Alfred Gierer

Biological evolution and technological innovation, while differing in many respects, also share common features. In particular, implementation of a new technology in the market is analogous to the spreading of a new genetic trait in a population. Technological innovation may occur either through the accumulation of quantitative changes, as in the development of the ocean clipper, or it may be initiated by a new combination of features or subsystems, as in the case of steamships. Other examples of the latter type are electric networks that combine the generation, distribution, and use of electricity, and containerized transportation that combines standardized containers, logistics, and ships. Biological evolution proceeds, phenotypically, in many small steps, but at the genetic level novel features may arise not only through the accumulation of many small, common mutational changes, but also when distinct, relatively rare genetic changes are followed by many further mutations. In particular, capabilities of biologically modern man may have been initiated, perhaps some 150 000 years ago, by one or few accidental but distinct combinations of modules and subroutines of gene regulation which are involved in the generation of the neural network in the cerebral cortex. It is even conceivable that it was one primary genetic event that initiated the evolution of biologically modern man, introducing some novel but subtle feature of connectivity into the cerebral cortex which allowed for meta-levels of abstraction and upgraded modes of information processing. This may have set the stage for the evolution of integrated but diverse higher capabilities such as structured language, symbolic thought, strategic thought, and cognition based empathy.

Validity of physical laws for any aspect of brain activity and strict correlation of mental to physical states of the brain do not imply, with logical necessity, that a complete algorithmic theory of the mind-body relation is possible. A limit of decodability may be imposed by the finite number of possible analytical operations which is rooted in the finiteness of the world. It is considered as a fundamental intrinsic limitation of the scientific approach comparable to quantum indeterminacy and the theorems of logical undecidability. An analysis of these limits, applied to dispositions of future behaviour, suggests that limits of decodability of the psycho-physic relation may actually exist with respect to brain states with self-referential aspects, as they are involved in mental processes. Limits for an algorithmic theory of the mind-body problem suggested by this study are formally similar to other intrinsic limits of the scientific method such as quantum indeterminacy and mathematical undecidability which are also related to self-referential operations. At the metatheoretical level, hard sciences, despite their reliability, universality and objectivity, depend on metatheoretical presuppositions which allow for multiple philosophical interpretations. -/- .

The introductory personal remarks refer to my motivations for choosing research projects, and for moving from physics to molecular biology and then to development, with Hydra as a model system. Historically, Trembley’s discovery of Hydra regeneration in 1744 was the begin¬ning of developmental biology as we understand it, with passionate debates about preformation versus de novo generation, mechanisms versus organisms. In fact, seemingly conflicting bottom-up and top-down concepts are both required in combination to understand development. In modern terms, this means analysing the molecules involved, as well as searching for physical principles underlying development within systems of molecules, cells and tissues. During the last decade, molecular biology has provided surprising and impressive evidence that the same types of mol¬ecules and molecular systems are involved in pattern formation in a wide range of organisms, including coelenterates like Hydra, and thus appear to have been “invented” early in evolution. Likewise, the features of certain systems, especially those of developmental regulation, are found in many different organisms. This includes the generation of spatial structures by the interplay of self-enhancing activation and “lateral” inhibitory effects of wider range, which is a main topic of my essay. Hydra regeneration is a particularly clear model for the formation of defined patterns within initially near-uniform tissues. In conclusion, this essay emphasizes the analysis of development in terms of physical laws, including the application of mathematics, and insists that Hydra was, and will continue to be, a rewarding model for understanding general features of embryogenesis and regeneration.

The development of modern science has depended strongly on specific features of the cultures involved; however, its results are widely and trans-culturally accepted and applied. The science and technology of electricity provides a particularly interesting example. It emerged as a specific product of post-Renaissance Europe, rooted in the Greek philosophical tradition that encourages explanations of nature in theoretical terms. It did not evolve in China presumably because such encouragement was missing. The trans-cultural acceptance of modern science and technology is postulated to be due, in part, to the common biological dispositions underlying human cognition, with generalizable capabilities of abstract, symbolic and strategic thought. These faculties of the human mind are main prerequisites for dynamic cultural development and differentiation. They appear to have evolved up to a stage of hunters and gatherers perhaps some 100 000 years ago. However, the extent of the correspondence between some constructions of the human mind and the order of nature, as revealed by science, is a late insight of the last centuries. Quantum physics and relativity are particularly impressive examples.

