Chemical Ambition: The Ethical Playground of Synthetic Biology

1. Synthetic Biology and the Chemical Ambition to Create Artificial Life ‘Are you playing God?’ • Joachim Schummer • University of Karlsruhe (KIT), Germany, js@hyle.org • "Ethical Cases for Chemistry Education"Aalborg University, Copenhagen, Denmark, 16-17 June 2017

2. Introduction: Chemistry in the public view • There is long history of the demonization of chemistry, alchemy and chemical crafts - the most forceful moral verdict in Christian culture, e.g. • The story of the Fallen Angels (devils) who teach women the secrets of Creation (chemical crafts of the 3rd century BC). • Church Father Tertullian's conviction of dying wool, an alliance with Satan. • Late medieval and early modern criticism of alchemist, devilish tempter. • Faustian pact with the devil. • 19th-century mad scientists/chemists tempted by a fiendish alien. • Chemists should be aware of their public image, avoid any work or allusion that might raise the public concern, of which "playing God" is just one version. • However, the longing for media attention is tempting!

3. Outlook • From Spontaneous Generation to Synthetic Biology • Ethical Analysis of the Creation of Life • Conclusions • Joachim Schummer: Das Gotteshandwerk: Die künstliche Herstellung von Leben im Labor, Suhrkamp: Berlin, 2011.

4. I. From Spontaneous Generation to Synthetic Biology • Until the 19th century, people believed that simple organisms spontaneously generate out of non-living matter everywhere, that the creation of life is a banality. • Witnessed in ordinary experience • mold, worms, flies, bugs, lice, frogs, mice etc. seemed to spontaneously emerge. • Described in Holy Sciptures • e.g. Moses 2: frogs out of water, mosquitos out of dust. • Book of Law of Manu (Hinduism): certain living beings emerge out of warm moisture. • Explained by natural philosophers, particularly by Aristotle.

5. Bugonia: The Art of Making Bees • Since Vergil (70-19 BC), instructions for making bees belonged to the standard repertoire of agricultural textbooks. Konrad von Megenburg (German cleric, 14th century): "Bees emerge out of the bellies of young cows [...]. You need to cover the bellies with muck to get bees. Beesalso generate from the buried skin of oxes; Wasps from the skins of donkeys. Worms out of the muck of pigs; frogs out of turnips or chard; horseflies out of bad air or rotten breath [...] From the body of dead horses you get wasps and hornets, from the body of donkeys you get a kind of flies called glow worms [...]. Note that the bees, which generate from cows, propagate and that their offspring are of similar kind as real bees." [Book of Nature, ca. 1350]

6. Novel Appreciation of Basic Living Beings through Evolution Theories in the 19th c. According to the evolution theories of Lamarck and Darwin, simple living beings are evolutionary precursors to humans. Now the artificial creation of the simplest organisms could be considered a first step to the creation of humans, a scandalous competition with divine Creation. Criticism of the idea of spontaneous generation grew. • Louis Pasteur (1864): • “Take a drop of sea water […] that contains some nitrogenous material, some sea mucus, some ‘fertile jelly’ as it is called, and in the midst of this inanimate matter, the first beings of creation take birth spontaneously, then little by little are transformed and climb from rung to rung – for example, to insects in 10,000 years and no doubt to monkeys and man at the end of 100,000 years.” • “What a triumph, gentlemen, it would be for materialism, [...] Of what use then would be the idea of a Creator-God?”

7. The Fascination with "Artificial Life" during the 20th Century • Throughout the 20th century, scientists promised they would soon be able to create life in the laboratory. • The media frequently reported on "artificial life", e.g. • Chemically induced cell division of unfertilized eggs of sea urchins (parthenogenesis) (1900s, Jaques Loeb) • Synthesis of cell membranes, vesicles (1910-30s, Langmuir) • biochemical synthesis of DNA/RNA fragments, genetic engineering (1950-70s, Ochoa, Kornberg) • cloning of mammals (1980s) • „artificial life“: computer simulation of life processes, "life in silicio" (1980s) • ACS President Charles C. Price called for "Life Synthesis" as a national goal (1965).

