Maximo Sandin, 2010
Interview with Máximo Sandín, PhD. in Biological Sciences and Associate Professor at the Faculty of Biology in the Universidad Autónoma of Madrid.
La Ciencia y sus Demonios, 25th September 2010.
1. In the last decade we have witnessed a boom in the genome sequencing of various organisms, which has left us with some quite complete databases. How do you think that information can affect the understanding of evolution's mechanisms?
I will respond with the words of scientists involved in this sequencing: they have had "profound evolutionary consequences." For example, the genome of the anemone, that originated 700 million years ago, has about 18,000 genes (humans have about 22,000) which code for proteins. "DNA blocks" that are present in man in the same arrangement have been found in the anemone genome. More than 80% of its introns are in the same places as in man and they have found 283 “genes” that are associated with diseases in humans, including one almost exactly like the BRCA2 “gene”, supposedly responsible for breast cancer.
These “building blocks” also exist in the sea urchin genome, which is 500 million years old. The number of protein coding genes is 23,500! of which we share 7,077, including those related to vision, smell and hearing but, above all, the Rag genes (which, as you know, evolved from transposons) involved in the immune response, and many other genes associated, in man, with diseases such as muscular dystrophy, and Huntington's chorea. It is not surprising that commentary on these discoveries in magazines such as Science has called them an "intellectual revolution".
But from the concrete point of view of studies directly relating to evolution, the sequencing of mammalian genomes has completely disrupted the old phylogenies. They have defined three superorders of mammals: Afrotheria (most African species), Xenartra (Central and South American species) and Laurasiatheria (mainly Eurasians). There is another very curious higher grouping, Boreotheria, which groups Laurasiatheria with Supraprimates which include rodents and primates. What is interesting is that studies of mammalian retrotransposons related to paleontological data indicate an “almost simultaneous” origin of these superorders.
To this must be added characteristics of genomes known for a long time, such as that genes are not "discrete" units, but are composed of DNA fragments, sometimes with many introns inside, sometimes scattered throughout the genome, and that they are subjected to "alternative splicing" (transcriptional and post-transcriptional), that is, to a kind of shuffling of its components, so that a sequence can encode hundreds or thousands of different proteins, which are expressed differently in each tissue and at each moment and that this expression is controlled by the entire genome, which includes what has been considered “junk” DNA until recently, through highly complex mechanisms (microRNAs, interference RNA, antisense RNA...). And this control is conditioned by the proteome and metabolome, in turn dependent on the conditions of the cellular environment and, therefore, of the external environment. And finally, we must add that genes operate in “networks” for the building of organisms. And all of the above is without accounting for epigenetic inheritance, also dependent on the environment.
The reknowned expert in evolutionary developmental biology Stuart A. Newman explains it brilliantly: "genes do not uniquely determine what is in the cell, but what is in the cell determines how genes are used"
2. Could you explain to us why you consider the modern synthesis, around which there seems to be a great consensus, to be inadequate for explaining evolution?
After our summarised and extremely simplified presentation of the explosion of empirical discoveries on the extremely complex control of genetic information, it would be an insult to the intelligence of biologists, with their knowledge the modern synthesis, to explain why the hypotheses on which it is based are not rooted in reality at all. But in case someone outside of professional Biology reads this, I will briefly try to explain it. The hypotheses on which population genetics (the pillar of the modern synthesis) was developed at the beginning of the last century assumed that genes were discrete entities, directly responsible for one characteristic with two variants, dominant and recessive. In a population "of infinite size" the frequencies of these variants would respond to the following relationship: p + q = 1. These would vary by individual and random point mutations, which are normally deleterious. But “in the event” that one of these mutations conferred “an advantage” upon its carrier, over time it would become the majority or the only one in the entire species. I imagine that no great capacity for reflection is required to understand that if the empirical data show this concept of "genes" to lack the faintest relationship to reality, all the elaborations built upon it will also be false, no matter how well the numbers come out.
3. Your criticism of "neo-Darwinism" is logically based on the invalidity of natural selection acting on random mutations as an evolutionary process. However, an organism originating through symbiosis, a characteristic acquired by horizontal gene transfer or any other mechanism that is responsible for the generation of new genetic information, is it not faced with natural selection for its survival in the population?