Ancient Greek philosophers were the first to postulate the possibility of explaining nature in theoretical terms and to initiate attempts at this. With the rise of monotheistic religions of revelation claiming supremacy over human reason and envisaging a new world to come, studies of the natural order of the transient world were widely considered undesirable. Later, in the Middle Ages, the desire for human understanding of nature in terms of reason was revived. This article is concerned with the fundamental reversal of attitudes, from “undesirable” to “desirable”, that eventually led into the foundations of modern science. One of the earliest, most ingenious and most interesting personalities involved was Eriugena, a theologian at the Court of Charles the Bald in the 9th century. Though understanding what we call nature is only one of the several aspects of his theological work, his line of thought implies a turn into a pro-scientific direction: the natural order is to be understood in abstract terms of ‘primordial causes’; understanding nature is considered to be the will of God; man encompasses the whole of creation in a physical as well as a mental sense. Basically similar ideas on the reconciliation of scientific rationality and monotheistic religions of revelation were conceived, independently and nearly simultaneously, by the Arab philosopher al-Kindi in Bagdad. Eriugena was more outspoken in his claim that reason is superior to authority. This claim is implicit in the thought of Nicholas of Cusa with his emphasis on human mental creativity as the image of God’s creativity; and it is the keynote of Galileo’s ‘Letter to the Grand Duchess Christina’ some 800 years later, the manifesto expressing basic attitudes of modern science. -/- This article in English is based on the monography (in German): A. Gierer “Eriugena, al-Kindi, Nikolaus von Kues - Protagonisten einer wissenschaftsfreundlichen Wende im philosophischen und theologischen Denken”, Acta Historica Leopoldina 29 (1999), Barth Verlag in MVH Verlage Heidelberg, ISBN: 3-335-00652-6, which is also available online on this server. -/- -/- .

Georg Ernst Stahl (1659-1734) was a German physician and chemist. The book (in German) documents a symposium of the Academy Leopoldina on his works and thoughts that contributed to the Enlightenment. Der weite Horizont seines Denkens und seiner Arbeiten umfasst die Phlogiston-Theorie der Verbrennung, die später mit der Entdeckung des Sauerstoffs widerlegt wurde, aber dennoch wichtige Erkenntnisse zur Reversibilität von Reaktionen und zur unsichtbaren Persistenz der beteiligten chemischen Komponenten beitrug. Seine Gedanken zur Rolle der „Anima“, die heute überholt erscheinen, führten bereits am Beginn des 18. Jahrhunderts Konzepte ein, die für die moderne Biologie und Psychologie von Bedeutung sind. Dazu zählen etwa Homöostase, Synergie, die Vorbereitung willentlicher Bewegungen und Unterschiede zwischen unbewussten aber vernünftigen Handlungen und solchen, die von rationalen Erwägungen geleitet werden. Stahls medizinisches Hauptwerk ist die „Theoria medica vera”, Halle 1708. Eine der zentralen Publikationen zur chemischen Theorie der Verbrennung ist die „Zymotechnia fundamentalis seu fermentationis theoria generalis”, Halle 1697, in deutscher Sprache 1734. Siehe auch „Georg Ernst Stahl (1659-1734), German Physician and Chemist“, Artikel von A. Gierer, in: Encyclopedia of the Enlightenment (Hg. A.C. Kors), Bd. 4, Oxford University Press, New York 2003, S. 124-125.