8. Danielli's Amoeba: Popularization of Science through Ethics (1970) • "First synthetic cell" • James Frederic Danielli (1911-84) • Media Response • membrane • Danielli's Warnings and Visions • such experiments are dangerous, should be controlled by the state; • „synthetic biology“ creates new organisms for technological ends (health, food, energy, environment, computer, etc.); • ... and new, "better" humans. • nucleus • cytoplasm • „Biochemistry: Straight to Hell“

9. Jack Sztosak • Steen Rasmussen • 2. Synthetic Genomics • originally: genetic modification of standard organisms (yeast, bacteria) to reconfigure their metabolism (metabolic engineering) • now: genetic de-novo-creation of a new minimal organism, on which any metabolism can be attached. • Craig Venter • Tom Knight Two Main Branches of Contemporary „Synthetic Biology“ • 1. Protocell research • originally: chemical evolution, studyingthe origin of life under prebiotic conditions • now: creation of life under any possible condition • Synthetic biology differs from its original research fields by emphasizing the creation of life.

10. Media response to a press release of 20 May 2010 • “Craig Venter plays God”(Süddeutsche, Germany) • “The new Dr. Frankenstein”(Berliner Kurier, Germany) • “Man Plays Creator”(Times of India) • “Frankenstein bacteria”(Volkskrant, Netherlands) “Are scientists playing God?”(Sun, England) • „Craig Venter, Satan of the biotech age“ (Standard, Austria) • “The Game of being God”(Vanguardia, Spain) • “The Catholic Church has said that the creation of the first ever synthetic cell could be positive so long as the discovery is used 'for the good of all'.”(Christian Today) • "Church warns cell scientists not to play God"(ABC News, Associated Press)

11. Daniel Gibson What did the Venter Team do in May 2010? Combining 3 different results from former research Total genome analysis of bacteria species A Total genome synthesis of bacteria species A Inserting genome A in bacteria B, (but now with synthetic genome A after slight modification) "first self-replicating synthetic bacterial cell"? • Hamilton O. Smith • J. Craig Venter • & 21 other researchers

12. Genome synthesis from "4 bottles of chemicals"? • The genome of Mycoplasma contains about 1 million base pairs • Buy 1,000 gene sequences of each 1,000 base pairs:1,000 x 1,000 bp • chemical synthesis of sequences of each max 200 bp • enzymatic linking yields sequences of each 1,000 bp • Combining 10 sequences yields 10,000 Bp: • Combining 10 sequences yields 100,000 Bp: • Combining 10 sequences yields 1000,000 Bp: • The linking and multiplication of the sequences (steps 2-4) were performed in living yeast cells. • 100 x 10,000 bp • 10 x 100,000 bp • 1 x 1,000,000 bp

13. How was the synthetic genome inserted? • Like plants and other organisms, most bacteria have impermeable cell walls. However, Mycoplasma has only a membrane, comparable to soap bubbles, and no nucleus. • After chemical treatment of the membrane, two Mycoplasma bacteria sometimes merge to build one cell. • While merging two bacteria, particles in the environment(here: synthetic genomes) can happen to slide in. • The next cell division sometimes result in a cell with the inserted genome only. • If the inserted genome contains an antibiotic resistency, all other bacteria can selectively be killed.

14. Did the Venter team "synthesize a cell"? • Unlike the press release and the media reports, the scientific publication just claimed that it only appears, "as if the whole cell was created". • In fact, only a genome, i.e. a complex biopolymer molecule, was synthetized with chemical and biochemical methods and inserted into a host-cell to make a hybrid bacterium. • In biology and breeding, the genomic creation of hybrids is known since many decades, with well-known limits, i.e. hybridazation is possible only with very few pairs of species.

15. What was the scientific merit? • All steps had been performed and published before, were mostly based on decades-old standard procedures. • However, taken together they demostrated for the first time the extremely small error rate of both genome analysis and synthesis, enabled by new intermediary error corrections. • The survival of the hybrid bacterium ("creation of a cell") was not the scientific purpose, but only a means to the end of demonstrating the feasibility of the method. • The confusion of means and ends was a strategy to raise media attention.

16. II. Ethical Analysis of the Creation of Life • "Playing God" • Undermining the dignity of life • Biocentric ethics - individualism • Biocentric ethics - holism • Bioterrorism • Risks for laboratory staff

17. 1. The Prohibition of "Playing God" • Argument: The artificial creation of life is said to be forbidden, because that would claim to be like God. • Problems • 1. Biological: Biology holds that life originally emerged by chemical evolution rather than by divine Creation. • 2. Ethical: For atheists and Christians who do not believe in the divine Creation of bacteria, like almost all Christians up to the 19th century, the prohibition is based on wrong assumptions. • 3. Theological: The religious prohibition only refers to the claim of being like God. If one does not claim so, one is not affected. • However: Some scientists (e.g. Venter) subtly play with indirect allusions of playing God in order to raise media attention for their research. • Summary: Argument is not generally acceptable and rarely applicable.

