1923

1. The Role of Experiments, Preconceived Ideas, and Scientific Authorities in Early Controversies about the Origin of Life and the Creation of Artificial Life in the Laboratory Ute Deichmann Jacques Loeb Centre for the History and Philosophy of the Life Sciences, Ben-Gurion University of the Negev, Israel

2. 1923 1936

3. The question of the origin(s) of life has occupied scholars and scientists since ancient times. • For centuries, it had been dominated by the general belief in the spontaneous generation of various forms of life.

4. Outline: • Origin of life through spontaneous generation; the examples of evolutionary biology and cell biology • Experiments and preconceived ideas – reviewing the controversies on Pasteur • From spontaneous generation to the creation of artificial life

5. 1.Origin of life through spontaneous generation; the examples of evolutionary biology and cell biology Spontaneousgeneration: Doctrine that organisms, such as insects, worms, mice, microorganisms, arise from non-living sources, e.g. mud, putrifying animal or vegetable matter • Aristotle (384-322 BCE) • The early Church Fathers (ca. 300-400 CE) • Doctrine was finally abandoned in early 20th century

6. First major blow to this doctrine regarding larger anmals by Francesco Redi (1668): • Flies are only found in the samples exposed to the air, not in those protected from the air. • Conclusion: They do not arise spontaneously, but only from eggs (observed under the microscope)

7. Extensive discussions on the origin of life in the 19th century Concerned with • the supposed formation of infusoria and micro-organisms from particles of organic matter • cell theory

8. Spontaneous generation and theory of evolution: Lamarck: Philosophie Zoologique 1802: Nature is producing species of animals in a progressive way, beginning with the most imperfect or simple and ending with the most perfect that is the most complex one. But the more primitive forms of life did not disappear. Solution: Spontaneous generation

9. Spontaneous generation and theory of evolution: • Oken 1805: proposed his idea of an “Urschleim”, from which primitive forms of life were generated. Was later taken up by... • Haeckel: integrated it into his theory of “Monera”. Primitive living beings which supposedly consisted only of a small homogeneous mass of protoplasm and built the basis of life. Protistologists: All “Monera“ forms contain single or multiple nuclei. Concept was abandoned. • Darwin accepted possibility of spontaneous generation through the 1870s. Remained ambivalent thereafter, trying to avoid this question.

10. Spontaneous generation and cell theory: Schleiden, Schwann 1838: Theory for the generation of cells as structural elements of organisms and for their role in the development of form. Concept of de novo formation of cells by crystallizing out from a continuous and formless matrix.

11. Schleiden hoped that “that natural science may be able one day to regard the cell as the necessary form of a normal condition of a permeable (assimilated organic) substance, just as the crystal is a necessary form of the inorganic substance. Then would all individual and simple cells originating and existing in organisms be but a definite organic crystallization.” • Schwann believed that “organisms are nothing but the form under which substances capable of imbibition crystallize.”

12. Schwann’s and Schleiden’s predilection with the cell’s de novo generation and crystallization • Fitted the ideas of the spontaneous generation of micro-organisms and that of neoplasms as new formations of tumours • May be related to their strong adherence to Kantian and Friesian philosophy of the unity of nature, • Might have been influenced by the romantic school of natural philosophers (e.g. Lorenz Oken), • Obscured the “fundamental significance” of cell theory (E.B. Wilson,1928)

13. An early critic: • Robert Remak • Rejected Schwann’s theory of de novo cell formation from the beginning, • Rejected Virchow’s et al.’s theory of the new formation of neoplasms of tumours. “The origin of cells de novo is no more credible than the spontaneous generation of life” (1852).

14. 1850 -1900: • The notion of cells from crystallisation was replaced by the notion of cells from the division of pre-existing cells. (Remak 1852, Virchow 1855: Omnis cellula e cellula) • The doctrine of spontaneous generation continued to be upheld by many in regard to micro-organisms.

15. 2. Experiments and preconceived ideas – reviewing controversies on Pasteur • Experiments of Pasteur in 1861 are considered crucial by many for the final abandonment of the doctrine of spontaneous generation.

16. Pasteur: "On the organized bodies which exist in the air: Examination of the doctrine of spontaneous generation" (1861): • Micro-organisms do not generate in a boiled bouillon as long as dust was prevented from entering it. Dust carries micro-organisms. • Micro-organisms, too, do not arise from inanimate matter but only from existing ones of the same kind.

17. Some historians’ assessments: • Pasteur allowed his research to be guided by his preconceived idea and ideological bias against spontaneous generation (e.g. Farley 1978, Geison 1995). • Background: The debate on spontaneous generation in 19th century France was related to a larger debate about a materialistic and religious way of life. • Spontaneous generation was embraced by anti-religious scholars, because it rendered life a merely physical process based on chance events. • As a member of the French cultural establishment Pasteur resented these materialistic views.