Socioeconomic inequalities are functions not only of intrinsic differences between persons or groups, but also of the dynamics of their interactions. Inequalities can arise and become stabilized if there are advantages (such as generalized wealth including “human capital”) which are self-enhancing, whereas depletion of limiting resources is widely distributed. A recent theory of biological pattern formation has been generalized, adapted and applied to deal with this process. Applications include models for the non-Gaussian distribution of personal income and wealth, for overall economic growth in relation to inequalities and for effects of uncoupling strategies between developing and developed countries. Note added after publication: The equations (14) for the model of the income distribution, with its characteristic non-Gaussian extension towards higher incomes (fig.4), are closely related to the Fokker-Planck equation that is widely applied in many fields of physics.

The paper addresses the formation of striking patterns within originally near-homogenous tissue, the process prototypical for embryology, and represented in particularly purist form by cut sections of hydra regenerating, by internal reorganisation of the pre-existing tissue, a complete animal with head and foot. The essential requirements are autocatalytic, self-enhancing activation, combined with inhibitory or depletion effects of wider range – “lateral inhibition”. Not only de-novo-pattern formation, but also well known, striking features of developmental regulation such as induction, inhibition, and proportion regulation can be explained on this basis. The theory provides a mathematical recipe for the construction of molecular models with criteria for the necessary non-linear interactions. It has since been widely applied to different developmental processes.

Full applicability of physics to human biology does not necessarily imply that one can uncover a comprehensive, algorithmic correlation between physical brain states and corresponding mental states. The argument takes into account that information processing is finite in principle in a finite world. Presumbly the brain-mind-relation cannot be resolved in all essential aspects, particularly when high degrees of abstraction or self-analytical processes are involved. Our conjecture plausibly unifies the universal validity of physics and a logical limitation of human thought, and it does not regard consciousness -the most basic human experience - as a marginal phenomenon.

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation.

Applying mild methods of preparation, part of the ribosomes of rabbit reticulocytes are found in aggregates (later called polyribosomes) of up to six ribosomal units. Upon treatment with RNA-ase, they desintegrate into single ribosomes. The fast-sedimenting aggregates are found to be more active in protein synthesis in terms of incorporation of radioactive amino acids, whereas the single ribosomes are more receptive to stimulation by the artificial messenger RNA poly-U. The findings indicate that the linkage of ribosomes into aggregates is due to the messenger RNA. They support a tape-reading mechanism of protein synthesis whereby growth of the peptide chain is accompanied by shifting the active site of the ribosome from one coding group of nucleotides of the messenger RNA to the next.

Modern science, based on the laws of physics, claims validity for all events in space and time. However, it also reveals its own limitations, such as the indeterminacy of quantum physics, the limits of decidability, and, presumably, limits of decodability of the mind-brain relationship. At the philosophical level, these intrinsic limitations allow for different interpretations of the relation between human cognition and the natural order. In particular, modern science may be logically consistent with religious as well as agnostic views of humans and the universe. These points are exemplified through the transcript of a discussion between Kurt Gödel and Rudolf Carnap that took place in 1940. Gödel, discoverer of mathematical undecidability, took a proreligious view; Carnap, one of the founders of analytical philosophy, an antireligious view. By the time of the discussion, Carnap had liberalized his ideas on theoretical concepts of science: he believed that observational terms do not suffice for an exhaustive definition of theoretical concepts. Then, responded Gödel, one should formulate a theory or metatheory that is consistent with scientific rationality, yet also encompasses theology. Carnap considered such theories unproductive. The controversy remained unresolved, but its emphasis shifted from rationality to wisdom, not only in the Gödel-Carnap discussion but also in our time. -/- .

This is an English translation of my essay: Alfred Gierer Wissenschaft, Religion und die deutungsoffenen Grundfragen der Biologie. Mpi for the History of Science, preprint 388, 1-21, also in philpapers. Range and limits of science are given by the universal validity of physical laws, and by intrinsic limitations, especially in self-referential contexts. In particular, neurobiology should not be expected to provide a full understanding of consciousness and the mind. Science cannot provide, by itself, an unambiguous interpretation of the natural order at the philosophical, cultural and religious level. The diversity of interpretations, however appears as a positive factor of cultural dynamics. Historically, the revival of the philosophy of nature in the middle ages included remarkable biological thoughts such as those of Eriugena and Thierry of Chartres. In this essay, emphasis is placed on basic issues of modern biology – the distinction of man and animal, the evolution of human mental capabilities, the physics of the universe as precondition for biological evolution, and the intricasies of the brain-mind-relation. They are open to agnostic as well as religious interpretations, the individual choice being mainly a matter of wisdom and not just of knowledge. -/-.