18. 2. Undermining the Dignity of Life • Argument: If life can be synthesized in the laboratory, it is said that it would lose its dignity, which is considered bad. • Problems • 1. The argument typically confuse the dignity of bacteria with the dignity of humans by relating the creation of bacteria to the creation of humans ("Frankenstein"), which is scientifically unfound. • 2. Human practice (e.g. the use of pesticides, antiseptics, antibiotics) widely ignores and negates the dignity of basic organisms. • 3. If the dignity can be uphold only by ignorance (unwillingness to know that bacteria can be synthetized), it is ethically questionable. • Summary: The argument ist too weak, not really ethical, and based on confusions.

19. 3. Biocentric Ethics - Individualism • Biocentric positions in ethics hold that all living beings (as opposed to mere things) have inherent value, from which moral norms are derived: • Respect for living beings (Albert Schweitzer) • Commandment of not doing harm to living beings • Responsibility for living beings (Hans Jonas) • Commandment of taking care of the existence and well-being • Estimation of living beings(various positions, e.g. Paul Taylor) • Commandment of considering the existential interests of living being in all decisions.

20. 3. Biocentric Ethics - Individualism • Respect and Responsibility for living beings have no normative implications on the artificial creation of living beings. However, once they are created, respect and responsibility would also apply for artifical life. • From the estimation of living beings one could derive an appeal in favor for synthetic biology to multiply life by artificial creation, because that would multiply what is estimated. • Summary • Biocentrism is either irrelevant or suggests an appeal for the creation of life. • Biocentrism was developed in order to protect existing life, rather than regulating synthetic biology.

21. 4. Biocentric Ethics - Holism Holism (e.g. "Deep Ecology") estimates the evolutionary process of life (or living nature) as a whole, instead of individual organisms. Argument: If the artificial creation of life has a negative impact on the process of life, by interaction with natural organisms on the genetic or ecological level, it would be prohibited. Problems Many human activities massively interact with life, e.g. agriculture, horticulture, forestry, breeding, genetic engineering, use of antibiotics, antiseptics and pesticides. Evaluation problems: How to distinguish between positive and negative impacts on the evolutionary process of life? Prediction problems: How to calculate the impact of artificial organisms on the process of life?

22. 4. Biocentric Ethics - Holism Predictive Approaches (rules of thumb) The more similar the artificial organism is to natural ones, the easier it is to estimate ecological and genetic interactions (cf. classical genetic engineering). The more different it is, the more unpredictable are the interactions, but also the more unlikely. The simpler the artificial organism is, the more unlikely is its survival because of lack of adaptability to the environment. Summary Protecting the integrity of life as an evolutionary process could establish the responsibilty to avoid negative and unpredictable interactions. However, the approach remains vague in practice and differs not much from that for genetic engineering.

23. 5. Bioterrorism • Argument: Terrorists could use the knowledge and skills of synthetic biology to develop novel organisms for infectious deadly diseases (bioweapons). • Problem of proportionalityIt seems much easier to collect existing pathogenic germs (e.g. ebola virus) than creating a new one in the laboratory. • However: There is an urgent need for international regulation of gene synthesis companies, their clients and orders with regard to pathogenic genes. • Thusfar, there are only national recommendations and voluntary commitments by companies.

24. 6. Risk for Laboratory Staff • Experimenting with potentially pathogenic organisms is very dangerous and should be performed only under extremely safety measures. • The risk must be balanced against the potential benefit of resulting knowledge.

25. III. Conclusion • The creation of simple organisms was considered a banality up to the 19th century, which required no moral or theological regulation. • Only with the biological theories of evolution, attention was paid to simple organisms as a first step towards the development of humans. Since then, both scientists and the public have been fascinated with the creation of life. • Classical deontological ethics ("playing God", dignity of life, biocentricsm) do not provide ethical regulation for the creation of life. • From the integrity of life as a whole, as well as from the risks of bioterrorism and laboratory research, moral restrictions and vague rules of responsibiliy can be derived, hardly different from GE. • Public media excitement ("playing God") fails to address ethical issues and misreprensents science. • Media excitement misguides scientists searching for public attention,is harmful for both ethics and science.

26. III. Conclusion: Ethics, Science and the Public • draws attention • Public • Science • makes moral judgements • ethical analysis, information, interaction • analysis • information, interaction • Ethics