the hypothesis that the basic unit of life should be very simple, whereas the known enzymes are obviously the result of a long evolution process. In other words, though the enzymes accelerate, regulate certain processes, but we have to ask also what the nature of regulated systems is!
Already in his book entitled „The revolution in the research of life” it has been said that life has two different kinds of process units: one of them drives living systems to one direction (as is the case in the steps of cell cycles or, more generally, as is manifested in ontogenesis, this is called in Gánti’s work of 1966 as main cycle), and the other one is connected to metabolism and with a stability in spite of the continuous change (homeostasis). This thought is expressed in the first edition of the Principles of Life in the language of abstract chemistry: the main cycle is an idealised template replication, while metabolism is a cycle in which the system produces the matter needed for the system started from the starting materials. An outstandingly important feature of both subsystems is autocatalysis, that is they are the catalysts for their own production. This has been obvious in template reproduction even then, but the majority of researchers would not consider metabolim autocatalytic. Gánti returned year by year to this subject, and indicated that e.g. the Calvin cycle or the reductive citric acid cycle are autocatalytic at the level of small molecules (while elementary reactions are catalysed by enzymes). One of the cornerstones of chemoton theory is the self-reproducing „chemical engine”.
It may be noticed that the chemoton model thus defined does not contain any spacial limiting element (membrane). Originally Gánti thought that the membrane function is in its importance secondary, so as paper is secondary to meat. Later on, Dénes Domján convinced him to give up this concept, but to this, another development was needed: the model of liquid mosaics for biomembranes was only published in 1972 by S. Jonathan Singer and Garth L. Nicholson. From this, it became obvious for Gánti that he had to complement his original model with a third autocatalytic subsystem, with the idealised model of a membrane. Since 1974, the chemoton has been considered a system consisting of three subsystems. The chemoton theory searches for the basic chemical element of life, and its basic explanation is a logical one. It is another question that Gánti emphasised from the beginning that it means a mental stepping-stone for understanding the origin of life in searching for chemical evolutionary ways leading to the spontaneous appearance of chemoton-like systems. According to him, the information appearing in the sequence of macromolecules has been utilised only in a later period of evolution, though nucleic acids formed already earlier parts of the system.
It turned out only nowadays how deep this recognition is. We performed bioinformatical studies on microorganisms with almost fully known metabolism networks. It is true for all of them, without any exceptions, that their metabolism can be started only in the presence of all the genes, enzymes and nutrients. To this, one has to ensure also the autocatalytic nucleus (and this is also true for heterotrophic organisms).
This was the status of the theory in the first years of the seventies, when Gánti summarised the results of his theoretical research for the series Studia Biologica of the Akadémiai Kiadó (Budapest). The manuscript was let drag on for more than a half decade, until it appeared finally in 1979 (at the same time, it appaered also at the University Park Press, Baltimore).
We may say that the work of Gánti has been recieved in Hungary mainly with disinterest, obtuseness, mockery and malice (from among which perhaps obtuseness has been the most tolerable). Not only that theoretical biology has not been accepted at that time, but it has also been stupefying that enzymes have been left out of the model. The majority of scientists did not agree with his idea that models should be analysed in an exact way. However, Gánti brought about also in this field a starting innovation: he discovered cycle stoichiometry. The basic idea of this is very simple: catalysts (and thus also enzymes) fall out of usual chemical reactions, since they are reformed in the reaction. This fault has been thought to be eliminated qualitatively, if above the arrow of the reaction the name of catalyst has been written. However, this does not contain any quantitative information, it does not turn out how much enzyme is capable of transforming how much substrate. If , however, one mole of the enzyme transforms one mole of the substrate, it is then univocal, but we need further also the number of turn-arounds performed. Based on this train of thoughts, the stoichiometric characterisation of autocatalytic cycles became possible.
The theory has not come out better abroad, the formulation is perhaps more striking if we say the professionals could not understand its essence. Theoretcal biologists, with the exception of a very few, dealt with evolution and ecology, but not with the organisational modes of chemical processes to produce life. As we will see, in later years the situation changed radically, what, however, does not help any more the scientist, who died, but does help science.
In spite of obtuseness, work has been continued. In 1978, the second edition of „The principle of life” appeared, with a ripened structure and content. And this was the time when enzymes obtained a role in the theory, though in a quite unusual form. Gánti turns back to the idea of Carl Woese, Francis Crick and Leslie Orgel at the end of the sixties, and he indicated the direction of evolution of templates reproduced in chemotons in their direct enzymatic function. In other words, since then, enzymatic RNA’s (we call them now riboenzymes) have got a significant role in the theory. Actually, in two publications of Gánti (1979 and 1983) the „RNA –world” is fully present, though the article by Walter Gilbert characterised as „unflurling the flag” appeared only in 1986.