An English translation of the essay and an extended introduction are included in the download. In diesem Essay geht es um ein religionsfreundliches Selbst- und Weltverständnis, das die Reichweite der menschlichen Vernunft ebenso wie deren intrinsische Grenzen achtet. In dem weiten Feld wählen wir hier Betrachtungen des mittelalterlichen Philosophen und Theologen Meister Eckhart aus. Eckhart (ca.1260-1338) gilt vielen als Mystiker, anderen als Philosophen des Christentums. Er war wohl Beides. Philosophisch ist seine Lehre, die einzelne menschliche Seele habe einen göttlichen, unvergänglichen Urgrund; eher mystisch die These, dieser Urgrund bedarf einer „Gottesgeburt“ in der Seele, ein Loslassen von allen Bestrebungen, einschließlich dem Bestreben, sich gottgefällig zu verhalten. Mir geht es hier nur um den philosophischen Aspekt mit Betonung auf Erkenntnis.

Nikolaus von Kues ist eine der faszinierendsten Persönlichkeiten im Übergang vom Mittelalter zur Neuzeit. Während seine theologischen und neuplatonischen Vorstellungen viel beachtet werden, gilt das weniger für seine naturphilosophischen Ideen: Wie Gott die Welt in Wirklichkeit, so schafft der Mensch sie in Gedanken. Beobachtung, Experiment und Mathematik sind zum Verständnis der Natur notwendig. Die biblische Überlieferung ist nicht wörtlich zu nehmen. Er propagierte ein fast unendliches Universum ohne Mittelpunkt und Begrenzung mit einer sich bewegenden Erde. Besonders bedeutsam im Hinblick auf Reichweite und Grenzen moderner Naturwissenschaft ist seine Theorie des "Wissens vom Nichtwissen": Wissenschaft selbst ist geeignet, ihre eigenen Grenzen zu erkennen. Die Schrift würdigt auch die Persönlichkeit des Cusanus und schließt mit einem Essay über die Beziehung von Naturwissenschaft und Religion in unserer Zeit. The booklet is a re-edition of sections on Nicolas de Cusa in my book "Die gedachte Natur" (1991), also in philpapers. Cusanus was of one of the most original philosophers of the early Renaissance. He gave reasons for human self-confidence: as God created the world order in reality, man creates it in his mind. Not only mathematics, but also quantitative experiments, are essential for understanding nature. Human rationality is superior to verbal interpretations of the Bible: the universe is almost infinite, with no limits and no centre, and with a moving earth. And he insisted on what he considered to be the highest form of knowledge: the knowledge of the limits of knowledge, with far-reaching implications for the philosophy of nature and human cognition.

Der Text ist eines von achtzig Kurzessays zum Thema „Was ist der Mensch“, zu denen unsere Arbeitsgruppe „Humanprojekt“ der Berlin-Brandenburgischen Akademie der Wissenschaften eingeladen hat. So genau Aussagen inhaltlicher Naturwissenschaft oft sind, auf der metatheoretischen Ebene bleibt die Gesamtheit unseres Wissens, und damit auch die Stellung des Menschen in der Natur deutungsfähig und deutungsbedürftig; sie ist mit verschiedenen, natürlich nicht mit allen, philosophischen, kulturellen und religiösen Interpretationen vereinbar; erkenntnislogisch gesehen dürfen und können wir wählen. Worum es dabei eigentlich geht, ist Lebenskunst, die Frage nach der guten Art zu leben, und deshalb plädiere ich im Zweifelsfall für metaphysischen Optimismus. Der Mensch kann fast im platonischen Sinne das Mentale und damit die Beziehung seines Bewusstseins zur gedanklichen Ordnung des Naturgeschehens betonen, und er muss sich auch nicht die religiöse Frage verbieten, was diese Verbindung für ihn bedeuten kann. Was die Ethik angeht, so ist Gemeinsinn eine wertvolle, aber knappe Ressource unserer biologischen Spezies „Mensch“, die eher behutsam und mit Rücksicht auf natürliche Anlagen des Menschen zu aktivieren ist.

