Valdemar W. Setzer
Dept. of Computer Science, Institute of Mathematics and Statistics, University of São Paulo
Original:- Sept. 11, 2000, this version: May 5, 2010
See also the Portuguese version
Brazilian biological research became worldwide famous with the publication of a paper on the July 13, 2000, issue of the journal Nature, even deserving a cover ("Citrus pathogen sequenced"). It was the paper describing the completion of the DNA sequencing of the bacterium Xilella fastidiosa, which attacks orange trees, the first time a plant pathogen had its DNA sequenced. It was the outcome of a giant effort directed by the São Paulo State Research Foundation (FAPESP) and coordinated by the biologist Andrew Simpson, the first author of that paper. For the first time, a complete genome was sequenced in a distributed way: more than 30 labs were involved in the project. New sequencing methods were developed by Simpson and his colleagues.
Andrew Simpson gave a lecture on that research on May 25, 2000, at the Institute of Physics of my university. His first slide had the title "Life Defined." He said "For the first time we are able to define life." After the lecture, I asked him what he thought of the following contents of a slide projected by Hugo Armelin, a leading biochemist at my university, during a lecture he gave at my institute: "The genome determines the organism’s behavior." Simpson confirmed, and said something like the only origin of the differences between him and famous Brazilian former soccer player Pelé is their genes.
Coincidentally, just before Simpson’s lecture I finished reading an extraordinary book by Harvard professor Richard Lewontin, The Triple Helix - Gene, Organism and Environment, Cambridge: Harvard Univ. Press, 2000. On page 10 he writes: "One of the most eminent molecular biologists, Sydney Brenner, speaking before a group of colleagues, claimed that if he had a complete sequence of DNA of an organism and a large enough computer then he could compute the organism." And follows with "A similar spirit motivates the claim by yet another major figure in molecular biology, Walter Gilbert, that when we have the complete sequence of the human genome ‘we will know what is to be human.’"
In issue number 102 (Feb. 16, 2000) of his excellent electronic magazine Netfuture (see www.oreilly.com/~stevet/netfuture), which I strongly recommend to everybody interested in "technology and human responsibility," Steve Talbott brings a collection of 8 citations along the same line. I am going to transcribe here just one of them, spoken by James Watson, exactly one of the two people who discovered the DNA, and director of the National Center for Human Genome Research: "I mean, sure, we have great respect for the human species … But evolution can be just damn cruel, and to say that we've got a perfect genome and there's some sanctity to it, I'd just like to know where that idea comes from. It's utter silliness. And the other thing, because no one really has the guts to say it, I mean, if we could better human beings by knowing how to add genes, why shouldn't we do it?"
These statements – from Simpson’s up to Watson’s – have no scientific basis. Lewontin shows that the environment is absolutely essential for the development of any organism, that is, DNA alone does not determine it. As a matter of fact, DNA without its environment in a cell produces absolutely nothing. Moreover, by "environment" of a whole organism one should not just understand the climate, geography, etc., but also a consequence of the organism itself. Each organism influences the environment, so that the latter is unpredictable, resulting from the interaction of the organism with what is around it. "Jurassic Park" cannot occur, because it does not suffice to have a dinosaur’s DNA, it is necessary to have the "living" cell of a dinosaur egg to produce a dinosaur. Finally, proper environment conditions for dinosaurs – created in part by themselves –, should be present, otherwise no dinosaur could subsist. The same considerations are valid for the local environment of any internal part of a living organism.