Gánti made his D.Sc. degree in 1980. The defence of his theses was an experience for the people taking part at it, also in the negative sense, due to the obstinate attack by Tamás Keleti. Though he backed down to some extent at the open and at the closed meetings, he gave zero point to the dissertation. However, the dissertation passed through even so, and Gánti became soon titular Professor at the Department of Genetics and at the Department of Plant-taxonomy and Ecology of the Eötvös Lóránd University (until 1999), where we learnt theoretical biology lectured by him. At the University, Professor Gábor Vida and Professor Tibor Simon supported his educating and research work. His status was professional advisor of the Ecology Modelling Team of the Hungarian Academy of Sciences.
Although he attracted numerous talented young people ( I dare say that this was also a reason for him not being too popular), he could not keep them; he was not flexible enough to this. As Károly Simonyi writes about a scientist in his work „The cultural history of physics”, „he was a captive of his own theory”, and he judged everything and everybody from this point of view. He was not an expert in packing his say for different utilisations, as he told himself: „I am good in strategy, but bad in tactics”. This key sentence explains a lot about his difficulties in publication, as well. „He never learnt to write an article” said someone about him, but this statement should be interpreted correctly. The articles by Gánti are very clear, only they cannot sell the concept to a part of the mistrustful readers.
In the eighties, he dealt mainly with two themes. He wrote his two-volumed monograph entitled „The Chemoton Theory I-II” edited by OMIKK in 1984 and 1989). He was the Chief Editor of the journal „The World of Nature”, and in many respects he reformed the journal.
In the nineties it seemed that the theory died, practically nobody dealt with it. At that time Gánti founded his enterprise „Cogitator” which dealt with studies and reports on environment protection with the cooperation of botanists, zoologists and ecologists.
In 1995, by the author of this necrolog and John Maynard Smith a work entitled „The big steps of evolution” appeared, in which we tried to fit Gánti’s work to the place due to him. We have done similarly in our parallel article in Nature. From this time on the seemingly dead theory started to show life signs again. Around 2000, several scientists, among them we, suggested to the Oxford University Press to publish the works of Gánti, which - at the usual closed meeting - was accepted by the senate of the publisher. The volume contains the edited versions of two earlier books, a further study by the author and studies evaluating the works from philosophical and biological point of views (by James Griesemer, professor of philosphy at University of California and Eörs Szathmáry). Almost simultaneously, the serial editor Pál Mezey offered to let the two-volume monograph appear in the series Kluwer Mathematical and Computational Chemistry. Preparation works were carried out in Collegium Budapest, where Tibor Gánti was fellow for a year. Both big books appeared in 2003.
In the last 5 years Gánti acted as a „home worker” of Nagymaros for the astrobiological group of the Collegium Budapest supported by the Hungarian Space Research Office and the European Space Agency. The idea is that for several months in every year, life conditions may be present in the dark dune spots on Mars suitable for even simple, photosynthesizing living beings near to the surface: Time will decide whether there is really life in these spots.
As I indicated earlier, the world has changed a lot. To European initiation, last year the science of system chemistry was born dealing with the analysis and synthesis of autocatalytic chemical systems. The COST project organising the in statu nascendi branch of science had a very high point value in the competition of applications, its second conference will take place at Balatonfüred in this October. The president of the initiative, Professor Günther von Kiedrowski (Bochum, Germany) honours Tibor Gánti among the few founding fathers. Parallel to this, publications following his mental direction are appearing more often and often (several of them are cited in the References).
The partial pathology of science in our most recent times is shown also by the fact that the references do not keep pace with the intellectual influence acknowledged orally. The reason for this is simply that our today’s application and publication system compels people to show themselves original, even when they are not or not so much original. This behaviour undermines the old, noble traditions of professional citations (people refer to their personal friends or to those dangerous criticism may come from, the other references do not count).
In summary we may say that the intellectual sowing of Gánti starts to turn productive, but the deserved recognition keeps us still waiting. For Gánti it is now just the same, but it is not for Hungarian science. It is better late, than never. If I guess well, time will come when the chemoton theory will be valued as a very significant result of Hungarian science. Gánti would be worthy to the (made up) title of magister vitae due to his interest and activities. As a master of life, he searched for its basis, with an unprecedented persistance and a very modest support. For sure, he was not an artist of life, luck also kept away from him. But we usually forget the artists of life, but remember long the masters of life with honour.
Eörs Szathmáry - Corresponding fellow of the Hungarian Academy of Sciences