• Aggregates of previously isolated cells of Hydra are capable, under suitable solvant conditions, of regeneration forming complete animals. In a first stage, ecto- and endodermal cells sort out, producing the bilayered hollow structure characteristic of Hydra tissue; thereafter, heads are formed (even if the original cell preparation contained no head cells), eventually leading to the separation of normal animals with head, body column and foot. Hydra appears to be the highest type of organism that allows for regeneration of the entire structure from random cell aggregates. The system is particularly useful for studying cell interactions, tissue polarity, pattern formation, and cell differentiation.

While many different mechanisms contribute to the generation of spatial order in biological development, the formation of morphogenetic fields which in turn direct cell responses giving rise to pattern and form are of major importance and essential for embryogenesis and regeneration. Most likely the fields represent concentration patterns of substances produced by molecular kinetics. Short range autocatalytic activation in conjunction with longer range “lateral” inhibition or depletion effects is capable of generating such patterns (Gierer and Meinhardt, 1972). Non-linear reactions are required, and mathematical criteria were derived to design molecular models capable of pattern generation. The classical embryological feature of proportion regulation can be incorporated into the models. The conditions are mathematically necessary for the simplest two-factor case, and are likely to be a fair approximation in multi-component systems in which activation and inhibition are systems parameters subsuming the action of several agents. Gradients, symmetric and periodic patterns, in one or two dimensions, stable or pulsing in time, can be generated on this basis. Our basic concept of autocatalysis in conjunction with lateral inhibition accounts for self-regulatory biological features, including the reproducible formation of structures from near-uniform initial conditions as required by the logic of the generation cycle. Real tissue form, for instance that of budding Hydra, may often be traced back to local curvature arising within an initially relatively flat cell sheet, the position of evagination being determined by morphogenetic fields. Shell theory developed for architecture may also be applied to such biological processes.

The book (in German) on “Solar Energy – challenge for research, development and international co-operation” is the report of a study group of the Akademie der Wissenschaften zu Berlin. It reviews solar thermal, photovoltaic, and bio mimetic solar energy techniques; prospects of de-central techniques in developing countries; transport and storage of solar energy; and chances for cooperation with Arabic countries and countries of the South of the former Soviet Union. The prospect of large scale energy production in arid areas, and the modern potentials of conducting electricity over long distances by high-voltage DC transmission (V, 2.1) are particularly relevant for the concluding section. Political chances as well as risks were considered for reliable long term cooperation with various Arab countries on these issues. The recommendations appear to be still appropriate 25 years after the book was published, particularly the political advice in favour of cooperation between Europe and suitable countries of the Maghreb. The global time scale of implementation (discussed in chapter I, 7.2) is of the same (high) magnitude as that of other major changes in the history of technology, such as the substitution of sailing ships by steamboats which took almost a century.

The essay is an English version of the German article "Wissenschaftliche Rationalität, menschliches Bewusstsein und pro-religiöse Ideen". It discusses immanent versus transcendent concepts in the context of the art of living, as well as the understanding of human consciousness in the context of religion. Science provides us with a far reaching understanding of natural processes, including biological evolution, but also with deep insights into its own intrinsic limitations. This is consistent with more than one interpretation on the “metatheoretical“, that is on the philosophical and cultural level, including liberal, enlightened forms of religion as well as agnostic views. Choices and preferences are mainly a matter of wisdom and art of living, and not just of knowledge, and this, in my view, supports metaphysical and anthropological optimism as expressed in liberal pro-religious ideas. Within Christian theology, metaphysical optimism and openness are most characteristic for the ideas of “apokatastasis” – “salvation for all” - repeatedly condemned as heretical, but also widely supported from early Christianity to modern times.