18. My comments: Pasteur had not only • ideological reasons for disliking spontaneous generation. but also • scientific reasons for disliking it: Wide knowledge on fermentation and micro-organisms (e.g. their constancy and specificity) ► conviction that a spontaneous generation of micro-organisms was highly unlikely.

19. Pasteur’s experiments were conducted with a preconceived idea. • This did not render his experiments questionable, because they were accompanied by wide knowledge, logical designing of the experiment and skills. • His opponents, too, had preconceived ideas, but often lacked his other attributes. • Experiments alone were not able to disprove spontaneous generation. • Increasing knowledge in micro-biology and biochemistry together with logical reasoning and clear experimentation led to the final abandoning of spontaneous generation.

20. The abandonment of the ideas of spontaneous generation of life and cells was a pre-requisite for scientific research into the artificial creation of life in the laboratory. • The question of the origin of life became related to that of the artificial generation of life in the laboratory.

21. 3. From spontaneous generation to the creation of artificial life

22. A. The primacy of form and growth in the morphological-colloidal-mathematical approach (early 20th century) Around 1900: Scientists tried to mimic features of life, especially growth and form on the basis of osmotic growth and the colloidal concept of nature. 1864 Moritz Traube: First scientific study of artificial semi-permeable membranes and first experiment-based physicochemical theory of cell growth; mimicked the growth of plant forms.

23. French physicist Stéphane Leduc: • “Traube made the first artificial cell, ... This remarkable research should have been the starting-point of synthetic biology.” (1911) • 1912 La BiologieSynthétique

24. Leduc, La Biologie Synthétique, 1912 Fig 32. - Croissance osmotique de chlorure et nitrate de manganèse avec capsules terminales présentant un haut degré d'organisation.

25. Leduc 1912: • Transformation of substances leads to an increase of osmotic pressure in the tissues: “transformation of chemical energy into osmotic energy”. • No clear boundary between “life and physical phenomena”. • Virchow’s “toute cellule vientd'une cellule” is an error of reasoning; cells can be created differently. Leduc promoted an entirely morphological-physical concept of life and neglected novel concepts (e.g. individuality of chromosomes; specificity of enzyme reactions).

26. B. The specificity of basic structures and processes in the molecular approach (early 20th century) The notion of the relevance of specific molecules for an understanding of basic features of life preceded macromolecular chemistry. German American physiologist Jacques Loeb: “The living cell synthesizes its own complicated specific material from indifferent or non-specific simple compounds of the surrounding medium, while the crystal simply adds the molecules found in its supersaturated solution. This synthetic power of transforming small ‘building stones’ into the complicated compounds specific for each organism is the ‘secret of life’ or rather one of the secrets of life.” (Loeb 1916)

27. Loeb rejected claims of the synthesis of life through osmosis: "The fact that the living cell grows after taking up food has given rise to curious misunderstandings. Traube has shown that drops of a liquid surrounded with a semipermeable membrane may increase in volume when put into a solution of lower osmotic pressure. This has led, and is possibly still leading, to the statement that the process of growth by a living cell has been imitated artificially. Only one feature has been imitated, the increase in volume; but the essential feature of the process in the living cell, i.e. the formation of the specific constituents of the living cell from non-specific products, has of course not been imitated." (Loeb 1916)

28. Loeb held that the artificial creation of life was not only a physical process, but had to involve the synthesis of specific molecules, in particular self-replicating DNA (“nuclear material”). “Nobody has thus far succeeded in this, although nothing warrants us in taking it for granted that this task is beyond the power of science.” (Loeb 1909)

29. Similar contrasting themes (Holton) or basic beliefs (Polanyi) were prevalent in subsequent stages of research on the origin of life and creation of artificial life:

30. Predilection for the concept of unity in nature Descriptive, mathematical, colloidal approaches Emphasis on physical concepts of life, e.g. growth and form Predilection for the distinction between living and non-living nature Mechanistic experimental approaches Emphasis on chemical concepts of specificity of structures and molecules ---------------------------------- • Crystallization of cells from unspecific fluids • Synthesis of life by osmotic growth • Schleiden, Pouchet, Haeckel, Leduc, Thompson ------------------------------------ • Cells only from existing cells of the same type • Synthesis of life by synthesis of specific macromolecules • Remak, Pasteur, Loeb, Wilson,

31. The different approaches have not been equally successful. • In 2010, around 100 years after Loeb’s prediction, a completely chemically synthesized DNA, which was fully functioning, was successfully transferred into a bacterial host cell by Craig Venter and his team.

32. Science. 2010 July 2Creation of a bacterial cell controlled by a chemically synthesized genome. • Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC

33. Outlook: Research in modern synthetic biology can be fruitful for solving basic questions on evolutionary biology and the origin of life. Questions • When will it be possible to synthesize a whole organism? • Will this be the same life as that which has evolved for 3-5 billions of years?

34. THANK YOU!