An organism originating through symbiosis, a characteristic acquired by horizontal gene transfer or any other phenomenon such as a duplication or a genomic reorganisation, phenomena for which there is abundant data, would not face natural selection. It would face the most terrible loneliness and misunderstanding (Goldschmidt's "hopeful monsters") if this occurred in a single individual. The point is that there is data that indicates that these changes can occur in groups of individuals, which produces a population with these changes. It has been experimentally verified that there are “hot spots” in genomes, sites where mobile elements tend to insert when they change location, where duplications or insertions of viruses tend to occur. Hot spots have also been found for horizontal transfer. That is, if these changes can make a population appear with new characteristics, it appears and that's it. Natural selection has no role to play in this process.
In fact, there is concrete data on these abrupt changes in populations. In research published last year in Nature, 100 phylogenies of animals, plants and fungi were studied. They found that in 78% of the "trees" the species appeared clearly due to sudden events. And they end with a very interesting reflection: “Speciation is freed from the gradual tug of natural selection, there need not be an ‘arms race’ between the species and its environment, nor even any biotic effects”.
4. One of the central pillars of Darwin's theory, and still in force, is that any modification - whatever its origin and size - that increases the probability of reaching reproductive age or improves it, will be positively selected for, while an alteration that reduces these factors will not be. Do you think that this concept is wrong in itself, or is it misunderstood in current evolutionary biology?
I do not think that this concept (if it can be called that) is wrong. It's a truism. It is evident that if a living being has a pathology, a defect or an unfortunate accident that prevents it from reaching reproductive age, it will not reproduce. What I cannot imagine from a biological point of view is what kind of modification a living being can undergo, whose natural condition is to reach reproductive age (if not, the species would not exist) such that a "modification" increases its probability of reaching reproductive age. In any case, this might be my problem, but I do not understand what this has to do with the genetic and embryological phenomena involved in evolution.
And yes, indeed, it seems that this is one of the "central pillars" of a 21st century theory of evolution.
5. I think you have postulated that the true architects of evolution are viruses, which allow the integration of complete and functional genomes in other organisms. What examples can we observe of specific functions or characteristics that have been achieved through the integration of viral genomes?
At the moment it cannot be said that I am the only one to uphold this claim. For example, Carl Woese, Luis Virarreal, Günther Witzany, Patrck Forterre, Nigel Goldenfeld, Philip Hunter, Peer Bork, to name a few prestigious virologists or microbiologists, have abundant publications in this regard. From these and other publications we can summarise some of the functions and characteristics you're asking about, for example:
- Characteristics of the eukaryotic nucleus not originating from bacteria, such as linear chromosomes, telomeres and telomerases, and separation of translational transcription are of viral origin.
- 10% of the human genome is made up of endogenous retroviruses that are expressed in all tissues and organs as a constituent and essential part, both in the adult state and, especially, in embryonic development.
- The introns have been shown to be of viral origin.
- Endogenous retroviruses have been found to encode microRNAs.
- Endogenous viruses have been shown to have genome editing capabilities.
- There are hundreds of thousands of scattered fragments of viruses that are constituents of the genome, especially their LTRs (“long terminal repeats”), which are regulators and promoters of other genes.
Regarding the proteome, it has been found that viruses code for glycosyltransferases, ubiquitin, DNA ligase, ribonucleotide reductase 1, SNF2 global transactivator, apoptosis inhibitor, chitinase, and UDP-glucosyltransferase. For example, prions, which are cellular communication proteins, are the capsid genes (NCp7) of HIV-1. The ERVWE1 gene of the endogenous retrovirus W capsid encodes syncytins, the proteins responsible for the formation of the syncytium-trophoblast. That is, they are involved in the formation of the placenta. There is a lot of literature on this question.
But if we follow the clues left by transposons and retrotransposons, it seems that they're finally recognised as of viral origin. This would mean that the vast majority of genomes in their real sense, that is, complete genomes (repeated sequences, LINEs, SINEs, introns, etc.) are of viral origin.
