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Miranda Wrongs: Reading Too Much into the Genome

“We meant it for the best.” – Dr. Caron speaking of the Miranda settlers, in Whedon’s Serenity

When the sequence of the human genome was declared essentially complete in 2003, all biologists (except perhaps Craig Venter) heaved a sigh of gladness that the data were all on one website, publicly available, well-annotated and carefully cross-linked. Some may have hoisted a glass of champagne. Then they went back to their benches. They knew, if nobody else did, that the work was just beginning. Having the sequence was the equivalent of sounding out the text of an alphabet whose meaning was still undeciphered. For the linguistically inclined, think of Etruscan.

The media, with a few laudable exceptions, touted this as “we now know how genes work” and many science fiction authors duly incorporated it into their opuses. So did people with plans for improving humanity. Namely, there are initiatives that seriously propose that such attributes as virtue, intelligence, specific physical and mental abilities or, for that matter, a “happy personality” can (and should) be tweaked by selection in utero or engineering of the genes that determine these traits. The usual parties put forth the predictable pro and con arguments, and many articles get published in journals, magazines and blogs.

This is excellent for the career prospects and bank accounts of philosophers, political scientists, biotech entrepreneurs, politicians and would-be prophets. However, biologists know that all this is a parlor game equivalent to determining the number of angels dancing on the top of a pin. The reason for this is simple: there are no genes for virtue, intelligence, happiness or any complex behavioral trait. This becomes obvious by the number of human genes: the final count hovers around 20-25,000, less than twice as many as the number in worms and flies. It’s also obvious by the fact that cloned animals don’t look and act like their prototypes, Cc being the most famous example.

Rainbow, left, nuzzles the ear of her clone "cc", for "carbon copy", on a table at Texas A&M University. (AP) Photo: cbsnews.com/Genes encode catalytic, structural and regulatory proteins and RNAs. They do not encode the nervous system; even less do they encode complex behavior. At the level of the organism, they code for susceptibilities and tendencies — that is, with a few important exceptions, they are probabilistic rather than deterministic. And although many diseases develop from malfunctions of single genes, this does not indicate that single genes are responsible for any complex attribute. Instead they’re the equivalent of screws or belts, whose loss can stop a car but does not make it run.

No reputable biologist suggests that genes are not decisively involved in outcomes. But the constant harping on trait heritability “in spite of environment” is a straw man. Its main prop, the twin studies, is far less robust than commonly presented — especially when we take into account that identical twins often know each other before separation and, even when adopted, are likely to grow up in very similar environments (to say nothing of the data cherry-picking for publication). The nature/nurture debate has been largely resolved by the gene/environment (GxE) interplay model, a non-reductive approximation closer to reality. Genes never work in isolation but as complex, intricately-regulated cooperative networks and they are in constant, dynamic dialogue with the environment — from diet to natal language. That is why second-generation immigrants invariably display the body morphology and disease susceptibilities of their adopted culture, although they have inherited the genes of their natal one.

Furthermore, there’s significant redundancy in the genome. Knockouts of even important single genes in model organisms often have practically no phenotype (or a very subtle one) because related genes take up the slack. The “selfish gene” concept as presented by reductionists of all stripes is arrant nonsense. To stay with the car analogy, it’s the equivalent of a single screw rotating in vacuum by itself. It doth not even a cart make, let alone the universe-spanning starship that is our brain/mind.

Brain DNAAbout half of our genes contribute directly to brain function; the rest do so indirectly, since brain function depends crucially on signal processing and body feedback. This makes the brain/mind a bona fide complex (though knowable) system. This attribute underlines the intrinsic infeasibility of instilling virtue, intelligence or good taste in clothes by changing single genes. If genetic programs were as fixed, simple and one-to-one mapped as reductionists would like, we would have answered most questions about brain function within months after reading the human genome. As a pertinent example, recent work indicates that the six extended genomic regions that were defined by SNP analysis to contribute the most to IQ — itself a population-sorting tool rather than a real indicator of intelligence — influence IQ by a paltry 1%.

