Truth in science and in molecular recognition, post‐truth in human affairs
Marc H.V. Van Regenmortel · Journal of Molecular Recognition · 2019
The search for truth as the supreme achievement of the human mind has had a chaotic history in the Western world from ancient Greece to modern science and to philosophy of science in the 20th century and finally to contemporary postmodernism. This short review will describe how scientific laws were transformed into continuously improving approximations of truth and into intuitive metaphoric descriptions of scientific reality. When Donald Trump in 2017 withdrew the United States from the United Nations Paris Agreement to combat climate change, it became clear that there had been a declining trust in formerly respected sources of factual and scientific information and that science denialism was leading to an enormous development of irrational and systematic post-truths that are partly politically motivated, The correspondence definition of truth states that the truth of a proposition or a sentence is determined by the extent to which it corresponds to the reality of what is perceived by a human mind. Our sensory organs passively detect objects in our environment, and they will inform us of the truth that snow is indeed white. Human perception, however, also involves the deciphering and interpretation of what is sensed, and this leads to cognition when thoughts and concepts are elaborated in the brain. These give us some knowledge about the reality that surrounds us, although we do not perceive objects as they really are but only as they appear to us. Schroeder's reversible staircase is a well-known example of the power of visual interpretation for identifying what is seen.1 Scientists tend to be realists and accept that objective verifiable observations as well as invisible concrete objects exist even if we can only observe them indirectly with the help of tools and scientific instruments that must be handled correctly. Such interpretations require scientific training because they lack the self-evident truth value of observational statements that visibly correspond to a reality that can be observed with unaided senses. Since scientific theories elaborated with abstract concepts and theoretical terms cannot possess the logical validity of deductive arguments, the reliability of many scientific theories often remains uncertain. A scientific theory consists of a cluster of interrelated models together with various hypotheses that link these models with actual systems in the real world. These links are not logical connections but imprecise relations of similarity between a model and a real system.2 (p85) The logical empiricist Hempel3 (p28) proposed that one could transform an inductive generalization (all swans that we have seen are white) into a true general law, which could then make it possible to argue by deduction that every swan is necessarily white. However, this short-lived attempt to use induction to reach logical certainties was soon rejected because it became obvious that if scientists wanted to further develop their theories, they had no choice but to go on collecting additional empirical evidence that was necessarily obtained by induction. As a result, scientists always remained at the mercy of newly obtained empirical evidence that could contradict the latest version of their theory. When scientific theories have been confirmed by multiple observations and experimentation, they may achieve a high level of predictive success, although they will never produce absolute certainty. The history of science is littered with theories that used to be believed and were considered to be useful although they are now known to be false. In many cases, these theories and their underlying concepts, such as phlogiston, ether, vitalism, astrological predictions, the humoral theory of medicine, and spontaneous generation, had been considered to have scientific value, although they were never based on valid, credible, and reliable observations. The case of spontaneous generation is particularly interesting since for centuries it had been accepted that life was constantly being recreated on our planet! We had to wait until 1859 when Pasteur finally demonstrated that spontaneous generation was a myth by showing that an open flask containing broth that had been boiled did remain sterile indefinitely if the neck of the flask had a highly convoluted shape. After 160 years, the open flasks on view in the Pasteur museum in Paris have still not been contaminated by surrounding microorganisms, providing a visible demonstration of the correspondence theory of truth regarding the absence of spontaneous generation in biology. When a scientific theory fails to be consistent with newly obtained empirical evidence, there may be something wrong with the theory itself or with some of its numerous assumptions and hypotheses, which determine the range of conditions under which the theory is supposed to apply. It is always possible to modify some of these assumptions by introducing additional ad hoc hypotheses to rescue the theory when incompatible experimental results are obtained since otherwise the theory would have to be considered falsified and had to be abandoned. An interesting example is Einstein's theory of relativity, which predicted that light would be attracted by heavy bodies such as the sun, a phenomenon that became testable during the 1919 total solar eclipse. On that occasion, it was indeed observed that light was bent by the gravitational pull of the sun, which actually was incompatible with Newton's laws of motion and universal gravitation and seemed to falsity them.4 (p15) However, Einstein's theory described what happens at the speed of light in the environment of stars and galaxies, whereas the Newtonian laws, which deal with bodies that move much more slowly, were still valid for sending a spacecraft and Neil Armstrong to the moon 50 years later. Subsequently, quantum mechanics was developed for explaining the behaviour of atoms and molecules, and it became clear that no single scientific theory, even string theory, could account for the phenomenon of gravity present at all the different scales in the universe. The fact that science only produces theories that remain approximatively true, however, has the unexpected beneficial consequence that scientific progress always remains possible. As pointed out by