In short, it seems that there is data that gives viruses a worthy role in evolution.
6. The idea of viruses as “messengers” obliges us to think about the story of the chicken and the egg, since their genes must have been formed in some way. How do you think the first viruses or their precursors arose and evolved?
As I try to base what I propose on empirical, verifiable data, and not on speculation, I will answer in a very simple way: I have no idea. There is still no data to understand when, where and how viruses were produced. The speculation that they could come from cellular genes that "escaped" due to their "selfish" condition has collapsed with the discovery of millions of viral genes that do not correspond to any gene in living beings. Bacterial viruses (phages) are known to have been on Earth along with bacteria before life as we know it was possible, and their variety was very great from the beginning. Since we don't seem to have to invent an origin for them in order to understand their function, we will have to wait for new data.
7. I seem to remember reading that you do not defend the current position of epidemiologists, who tend to consider the intervention against pathogens as a battle, because these organisms (especially viruses) are generators of genetic diversity. Am I wrong? If not, then how do we proceed, both preventively and curatively, against these types of microorganisms that are found in all habitats?
I find it very curious when it comes to the current position of "epidemiologists." It's like when you talk about what "biologists" say, because just as there are biologists who firmly believe in certain things, there are (amongst us) many biologists (and more than you think) who do not "believe" in them. In the case of epidemiologists, there are many who closely follow the dictates of the pharmaceutical industry, but there are many others, highly qualified, who are very critical of them, as in the question of mass-vaccination campaigns. My contact with this issue and with critical epidemiologists came as a consequence of the shameful (and dangerous) papillomavirus mass-vaccination campaign and the murky circumstances & promotional nature of the of the Nobel Prize awarded to Zur Hauser. But when I learned of how vaccines were produced, I began to understand many things. For example, why influenza viruses are hybrids of humans and birds, or with sequences of pigs: they have made influenza vaccines by growing human influenza viruses in embryonic chicken eggs, and the new system is to grow them in cell lines. In both cases, the cultures are filled with fully active endogenous viruses and retroviruses. This explains the virus hybridisations, and it also explains why every year, with each new vaccination campaign, viruses “mutate”. By the way, in the 1980s Hillary Koprowsky manufactured a polio vaccine in a laboratory in the Congo using whole chimpanzee and green monkey kidneys, with their corresponding endogenous immunosuppression viruses, as substrate.
The association of viruses with certain diseases may be conditioned by the dominant warmongering conception of natural phenomena. Organs or tissues subjected to environmental stress or "aggression" have been shown experimentally to emit viral particles. That is why diseases such as cancer, arthritis, chronic fatigue syndrome and other even more absurd things are associated with a viral origin. The (provisional) conclusion that can be drawn from all this is that viruses associated with diseases would be viruses that have a specific function in organisms and their appearance is due to the fact that they have been subjected to environmental aggressions or some manipulation as described above.
And of course they are found in all habitats in more than astronomical quantities and with perfectly integrated functions in them. For example, in marine waters (I have not seen studies in fresh water) ten billion viruses per liter are involved in controlling the base of the trophic pyramid and preventing the excessive growth of bacteria and algae from hindering the entry of the solar rays necessary for marine life.They also control fundamental biogeochemical phenomena that include the role of sulfur derivatives that play a part in cloud formation. On land, the numbers and activities are similar (500 million viruses have been counted per gram of dry land). According to Carl Woese, possibly the most prestigious microbiologist of the current time, ecosystem viruses "constitute an important store and memory of genetic information in a community, contributing to the evolutionary dynamics and stability of the system." According to Luis Villareal of the University of California, 80% of the genes found in viruses in marine and terrestrial ecosystems do not correspond to any known gene.
We also have billions of viruses (phages) in our digestive system, which are the communication and control elements of bacterial colonies. Recently 3.3 million genes have been sequenced (150 times the human genome) belonging to the colonies of bacteria in our intestines that are so essential for life. That is to say, they are also our genome.