The attempts to map complex behaviors for the convenience and justification of social policies began as soon as societies stratified. To list a few recent examples, in the last decades we’ve had the false XYY “aggression” connection, the issue of gay men’s hypothalamus size, and the sloppy and dangerous (but incredibly lucrative) generalizations about brain serotonin and “nurturing” genes. Traditional breeding experiments (cattle, horses, cats, dogs, royal families) have an in-built functional test: the progeny selected in this fashion must be robust enough to be born, survive and reproduce. In the cases where these criteria were flouted, we got such results as deafness, mental instability, and physical fragility, as with Alexei Romanov (the hemophiliac son of Tsar Nicholas II).

There are no genes for virtue, intelligence, happiness or any complex behavioral trait.

I will leave aside the enormous and still largely unmet technical challenge of such implementation, which is light years distant from casual notes that airily prescribe, “just add tetracycline to the inducible vector that carries your gene” or “inject artificial chromosomes or siRNAs.” I play with all these beasties in the lab, and can barely get them to behave in homogeneous cell lines. Because most cognitive problems arise not from huge genomic errors but from small shifts in ratios of “wild-type” (non-mutated) proteins which affect brain architecture before or after birth, approximate engineering solutions will be death sentences. Moreover, the proposals usually advocate that such changes be done in somatic cells, not the germ line (which would make them permanent). This means intervention during fetal development or even later — a far more difficult undertaking than germline alteration. The individual fine-tuning required for this in turn brings up differential resource access (and no, I don’t believe that nanotech will give us unlimited resources).

Let’s now discuss the improvement touted in “enhancement” of any complex trait. All organisms are jury-rigged across scales: that is, the decisive criterion for an adaptive change (from a hemoglobin variant to a hip-bone angle) is function, rather than elegance.  Many details are accidental outcomes of an initial chance configuration — the literally inverted organization of the vertebrate eye is a prime example. Optimality is entirely context-dependent. If an organism or function is perfected for one set of circumstances, it immediately becomes suboptimal for all others. That is the reason why gene alleles for cystic fibrosis and sickle cell anemia persisted: they conferred heterozygotic resistance to cholera and malaria, respectively. Even if it were possible to instill virtue or musicality (or even the inclination for them), fixing them would decrease individual and collective fitness. Furthermore, the desired state for all complex behaviors is fluid and relative.

DNA Nucleus Organic CellsThe concept that pressing the button of a single gene can change any complex behavior is entirely unsupported by biological evidence at any scale: genomic, molecular, cellular, organismic. Because interactions between gene products are complex, dynamic and give rise to pleiotropic effects, such intervention can cause significant harm even if implemented with full knowledge of genomic interactions (which at this point is no even partially available). It is far more feasible to correct an error than to “enhance” an already functioning brain. Unlike a car or a computer, brain hardware and software are inextricably intertwined and cannot be decoupled or deactivated during modification (see: Why Our Brains Will Never Live in the Matrix)

If such a scenario is optional, it will introduce extreme de facto or de jure inequalities. If it is mandatory, beyond the obvious fact that it will require massive coercion, it will also result in the equivalent of monocultures, which is the surest way to extinction regardless of how resourceful or dominant a particular species is. And no matter how benevolent the motives of the proponents of such schemes are, all utopian implementations, without exception, degenerate into slaughterhouses and concentration camps.

The proposals to augment “virtue” or “intelligence” fall solidly into the linear progress model advanced by monotheistic religions, which takes for granted that humans are in a fallen state and need to achieve an idealized perfection. For the religiously orthodox, this exemplar is a god; for the transhumanists, it’s often a post-singularity AI. In reality, humans are a work in continuous evolution both biologically and culturally and will almost certainly become extinct if they enter any type of stasis, no matter how “perfect.”

But higher level arguments aside, the foundation stone of all such discussions remains unaltered and unalterable: any proposal to modulate complex traits by changing single genes is like preparing a Mars expedition based on the Ptolemaic view of the universe.

 

27 Comments


  1. > It is far more feasible to correct an error than to “enhance” an already functioning brain.