Back to Lewontin, he goes much farther. He says that even if we knew the genes and the micro- and macro-environment it would not possible to foresee the development of an individual organism. He says that in this development something completely unknown acts randomly upon the organism during its development, the so-called "noisy development." This is something completely unknown which acts randomly in parallel to the interaction of genes and environment, producing unpredictable changes in the organism. As an example, he mentions the fruit fly’s sensorial bristles below the wings; in average, the numbers of bristles to the right and to the left of the wings are the same, but in each individual those numbers may vary, giving for instance 9 on one side and 5 on the other. The cells on both sides have exactly the same genes, "… and it seems ridiculous to say that the developmental environment – the temperature, humidity, oxygen concentration, and so on – was different on the right and left sides of an insect that is two millimeters in length and one millimeter in width and developed its bristles while adhering by its ventral surface to the inside of a glass culture vessel in the laboratory. So the variation is a consequence of neither genetic nor environmental variation. It is developmental noise, a consequence of random events within cells at the level of molecular interactions" (p. 36, his emphasis). A little further he mentions that each of those bristles originates out of 3 cells, which result from 2 subdivisions of a precursor cell. These cells have to migrate during development, but the skin surface hardens with time. If the subdivisions take too long, those cells don’t reach the surface soon enough to generate a bristle. "Such random processes must underlie a great deal of the variation observed between organisms, including variation of their central nervous systems." Then he makes considerations on the development of brain neurons: "But the connections must be randomly formed before they can be stabilized by experience. Such a process of neural development could give rise to differences in cognitive function that were biological and anatomically innate, yet neither genetic nor environmental. I am certain that even if I had studied the violin from age of five, I could not play a Paganini caprice as Salvatore Accardo does, and Accardo do doubt has neural connections that I lack and has them since an early age. But it is by no means clear that those anatomical differences between us are genetic" (p. 38, my emphasis). Recall the Simpson vs. Pelé case… apart from Pelé’s environment, in the city of Santos, where every boy has certainly played soccer at the beach. I doubt that his parents had ever heard of Biology; probably Simpson’s (who lives in Brazil but I think was born in England) parents would never incentive him to become a soccer player. Attention to what follows: "The organism does not compute itself from the information in its genes nor even from the information in the genes and the sequence of environments. The metaphor of computation is just a trendy form of Descartes’ metaphor of the machine. Like any metaphor, it catches some aspect of the truth, but leads us astray if we take it too seriously." He is referring here to the fact that an essential part of Descartes’ Method is to regard living beings as machines.
Speaking about the environment’s influence on development, Lewontin mentions research done with plant clones (for those plants that create roots when one of its branches is planted, producing a clone is absolutely trivial). Planting clones in various elevations, one does not observe that the smaller (taller) plants in a certain elevation produce the smaller (taller) plants in every elevation. There are unpredictable factors involved in the interaction with the environment (p. 23).
But he does not stop at environmental factors. He has a whole chapter titled "Parts and whole, causes and effects" criticizing research of parts of an organism when trying to reach its whole. "To be ‘parts’ things must be parts of something. That is, there are no parts unless there is a whole of which they are the pieces. For biological systems, because the hierarchy of functions and because of the multiple intersecting causal pathways, the determination of parts is made only after the appropriate ‘whole’ is defined" (p. 79, my emphasis). "There are no universal rules for cutting up organisms" (p. 87). "The reductionist world view that dominates our investigation of nature ordinarily leads that investigation to proceed in two stages. To begin there is a downward analytic process that breaks the whole into its constituent parts, which is then followed by a synthetic phase in which the causal pathways among the parts are discovered" (p. 80). He proceeds to speak about the solar system, which is expressed in masses, distances and velocities, and in p. 93 returns with "The problem of biology is that the model of physics, held up as the paradigm for science, is not applicable because the analogues of mass, velocity, and distance do not exist for organisms. … The characteristic of a living object is that it reacts to external stimuli rather than being passively propelled by them. An organism's life consists of constant mid-course corrections." Continuing the previous sequence: "Biological investigation, in contrast, often begins with an upward synthetic process, in which objects and phenomena are thought to be parts, but the whole of which they are parts is as yet undetermined. As in a play by Pirandello, they are characters in search of an author. The Human Genome Project, whose goal is to sequence all of the DNA of a human genome (actually a composite of a number of different humans) is precisely of this form. … Next, this sequence must be broken into pieces of various lengths that correspond to functional units, the genes and their regulatory elements. There are signals internal to the sequence that provide guesses about the boundaries of the part of a gene that is translated into protein, but these are only guesses and can only be confirmed when a protein is actually found in the organism. Moreover, it is virtually impossible to tell where the boundaries of regulatory sequences are … Thus it is impossible to know how to break up a DNA sequence into genes before we know how the cell reads different parts of the DNA in the process of making protein. But this is only the first step. Even after we identify all the genes as functional units in the production of proteins, we will not know the function of those proteins. We will then not know how to assemble the collection of genes and their proteins into functional subsystems with pathways of causal connections. Rather, we will be in the situation of the paleontologist who knows that Stegosaurus had large bony plates along its back but must ask the question, ‘What are they for?’ In Biology, this ‘what for’ question is not the same as it is in the analysis of the parts of a motorcar or a clock. In the latter case, the functions are known in advance and it is certain that all the internal parts serve one or another of these functions. In the case of organisms … In addition, it is by no means true that every part serves a function. … Only a quasi-religious commitment to the belief that everything has a purpose would lead us to provide a functional explanation for fingerprint ridges or eyebrows or the patches of hair on men's chests. In biology we cannot escape from the dialectical relation between parts and whole. … The hand is the appropriate unit of investigation if we are concerned with the physical act of holding, but the hand and eye together are an irreducible unit for understanding how we come to seize the object that is held" (pp. 81-82).