It seems clear that viruses are not pathogens by definition as, apparently, has already been assumed with bacteria (forty million bacteria have been estimated in a gram of soil and a million in a milliliter of fresh water, and in our organism it is estimated that there are ten times more bacteria than cells, but surely there are more). It is clear that if they were pathogens, we wouldn't survive for a second. And it also seems clear in light of the new data that there are many things we have taken for granted that we need to reflect upon.
8. Do you have any hypotheses to explain what happened during the so-called Cambrian explosion? Can you suggest any mechanism by which such spectacular diversity suddenly appeared in a relatively short period of time?
I have an explanation for the Cambrian explosion, which to is me very plausible (although, of course, I could be wrong), and is real according to the studies of Simon Conway Morris. But I don't know if it can be considered a hypothesis. What I have done is to trace the data until I arrive at a (possible) explanation. I will try to summarise this path:We know that there are viruses that contain, that encode functional sequences with specific biological content in eukaryotic organisms. We know that retrotransposons, from retroviruses, are responsible for DNA duplications in genomes. We know that the fundamental homeotic genes (there are other small or fragmentary ones) that control the development of tissues and organs and that, necessarily, were present in the Cambrian, are made up of sequences repeated in tandem and that in different organisms they differ by the number of duplications. So their content, their "meaning", would have to be contained in the original sequence of these duplications (in fact, endogenous retroviruses have great activity in embryonic development). This would explain the sudden appearance of different complex organisms from very simple ancestors. What is clear is that the highly conserved “building blocks” of developmental genes cannot have been produced by “random” mutations of the highly conserved bacterial genes of archaea and eubacteria that can still be identified in eukaryotic organisms. The (provisional) conclusion is that retroviruses are at the origin of developmental genes and that their insertions into the genomes of simple previous organisms can explain, by different combinations of them, the explosion of animal diversity in the Cambrian.
I understand that the phenomenon is very complex and difficult to "visualise" in the way that we have been taught evolution "should be", but the data are showing us extraordinarily complex biological phenomena that seem to clearly point in this direction. I believe that nothing is lost by daring to think about it, and perhaps it can help us to understand many other phenomena too.
9. Now we are going to travel much further back in time. Science still does not know for sure how life arose on our planet. Do you have any hypotheses that explain how that event occurred?
No. In this case I have no hypothesis either. What there is is infrared spectrum data on meteorites with a heavy load of water and organic matter. This spring [ April 2010 ], the finding was published in Nature that both are not only present but also “prevalent” on the 24 Themis asteroid. It appears to be widely assumed that Earth's water comes mainly from meteorites that impacted it (and as we know, seawater is a veritable “soup” of bacteria and viruses). I have read articles in Astrobiology, Cosmology and Astrophysics magazines that speak quite naturally of the origin of life in outer space. And bacteria and viruses were apparently on Earth before conditions existed for life as we know it. We also know that there are bacteria and, of course, viruses, which can perfectly resist radiation from outer space. We will have to wait for direct data on how the organic matter detected in asteroids is organised.
10. What is your opinion about Intelligent Design? Is it a scientific alternative to Darwinism as proposed by its proponents or is it something that belongs to the field of metaphysics rather than science?
Scientific activity consists of studying natural, material phenomena, to try to understand them as far as possible through observations or experiments that are verifiable or reproducible, that is, through material explanations based on material facts, and it will always be a partial, provisional explanation. (We know that there are other ways of accessing knowledge, but in this case we are talking about scientific practice, which is what I do or try to do). To resort to an abstract and all-powerful entity to explain what is difficult for us to understand or to explain with current means is outside scientific practice. Scientific activity consists of getting as far as the data and the means, the available techniques take us and if “everything” cannot be explained, we wait for new data or new technologies to allow us to continue deepening our knowledge (physicists know a lot about this, for example).
It is not scientific to invent so-called explanations or resort to rhetorical speculations to try to explain "everything" (and biologists have had overdoses of this for a long time). Now we have data and knowledge that is getting deeper every day, which were unthinkable a few years ago and which are showing very different from what was believed when we did not have the current technology. And these allow us to explain and understand many things, but logically not all things. We may never succeed. In any case, we will have to wait.