    I would like to submit that everyone’s genome is riddled with non-lethal errors. I think it follows that if we corrected a large part of these, the result would be indistinguishable from “enhancement”.

  2. > Namely, there are initiatives that seriously propose
    > that such attributes as virtue, intelligence, specific
    > physical and mental abilities or, for that matter,
    > a “happy personality” can (and should) be tweaked
    > by selection in utero or engineering of the genes that
    > determine these traits.

    While in general your argument is correct, please note that we are already tweaking physical and mental abilities with some success. Physically, with blood pressure, lipid, and many other medications which have had substantial impact on mortality. Mentally, with psychoactive drugs that have all but eliminated the horrible psychiatric institutions of the past and allow millions of people to lead normal lives that would otherwise be unable to care for themselves. Antidepressants are quite effective at tweaking a “happy personality”, to speak to your examples.

    Tweaking with genes is no worse than tweaking with drugs regarding the problems you point out, but has a much more general applicability. Drugs are “accidentally” effective, because they happen to interact with particular cogs in the biological machinery. Genes allow you to target those cogs much more precisely.

  3. Good article. Single gene manipulation/modification or replacement normally has bad effects, unless using therapy to fix a known defect or making a recessive become a dominant through therapy. When I talk to people about genetic memory, most think of concuss memory and not genetic traits type. though I think some day we will be able to enhance functions through complex combinations of gene modifications and chemical expressions. I.E. not just tinkering with 1 part like mitochondrial DNA to express higher levels of energy output or new chemical combinations, or even new or modified methyl ethyl expressive traits that reflect or react to there surroundings. As for intelligence or virtue, personally I think that comes more from surroundings and development over time. I.E. the sandbox and expansive rule sets, similar to the type of A.I. structuring and growth, but more localized. As far as human modifications, Don’t rule it out. Look at plant or insect modifications done with DNA loops from other species spliced into them. I.E. G.M.O.’s. Corn that grows plastics, and plants with non plant genes for a specific effect or outcome. Weather it’s done through known mutagens, or spliced, or chemically repressed or expressed, or even evolved threw excess and habitat and such. The possibility’s are there, but most likely are still alien to most people as to how all the right pieces fit together for the desired outcome. Oh well just my thoughts and 2 cent’s. And don’t rule it out, as chemical gene expression is happiness and sadness and such. And a greater brain mass or such is useless without knowledge to fill it. :)
    Patient 0.1357

  4. In this context, “error” means decrease in function in the broadest sense. If it doesn’t affect function, how do you define it and what will you be correcting? For one, it would be the equivalent of NASA’s expensive nails, except worse — you could end up hurting or even killing people.

  5. The fallacies in your article are quite obvious. From a discussion the pitfalls of a naive conception of genetic engineering, where you make a valid point, you jump to generalities about human enhancement. Simply put, you equate enhancement with gene manipulation. That may or may not be the result an underlying assumption that a single-minded gene-centered view of life is the correct one. And, of course, for some characteristics of life, that is a perfectly reasonable assumption. When talking about intelligence, however, the neurocomputational and neurochemical levels of abstraction are bound to be more helpful. And at least in the case of the latter, there have been many results of enhancement, even though a temporally restricted one: the simplest example is amphetamines.

    The worst kind of skepticism is the one that comes from being semi-educated on a subject; skepticism that comes from the uneducated can easily be dismissed, and skepticism that comes from the educated is greatly appreciated. But this kind of ill-informed skepticism is a tricky one to see through.

  6. Briefly, the gathering evidence on antidepressants is that they’re no better than placebos (which can be very effective, but nowhere near the fine-tuning pharma claims for them). And the topic here is genes, not drugs. If you want to discuss higher-order structures, that would be a different article.

  7. Genes can be “accidentally” effective too; there is hardly less non-linearity and unpredictability associated with one than is associated with the other.

  8. I have seen the proposals I discuss, and they propose exactly what I say. And I’m as educated on the subject as you can possibly be. I have a PhD in Molecular Biology and do genomic regulation research. Whereas your credentials are…? For that matter, your name is…?