Klee5 (p227) about no scientific account of any phenomenon is "literally" true. When electrons are said to orbit a nucleus, this statement must be understood only metaphorically as if little planets were moving around a star. The whole of molecular biology has been made accessible by using metaphors that give us the intuitive illusion that we understand biological phenomena, although we are actually unable to explain them in terms of their complex physical reality. Calling biology "molecular" is already a reductionist illusion since the emergence of biological entities and phenomena that arise from their underlying chemical constituents and laws does not really provide us with a complete understanding of their intrinsic biological reality (6, 7 Lily Kay8 in her book Who Wrote the Book of Life described the many metaphors used in molecular biology that seem to justify the assumption that both the genetic and verbal information systems that are based on a linear alphabet are analogous. However, a language presupposes an interlocutor and a comprehending brain, and a code requires an emitter and a recipient, and it is not clear how the knowledge of a genetic language could develop prior to its construction by conscious humans. According to Kay,8 (pp296-325) the Book of Life metaphor produces information without meaning, codes with no language, messages with no sender, and writing devoid of authorship. Since recognition is a cognitive capacity of higher organisms endowed with consciousness, it makes, for instance, little sense to say that proteins recognize other proteins and that antibodies recognize their corresponding antigens and attack them when they are present at the surface of infectious agents such as viruses. The metaphor of biological recognition is widely used in biology to describe the stereocomplementarity between molecules that bind to each other, and such reactions are said to be specific or even to mimic the fit between a lock and a key. Such images can be deceptive because they do not take into account that the recognition process often involves an induced fit that results in considerable changes in the structure of the binding regions of the two partners after they have interacted with each other.9 In the case of microorganisms and viruses that cause animal and human diseases, the infectious process is often described as a battle between the pathogen and specific antibodies produced by the immune system of the host. Such a metaphor attributes a cognitive capacity and a goal-directed intentionality to molecules and organisms in order to explain biological phenomena that are devoid of any such anthropomorphic features. To attribute a purpose to a pathogen or to an immune system is entirely subjective since a purpose has no real existence outside the mind thinking of it.10 Darwinian natural selection occurs blindly by preserving what is useful for living organisms and eliminating what is not useful and is harmful. It is also inappropriate to try to explain the behaviour of passive, nonliving agents such as viruses and molecules by attributing to them metaphoric intentions and goals that are assumed to help them overcome imaginary enemies.11 Metaphors are often useful as epistemic or heuristic devices, but they do not in any way tell us how the world actually is.6 In recent years, the classical view of a gene as a discrete element in genomes has been challenged by the ENCODE Project Consortium.12 Initially, a gene was viewed as a linear DNA sequence that was transcribed into a single RNA transcript using the genetic code and was then translated into a messenger RNA and eventually into a functional polypeptide that could determine a phenotypic trait in an organism. During the transcription from DNA to RNA, the initial RNA is first processed to become a mRNA capable of directing the synthesis of a protein, but this involves the splicing out and removal of a number of RNA sequences called introns. This produces a shorter RNA molecule made up of the remaining sequences called exons that become connected to each other during the splicing process. A phenomenon called alternative splicing frequently occurs when numerous different distant regions in the RNA sequence are removed as introns, which leads to large numbers of unpredictable mRNA molecules that will be translated into very dissimilar proteins. This means that a single gene commonly encodes large numbers of different mRNAs and protein products of different sizes with the result that it is then impossible to determine where a gene actually begins and ends. Additional difficulties also arise because some genes can overlap one another and can share the same DNA sequence in a different reading frame or on the opposite strand. Furthermore, when regulatory elements of a gene such as promoters and enhancers have not been localized in the genome sequence, it is difficult to decide if they should be allocated to one particular gene. The ENCODE Project Consortium12 has proposed the following definition of a gene: "The gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products." However, by sidestepping the complexity of gene regulation and intermediates transcripts, such a definition is not a helpful guideline for identifying genes in the thousands of genomes that are currently being sequenced Thomas Kuhn13 in his book The Structure of Scientific Revolutions, argued that scientists in their research are always guided by paradigms that correspond to theoretical presuppositions that determine which lines of investigation they choose to pursue. When vaccinologists try to develop an HIV vaccine, they may select a particular experimental strategy based, for instance, on cellular immunity or on the induction of protective antibodies because they believe that such an approach is most likely to succeed. If their initial results are negative, they nevertheless tend to remain committed to their chosen paradigm because they believe that a certain strategy with its numerous variations must be pursued long enough to have any chance of success. Unfortunately, after 25 years of well-funded, high-quality research, a successful HIV vaccine remains elusive, and this has been attributed to the fact that invalid paradigms had probably been pursued.14, 15 The paradigm known as structure-based reverse vaccinology (SBRV) advocated the study of crystallographic structures of complexes between HIV spikes and