As a matter of fact, it was precisely because of these problems that Goethe wrote that the scientific method that is used with inanimate objects should not be applied to animated beings, and characterized what he called "typus" (he used the Latin word, instead of the German equivalent), an extension of the same concept introduced by Aristotle. He called the attention to the fact that in a living organism, there exists a unity which transcends the visible physical manifestation. Each part has to the focused from the perspective of that unity (which, for him, was non-physical, but subject to investigation through our thinking).
Back to Lewontin, "The machine model for life has led biologists to ignore one of the common characteristics of many physical systems, their dependence on initial conditions. … It is impossible to understand the situation of living organisms without taking into account their history. Populations subject to identical selective conditions may arrive at quite different evolutionary endpoints, so that the observation that two species differ is not prima facie evidence that they were adaptively differentiated. There are many cases in which related groups of species have a great variety of forms of the same basic feature, but in which there seems no way to provide a special story of selection for each form" (p. 89).
Soon after Armelin’s lecture mentioned in the beginning, I sent an e-mail to my department colleagues, commenting on the lecture. I wrote that it seemed to me that soon after World War II nobody would risk to say that we are determined just by our physical characteristics (at that time, race, color, nose length, etc.). Well, Lewontin confirms that idea and formulates it with greater precision and knowledge: "Up until Second World War biologists, especially geneticists, were for the most part biological determinists who ascribed to genes the chief causal influence in molding social, psychological, and cognitive differences between individuals. Then, as the consequences of the biological theories of race and character in hands of the National Socialists became widely known, there was a general revulsion against biological determinism and it was replaced by a widespread environmentalist explanation of social facts. But this environmentalist dominance was short-lived, and within twenty years of the end of the war, genetic explanations again came to dominate, in no small part because psychology and sociology failed to produce a coherent predictive scheme for human psychic and social development. The reigning mode of explanation at present is genetic" (p. 16, my emphasis).
He speaks highly interesting things about mutations. For instance, each one occurs in just one instance of DNA. This leads me to conclude that genetic modifications changing all the DNAs in the body or in an organ will probably be possible only at the level of the spermatozoid, or of the unfertilized and fertilized eggs, therefore "improved" humans will all be fertilized "in vitro."
Finally, Lewontin has a chapter "Directions in the study of biology," where he starts by saying that in the first chapters he showed that "a reductionistic approach to the study of living organisms can lead us to formulate incomplete answers to questions about biology or to miss the essential features of biological processes or to ask the wrong questions in the first place" (p. 109). I have been insisting a long time on what I consider a "wrong question," "How do neurons generate human thinking?" and the limitations which it causes in research. He analyses various attempts at formally solving biological questions, such as Catastrophe and Chaos theories, showing that they have not lead to a comprehension of nature. He then proceeds to analyze the problems with research. "One of the consequences of the internal heterogeneity is that functions cannot be understood without information about shape and form. … But, as chemistry invaded biology toward the end of the nineteenth century, with the consequence that organisms came to be seen as collections of molecules, questions of form were de-emphasized in favor of the study of molecular reactions. Form again came to play some role in reductionist biological explanation with the development of the biochemistry of macromolecules in the last hundred years. … The culmination of that interest in form came with the discovery of the three-dimensional structure of DNA and the consequences of the structure for explanations of DNA replication and coding. Yet, ironically, the understanding of the role of DNA in biology has led to a scheme of explanation that pays minimal attention to molecular structure and the spatial relations of molecules. The central dogma of molecular biology is that the chemical sequence of nucleotides in DNA determines the chemical sequence of amino acids in proteins which in turn uniquely determines the function of the protein. … It is part of the substrate of our understanding of biochemistry that the folded three-dimensional shape of a protein is critical in its function. Yet that understanding does not enter in an integral way into biological explanation. … if we want to understand which protein is produced from a gene, we must investigate the complete chain of production in its spatial and temporal detail. The folding of proteins also depends upon the cell environment. … These understandings, however, have not penetrated into the main structure of biological explanation" (pp. 114-117, my emphasis). Note what he says on the appearance of form in embryos: "It is very well to say that certain genes come to be transcribed in certain cells under the influence of the transcription of certain other genes, but the real question of the generation of form is how the cell ‘knows’ where it is in the embryo. … the normal organism is the nexus of a large number of interacting forces that are individually weak" (p. 118). He gives a lot of importance to the fact that the forces which act upon organisms are "weak" ones.