  9. Drugs are NOT higher-order than genes, they work in the same haphazard, individual-part way that you have rightly ascribed to genes.

    And if you roundly deny the effectiveness of psychotropics, you are doing the same to psychiatry that you accuse others of doing to biology.

  10. Antidepressants are but a small fraction of the possible neurochemical modifications available. What about amphetamines, including the well-known study-drug Adderall, or even less effective stimulants such as caffeine? Especially in the case of the former, you can hardly argue against its effectiveness. Even psychedelic phenethylamines or tryptamines are arguably a form of enhancement, since they allow us to access altered mental states that have proven to be quite beneficial to a large population, especially artists. Et cetera.

  11. Errors decrease function. You can correct errors. You get increased function. I think you have said the first two yourself, how can you deny the third, which clearly follows?

  12. Your article was informative and insightful until you decided to go for hasty generalizations and try to come to conclusions regarding the entirety of the human endeavor to improve the human condition. It is arbitrary and unjustified claims like the following that greatly devalue your article:

    “It is far more feasible to correct an error than to “enhance” an already functioning brain. Unlike a car or a computer, brain hardware and software are inextricably intertwined and cannot be decoupled or deactivated during modification.”

    As you say in a response to a comment, “the topic here is genes, not drugs.” Even if your intention was to talk exclusively about genetic modification, you would agree that the reader would assume that in general, it is not very feasible to “enhance an already functioning brain” in general. You do not seem to try to make it known that genetic modification is but a grain of sand in a sea of possibilities of human modification.

    Of course, that is clearly a minor issue. But what comes later is unsubstantiated, ad hominem (by the obviously derogatory comparison of transhumanist thinking to monotheistic religions) attacks to a way of thinking that are completely unrelated to everything you said earlier.

    “The proposals to augment “virtue” or “intelligence” fall solidly into the linear progress model advanced by monotheistic religions, which takes for granted that humans are in a fallen state and need to achieve an idealized perfection.”

    If you wish to assert that they are actually related, then I have no choice but to answer that you are making an induction out of nowhere by criticizing a way of thinking (i.e. human enhancement) because one particular way to approach it (i.e. genetic modification) is incorrect or filled with naive attempts. If you think that other ways of approaching enhancement are incorrect or naive, you should have made an attempt to indicate why.

    I did not, at any point, cast any doubt to information I am not in the position to analyze or dispute in my original comment. I only criticized the philosophical connection you made between your scientific analysis (which, I repeat, I did not criticize) and a general system of thought.

    And maybe your credentials are part of the problem. Your field of study is not the only one in which enhancement can occur. Overspecialization with no regard to alternative ways of thinking is a form of semi-education, and certainly not a rare one. When you lack the philosophical motivation or ability to clearly see the bigger picture, the field that you are studying becomes larger and larger in your mind until your vision is completely tunneled.

    I would appreciate it if next time you answered directly to my criticisms instead of indulging in the academic game of “credentials.” I’m not fighting against you, I’m fighting against your ideas. Even if I did, my point of contention was not related to your academic/research subject, but rather your conclusions, which did not have a scientific nature. So your comment was completely irrelevant, and, dare I say, immature. I do not think I deserved such a response.

  13. Yes there is. It is one more level of indirection. Drugs are designed to interfere with particular targets, which are almost always proteins. For example, in the case of the most popular antidepressants, the serotonin reuptake inhibitor. With both drugs and genes, you first have to find and understand your target. If you have a way to modify the gene, you are then done. If you want a drug, on the other hand, you now have to now find a chemical that affects the target, and at the same time make sure that no other targets are affected. This is difficult, time-consuming, expensive, and not always possible.

    This is why so much excitement went to antisense, siRNA, and gene therapy, all of which promise to remove this “small molecule” part of the process. So far, with little to show for, but I think success will come with time and persistence.

  14. On the contrary, you brought up credentials first, and directly so: “The worst kind of skepticism is the one that comes from being semi-educated on a subject.”

    For the rest, I don’t debate anonymous hecklers, especially ones who are responding to different issues than those that I discuss.