11. There are many who claim that science is in crisis, to the benefit of mythical thought and pseudoscience. Do you agree with this opinion? What kind of solution would you envisage for science to be perceived as something important by society?
Well, there are lots of people who think like this, but it seems to me that they are somewhat confused. At no time in history (at least in the so-called “advanced” countries) has science had so much social prestige as a carrier of Truth. You just have to take a look at the mainstream media. For many (perhaps those who feel "harassed") scientific thinking is the only modern way of thinking. The only path for capturing the essence of the World, of reality (the one path that does seem to be in crisis or, at least, in frank decline in society) is Philosophy.
Perhaps what those who hold this belief are referring to is the small, but growing, critical attitude towards certain applications of "science" and the search for alternatives. The enormous capacity for the circulation of information that has arisen as a result of Internet access has produced much “questionable” information, but it has also allowed the circulation of real news that does not usually appear in the mainstream media. For example, on the pernicious effects on health and the environment, proven by scientists, of transgenic products and their dire consequences for millions of small farmers. Or the scandals that are produced periodically by the terrible secondary (or principle) effects of certain drugs or the practices of the pharmaceutical industry in the Third World. The obvious economic component behind these industries makes many doubt the honesty of their intentions because when money and power are through ethics, truth, even Science, they suffer and, as we know, the pharmaceutical industry It is one of the three or four that more money "generate" in the world and the companies of the "agribusiness" are monopolising control of the world's food. It is understandable that those who have access to this information try to find alternatives.
The scientific problem that underlies this situation is that both industries seem to continue to base their activities on reductionist conceptions of natural phenomena and the competitive and “random” vision of the relationships between the components of life, all of which have already been superseded by so-called "basic research" or non-applied science. Therefore, attacks on these components of life produce serious effects on the body that are not identified as being a consequence of those attacks because their true function is not known. This is why “bolus” genetic manipulations and the use of viruses, transposons and plasmids as “vectors” to introduce foreign “genes” into genomes have unpredictable consequences. For this reason, the "genes" introduced into transgenic living beings produce genomic alterations with unpredictable and uncontrollable consequences and that is why they "escape" from transgenic organisms, producing contamination and irreversible genetic imbalance.
As for the second question, I will try to be shorter. The practice of science is a wonderful activity. For me, and I imagine for most scientists, there is no profession more beautiful or more personally rewarding than to dedicate yourself to the search for knowledge to share with others. And the knowledge about Nature, more profound each day, is showing us a reality that surpasses the fantasies of the most creative mind. A World (perhaps a Universe), in which each and every one of its components is integrated, coordinated in a network that connects the organic world with the inorganic in which all, absolutely all its components have their role. All contribute (I do not say "cooperate" because, as I said before, we have already had an "overdose" of the application of social concepts to Nature) to the balanced maintenance of life, and Nature has its own means to maintain this balance. But everything has its limits…
I believe that this is what must be transmitted to society, and not the messages of "competition", of "arms races", of evolutionary "advantages" and of "survival of the fittest". In this way, Science can be valued by society in a way that it deserves. And we should also explain what Science is and what it is not (yes, Science with a capital S). Because technology is not Science. It is the application, for practical purposes (economic in our society) of scientific knowledge. But if these applications are carried out without having sufficient knowledge, without being clear about what is being done and without controlling the effects of these manipulations, these attacks on Nature can have dangerous and unpredictable consequences.
I don't tire of repeating this in all the places where I have been able to speak and I don't tire of writing it wherever I have been able to write, but in my experience, scientific ideas seem to be better understood if they are written in English. So I am going to resort to the words of Carl Woese in his article "A new Biology for a new Century", published in 2004 in the journal MICROBIOLOGY AND MOLECULAR BIOLOGY:
A society that permits biology to become an engineering discipline, that allows that science to slip into the role of changing the living world without trying to understand it, is a danger to itself. Modern society knows that it desperately needs to learn how to live in harmony with the biosphere. Today more than ever we are in need of a science of biology that helps us to do this, shows the way.
Translation: David Montoute
Entrevista original con el equipo de La Ciencia y sus Demonios:
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