neutralizing monoclonal antibodies (nMabs) derived from HIV-infected individuals in order to be able to design a vaccine by reverse molecular engineering.16, 17 This approach was called rational vaccine design because it was assumed that if an epitope present on an HIV spike reacted strongly with a nMab, it would also be able to elicit similar antibodies when it was used as a vaccine immunogen. The term rational design is borrowed from rational drug design, which is a structure-based and computer-assisted strategy used in drug development.18 A rational procedure is often believed to be superior to an empirical one, although this overlooks the fact that a rationally designed vaccine must necessarily always first be tested empirically to demonstrate its efficacy in the biological context in which it will be used. The label rational vaccine design is in fact not appropriate because SBRV only attempts to improve the chemical antigenicity of an epitope (ie, its binding capacity) and does not investigate the numerous mechanism of the immune system that are responsible for its ability to induce neutralizing antibodies.19 In order to make a truly rational design decision, it is not sufficient to optimize epitope-paratope fit since it is also essential to have a complete understanding of all the complex inner workings of the immune system, a knowledge that clearly is not available. Herbert Simon20 pointed out that humans actually only possess what he called a "bounded rationality" because human cognition is always constrained by limited resources, inaccurate information, and insufficient time to fully dissect highly complex dynamic systems. This has led to the suggestion that many biological systems may be too complex to be fully comprehended by human intelligence.21 Such a viewpoint is in line with chaos theory, which established that extremely minute differences in the initial conditions of any complex system always have a huge impact on its subsequent state.22 This explains why we are unable to make long-term predictions of physical systems (the weather), economic systems (the stock exchange), and biological systems (a vaccination trial). An example is the RV 144 HIV vaccine trial started in Thailand in 2004, which was immediately criticized as being unjustified by 28 senior vaccinologists from 22 institutions23, 24 although it was the only HIV vaccine trial that 5 years later showed a modest success.25 It is also remarkable that the unsuccessful SBRV approach was pursued for more than 15 years, although its underlying paradigm was shown to be incompatible with well-established immunological theory such as the degeneracy of the immune system and the polyspecificity and heterospecificity of antibodies.26, 27 However, these shortcomings have never been recognized or addressed by the proponents of SBRV .19 Since the scientific attitude demands a commitment to both established scientific theories as well as to accumulated empirical evidence when repeated failures are observed,4 (pp47-50) the pursuit of SBRV may have been an instance of confirmation bias, which leads investigators to give more weight to invalid pre-existing beliefs than to negative empirical evidence. The phenomenon called post-truth rocketed to public attention in November 2016, when the Oxford Dictionaries named it the 2016' s word of the year. Post-truth refers to circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief. The prefix "post" is meant to indicate that truth has been eclipsed and has become irrelevant while facts are subordinate to political views.28 (pp1–15) The Brexit vote and the US presidential election in 2016 had seen an obfuscation of facts and outright lying that were unprecedented. Donald Trump, for instance, falsely claimed that he had won the biggest electoral victory since Reagan and that his inauguration was the largest in US history. The daily lies of Trump were such obvious falsehoods that their credibility could have been easily disputed but he paid no political price for this and his popularity remained unaffected. In the UK, during the Brexit referendum campaign, Boris Johnson falsely claimed that the UK was paying 350 million pounds a week to the European Union and that this amount would become available if the UK left the EU.28 (p5) This outright lie did significantly influence those who voted for leaving the EU. The growth of the internet and of social media have also led to an enormous spread of misleading and false information that is circulated with the intention to deceive.29 In today's political climate, it has become acceptable to openly question the scientific opinions of experts and to give equal credit to the biased views of scientists recruited by industry who are paid to propagate an attitude of science denialism in order to promote the economic agenda and financial interests of large companies. The first major example of an orchestrated science denial campaign occurred in 1953 when the Tobacco Industry Research Committee (TIRC) recruited scientists for producing fake arguments that challenged scientific papers linking cigarette tar to cancer in laboratory mice. The mission of the TIRC was to convince the public that there was no scientific consensus that cigarette smoking caused cancer while at the same time trying to prevent politicians from adopting policies that would damage the economic interests of tobacco companies.28 (pp21-24) Although this TIRC campaign was partly successful, additional damaging scientific evidence continued to accumulate, and the tobacco companies in 1998 finally agreed to pay a $200 billion settlement that shielded them from future lawsuits. During the court case, thousands of documents were released by the TIRC indicating that they had known the truth all along; however, the companies continued to sell their products to a worldwide market since their profits were adequate for paying for the ever-increasing number of lawsuits. As described in the Merchants of Doubt,30 the same "tobacco strategy" was used by some of the same people for fighting the increasing controversy over global warming. In 1998, the American Petroleum Institute conveyed a series of meetings attended by representatives of the major oil companies to discuss potential industry responses to the major climate Kyoto Protocol treaty that aimed to reduce global emissions of greenhouse gasses. 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