  15. As I already said, if this article were about psychotropic drugs, I’d discuss them. It’s not, so I won’t — beyond saying that I never denied their effectiveness. Except that they’re not effective in the way their proponents (like to) think.

  16. “Non-lethal errors” are identical to “variant alleles”. This takes us right back to the dead-ending by optimization, which works only in a single, unchanging context.

  17. If you interpreted that as a reference to credentials, I can only answer with a quote: “I have never let my schooling interfere with my education.” — Mark Twain

    This is probably my last visit to this site. After an unashamed advertisement in an article form comes an ill-informed, philosophically-naive academician who employs credentials and the utterly irrelevant concept of anonymity to convince instead of arguments. Transhumanism deserves better sources of information than this.

  18. You are being evasive. Drugs are relevant here because they act on individual proteins, just like genetic engineering. Given that, everything you said about the difficulties of genetic engineering applies to drugs as well, and more so because of the additional problem of small molecule selection. The point is that once you find a practical way of targeted mutagenesis (somatic or germ-line), you can do a lot more tweaking than you allow in your article, and drugs prove that.

    You have a better point with intelligence, which is much less tractable than mood adjustment, pharmaceutically or genetically. Happiness, however, which you brought up, is clearly subject to pharmaceutical, and thus also genetic, intervention despite our limited biological understanding of it.

    Along with a whole lot of other traits that are often characterized as “complex”. Height, for example, is known as a typical complex trait, with no single genetic variant accounting for more than a percent or so of variation. Nevertheless, tweaking HGH or the HGH receptor, whether by direct injection, drugs or genetic engineering, will provide a substantial amount of control over it.

  19. There, now, don’t get pouty because you feel that I insulted your transhumorism. Despite your vaunted self-professed philosophical sophistication, you apparently don’t recognize ad hominem when you practice it… or is it because you’re practicing ad feminem?

    If you dislike expertise so much, by all means have the next person you meet on the street repair your car — or take out your wisdom teeth. As for me, I will happily continue to read Homer and Nietzsche in the original, sing in four languages, and publish fiction and non-fiction works with major publishers, in addition to my research.

  20. I know you work in biotech, so I’ll be brief. You and I both know that most drugs affect more than one target and that targeted delivery (to specific organs, brain compartments, cell types) and correctly regulated, context-responsive expression is the Holy Grail for both drugs and gene knock-ins. So it’s unclear what you’re disagreeing with, beyond wanting to nitpick.

    Happiness is far more dependent on such parameters as one’s fit into prevailing cultural values, status in family and work groups and the security of the necessities of life — up and down the hierarchy of needs, which includes the lonely poor little rich kid. You can give Prozac to Afghan women, so that they don’t notice (or at least are too zonked to care) when the Taliban throw acid on their faces as they try to attend school. But I suspect that less toxic mindsets and better education would do a lot more for their happiness, both short- and long-term.

  21. Sorry to bust your bubble but “Researchers led by scientists at the University of Utah’s Brain Institute have discovered that a single gene (STX1A) may account for more than 15% of the variation in IQ among those people with Willliams Syndrome.” “Scientists hope that the strong correlation between STX1A and intelligence may provide insight into the general population as well.” excerpts taken this article http://singularityhub.com/2010/04/22/gene-for-intelligence-revealed-by-studying-williams-syndrome/

  22. And sorry to bust yours, but I already replied to this in another thread on H+ magazine, at RU’s request. I’m reproducing my reply here, slightly expanded:

    “Actually, the report reinforces my point that we can easily find a cracked screw that causes a car to stall, but doesn’t make the car run by its lonesome. Korenberg’s group studied people who have Williams syndrome, which affects neuronal transmission and hence brain function. The gene they zeroed in on, STX1A (syntaxin 1A) belongs to a family — as most human genes do — that codes for docking proteins.

    So what they did is identify one gene whose malfunction may cause Williams syndrome, just as the 50% overexpression dual-activity kinase encoded by DYRK1A causes much of the Down syndrome cognitive problems but is not a single-entry point to high intelligence (however you define it). The statement that the malfunction “may account for 15% of the variation in IQ among those with Williams syndrome” means that there are at least seven other genes involved, whose malfunction can also result in the syndrome.