Evolutionary genetics professor John R.G. Turner, of the University of Leeds, commenting on Lewontin’s book says (my translation from an article published in the newspaper Folha de S.Paulo, 4/23/2000, section Mais, pg. 27 – by the way, the article that lead me to Lewontin’s book): "The next stage requires that biologists concentrate less upon molecular sequences (which seem to be the answer, but are not) and return to the more traditional disciplines, such as the study of the three-dimensional form applied to molecules, embryos and organisms."
Based upon all this I may state the following:
1. It is not possible to say, in any way, that the form of an organism is determined by its DNA, much less its behavior. It is known that changing the DNA, the organism changes its form, but it is not possible to state that the form is due exclusively to the DNA. To me, this was clear from a philosophical point of view: a form is a model, an idea and thus it is not physical. What manifests itself physically is an approximation to the model, which is followed in this manifestation. To me, this manifestation results from the model, the genes and the environment, in a continuous interaction.
2. I think that biochemical connections among molecules and cell components are known, but it is not known when these connections are going to take place or are going to break. In Scientific American of June 2000 there is an interesting paper on cell communication. Some mechanism of signal transmission into the cell was discovered, and this causes the cell to produce proteins. But, again, this is a quite approximate knowledge; it is not known when the process takes place, why it takes place in some cases but not in others, what cell elements are going to be involved, etc.
3. In his talk, Hugo Armelin mentioned the cell processes of differentiation (the cell remains as it is), mitosis (cell subdivision, preceded by DNA subdivision) – which originates cell multiplication, and cell death (apoptosis). For what I know, it is not possible to examine a cell and its environmento and predict which of the 3 processes is going to take place in the next instant. That is, one does not know how the cell "decides" to contribute to form, not even for a simple leaf. If even the form of a living organism is not understood, what about its behavior?
4. Living beings are not machines, much less computing machines, as has been implied by much of what has been said on the DNA. I don’t know what is worse, believing that the DNA determines in an absolutely deterministic way any form or process in an organism, or that the brain is a digital computer. What digital machine is that one, having no signal synchronicity? Moreover, we don’t know any automatic machine which is self-determined, as anybody may innerly experience (by choosing the next thought); every machine that we can imagine (also abstract machines, both digital and analog) follow a rigid digital or analog program. Only 1,5% of our genes differentiate ourselves from chimpanzees. Come on, who may say that we are in our functions – and also appearance – just 1,5% different from them?
5. I think that one cannot rigorously speak about "natural selection" because, as shown by Lewontin, each organism influences its surrounding nature. Anyway, random mutations as the origin of changes within species, followed by natural selection is not convincing enough to explain evolution. For instance, it requires a multitude of simultaneous coincidental mutations.
6. There is a tremendous distortion in present biological research. The exaggerated focusing on DNA sequencing is dampening or eliminating other research directions.
7. I think that Darwinism had a deep "raison d’être": it wanted to induce, maybe even force, the idea that humans are just animals (to me, they are not). In other words, that there is no essential distinction – apart from physical complexity – between them and ourselves. This had its positive point, because it forced people to abandon old religious traditions, which have no place anymore in our present constitution. Our new inner configuration – which has been in progress since the 15th century, but whose development accelerated during the 20th century (see my essay "The obsolescence of education" on my web site), leads us to look for conceptual explanations and personal observations, and not to having dogmas or faith. (Nevertheless, traditional science has an absolutely clear dogma: its main point of view is that there are no processes which are not physical or chemical. How many scientists, reading these lines will eventually say "what a stupidity!" – what a prejudice!) Well, the situation is now much worse: statements, mainly those made by scientists (such as those mentioned in the beginning) try to induce, maybe force, the idea that living beings are machines, including ourselves. The problem is that there may be some ethics regarding animals, because they can suffer, in many ways similarly as we do. But there can be no ethics regarding machines (I am not referring here to their usage), as for instance having pity on disconnecting a machine. The image of humans being machines may also create this lack of ethics regarding humans, that is, there will be no pity in making them suffer or "switching off" some of them. Or, let’s use machines to educate human-machines, etc. ad nauseam. It seems to me that Darwinism has always been highly speculative, giving the impression that it is a great mental elaboration (a "descendent" tree – there is no agreement on its precise form – full of holes, the lost transitions between species…). One of its powers is its extreme apparente simplicity (mutations and natural selection, which anyone may understand). Nevertheless, there is nothing, absolutely nothing simple in nature; even a stone has undergone millions of years of extremely complex history in its formation. Another strength of arguments based upon the DNA resides in the fact that there is much more science, much more Mathematics behind it (the nucleotides sequences form a formal language). Worst of all, there is much more technology involved, the computer-based sequencing machines. W.Fischer, a biologist at the Institute for Biological Sciences at my university, told me that DNA sequencing machines have become like voltmeters: every biology research lab has to have one (and every lab at his institute has in fact at least one).