    The article is not yet available on PubMed, so I won’t be able to judge its substance until I see it. Much of the reporting in the link is standard PR to boost the university’s profile and donations (and, frankly, good for them!). Also, publication in PLoS One means the study is not as groundbreaking as the PR tries to imply.”

    Next time, read more than PR before thinking that you’ve burst any bubbles beyond those in the Singularity Hub.

  23. A truly enjoyable piece and an important counterpoint to so much of the simplistic science boosterism and reductionism amongst the h+ crowd and Singularity enthusiasts. This is also a nice rejoinder to the rather terrible piece on Darwinian Psychology a while back. I find it ironic that people, like some transhumanists, who think we humans are so wonderful and complex that we will be able to supercede our own biological limits are so willing to accept that we are so simple that all it will take will be a next generation Apple gadget and a storage device with our own genome in it. None of which is to suggest that the advances taking place right now in biology, nanotech or computing aren’t phenomenal. But it just ain’t that simple. The mind is not simply a good calculator with eyes attached – it is an unbelievably plastic system that juggles, interprets and responds to an enormous amount of ongoing data at both a conscious and unconscious level. The same applies, as you so eloquently describe, as far as genes are concerned and belief in the panacea of genetic engineering to raise your intelligence or increase your happiness are delusional. (In fact, I’d suggest that trying to make yourself happy independent of your social conditions would only be possible by lowering your intelligence to the point where you were too stupid to notice that your life sucked).
    My only contention with your article – just so no one suspects I’m the president of your fan club – is ascribing the model of linear progress to monotheistic religion. Pre-modern monotheism was actually much more cyclical in outlook. I think the present incarnations of religion, as well as biological reductionists of various sorts, are more indebted to the Enlightenment’s notion of unending linear progress and the rise of positivism, which did away with the role of human agency in any coherent sense. The biological reductionists are the heirs of people like Malthus and the scientific racists (no, I’m not saying they are all racists) who needed to find ways to justify the seeming contradiction between the increasingly held views that it is “self-evident that all men are created equal” and yet Africans were kept in chains and women were kept in the home. Without the old religious justifications of the feudal estates and hierarchies of angels to use as props, science and rationalism became the new (now rather old) way to explain why inequality was not only necessary but good. As you demonstrate, it is bad – and dangerous – science and worse social theory. The sooner that humans focus on eliminating social inequality and embracing biological and scientific complexity the more rapid will be our advances as a species.

  24. Shawn, you hit many bulls-eyes with your comments.

    Frankly, anyone who uses “Darwinian psychology” (whatever the hell that means) to justify anything is either ignorant of basic biological realities or wants to retain unexamined, unquestioned privileges. I’ve actually had futurologist wannabees issue such statements as “alpha males have rape genes” and “female brains are wired for coyness” — very funny, if it weren’t sad, given that such people do exert influence.

    I gave a response very similar to yours concerning happiness to a comment earlier in the thread. I agree that the concept of perfectibility solidified in Western thought with the advent of Enlightenment (and the stories of humanity’s fall are far older than the garden of Eden fable). Still, monotheistic religions are overall more “linear” than other variations.

    Science is a unique human endeavor in that it’s self-correcting if practiced properly. But pernicious concepts and practices wrapped in the mantle of scientific respectability (but lacking any grounding in real science) have often been used to reinforce the status quo.

  25. so what am i gay or is it incest if i bang my female/male clone?

  26. Homosexual, yes, since your clone will share your gender. Incest — that depends on many parameters, some biological, some cultural. And for all you know, s/he may bang you.

  27. “there are no genes for virtue, intelligence, happiness or any complex behavioral trait”
    OK, maybe the idea of manipulating single genes to alter complex traits is flawed. But are you saying that even with an implausible degree of knowledge, manipulating the genome to significantly enhance these characteristics is impossible? If not, then your criticism seems rather weak, as I don’t think most of these proposals focus on changing single genes anyway. Though I am probably missing something here. Care to clarify?