8. Let’s recall what Lewontin has mentioned as "noisy development" and the problem of how the cell knows where it is located in the embryo, added to what Armelin told about the three processes of cell life, that is, the "decision" of a certain cell remaining as it is and being used for tissue differentiation, or starting to subdivide (mitosis), or starting to die (apoptosis). It is precisely in those phenomena that something non-physical may act upon the cell, because in a decision process, a choice in the realm of ideas, it is not necessary to spend energy. I have to admit as a working hypothesis that the human being may have free will, because I experience this fact in myself when I decide to consciously choose my next thought. It does not matter that a biologist tells me that there is some unknown physical process in my brain taking the decision for "me." This is absolutely not what I observe when I control my thinking, recognizing that there is absolutely nothing that forces me to choose between two mental activities, for instance concentrating for some time my thinking on the number 2 or the number 5, if I initially choose these two numbers, and then decide to imagine the form of just one of them; to experiment this mental exercise, it is necessary to initially choose two numbers which have no connection to memories or preferences). Freedom cannot arise from our genes or from the environment; its origin has to be non-physical. Physical "laws" are implacable, they don’t permit freedom. Maybe they permit some randomness, but I don’t feel randomness in my own conscious decision processes leading to mental concentration on a certain thought. If we would primarily act in a random way, we would certainly destroy ourselves.
9. Maybe many biologists don’t know that they are influencing the way humanity regards itself. If they were aware of this fact, they would be more careful with what they say and write. Armelin mentioned, with apparent approval, if not enthusiasm, a phrase he projected taken from a recent Science magazine issue (or it was Nature, it does not matter): "The function of the brain is to perpetuate the species." Oh, come on! Maybe a mouse brain has indeed this function (I don’t agree with it), after all, animals practically live to survive and perpetuate their species. But what is the size of a rat’s brain? The size of a couple of peas? But then, why do we need a brain the size of ours???
10. Maybe many biologists don’t know that this influence may be (and I think it is) extremely harmful to humanity. What Nazis did is going to be peanuts regarding what we may expect in the future, maybe of what is already happening in some places. In the USA, the rate of suicide attempts among teenagers is – hold your breath – twice as big as the sum of the rates of the 21 most industrialized countries! In the USA, there are 1.6 million imprisoned people. Every month one reads that in some country economic differences between poor and rich are increasing, with the latter becoming even poorer. There has never been such an enormous consumption of hard drugs as there is today, destroying millions of lives. Fanaticism and fundamentalism are continuously increasing.
11. I am not against research. But I am strongly against the mistification of its results, as it has been happening with DNA, mainly regarding how the way of thinking of laymen is being influenced. I am also against forced directing of research towards a restricted area (who is going to refuse equipped labs, a budget to pay technicians and materials, working in a "hot" area with guaranteed publications, etc.?).
Fortunately I am not alone, as Lewontin’s book and Turner’s article have shown – albeit moved by a different inspiration than mine. The forces that are behind technology and the mentality that humans are machines are infinitely intelligent, but they have no common sense, and always end up exaggerating. It is not necessary to share my vision of the world to notice that there is a tremendous exaggeration concerning DNA: it suffices to know the area a little bit and use some common sense. Fortunately, many people have not lost completely their intuition to distinguish what is good and correct, and are starting to refuse transgenic plants. How long is it going to take until these plants start producing disasters? (For interesting holistic considerations on transgenic foods, I recommend the paper by S.Talbott and C.Holdrege "Golden Genes and World Hunger", in Netfuture 108 of July 6, 2000 – see its Internet address above.) But it seems to me that this intuition is not going to last very long; nowadays we cannot base our decisions upon traditions and intuitions, which have almost disappeared. It is necessary to deeply understand human nature to reach the conclusion that we are much more than what our genes form of ourselves, and how the environment influences us. Unfortunately, this understanding depends on a deep enlargement of the current scientific way of thinking and doing research.