Can Human Evolution Be Controlled?

BQO-Hurlbut-990x580[Wikimedia] Bill Sanderson, "A man entwined in the coils of DNA" (scraperboard drawing, 1990), copyright Wellcome Images, available under CC BY 4.0

Earlier this month, an international initiative convened by the national science academies of the United States, China, and the United Kingdom released a major report on the implications of new “gene-editing” technologies, most notably the recently developed tool CRISPR/Cas9. The report was broadly optimistic about the scientific and technological potential of tools like CRISPR/Cas9, which has been employed in labs around the world, generated thousands of scientific publications, and attracted over a billion dollars in venture capital for private companies exploring its medical and commercial applications.

These gene-editing techniques may transform our world as profoundly as many of the greatest scientific discoveries and technological innovations of the past — like electricity, synthetic chemistry, and nuclear physics. CRISPR/Cas9 could provide urgent and uncontroversial progress in biomedical science, agriculture, and environmental ecology. Indeed, the power and depth of operation of these new tools is delivering previously unimagined possibilities for reworking or redeploying natural biological processes — some with startling and disquieting implications. Proposals by serious and well-respected scientists include projects of broad ecological engineering, de-extinction of human ancestral species, a biotechnological “cure” for aging, and guided evolution of the human future.

The questions raised by such projects go beyond issues of individual rights and social responsibilities to considerations of the very source and significance of the natural world, its integrated and interdependent processes, and the way these provide the foundational frame for the physical, psychological, and spiritual meaning of human life.

Cures — and Control?
With the CRISPR revolution, researchers are reporting dramatic gene-editing advances in mouse models in a wide range of genetic disorders, including sickle-cell anemia, Duchenne muscular dystrophy, and Fanconi anemia. And an article published in late 2016 in the journal Nature reported that a Chinese group has become the first to treat a human being — a lung-cancer patient — with cells that contain genes edited using the CRISPR/Cas 9 technique.

The dramatic potential of such therapies is immediately obvious; for the first time we will have the power to treat hundreds, perhaps thousands, of diseases and conditions for which we currently have no effective therapy. It is important to recognize that in many cases it may not be necessary to alter all the cells in an organ, just 20 or 30 percent may be adequate to restore natural functioning. It is also obvious that, in certain cases, the earlier the genetic interventions can be made, the better the treatment outcome will be in preventing disease onset and allowing normal development. This has reawakened the long-held hope that we might one day be able to make targeted DNA modifications directly at the level of the human gametes (sperm and egg) or early embryos, and thereby remove a genetic disease once and for all from a family lineage.

But this, in turn, raises challenging questions about what degree of acceptable risk and what types of conditions should count as worthy targets of our interventions. Are albinism and dyslexia conditions we should treat? And what about parental preference for hair and eye color or taller stature? Red hair, for example, is caused by a single gene. Most conditions we would care about — intelligence, beauty, longevity — result from interaction among many genes and would not be easy to target, but as we learn more about the genetic basis of depression, autism, and Parkinson’s disease, we may be tempted to develop preemptive germline interventions.

Harvard geneticist George Church has compiled a list of “rare protective gene variants of large impact” that exist naturally in the human genepool — but only in a few people. These include variants correlated with extra-strong bones; lean muscles; lower risks of coronary artery disease, cancer, and diabetes; and greater resistance to viruses — all of which might improve general health if more common.

In response to such suggestions, developmental biologist Stuart Newman warns:

The genetic design of future offspring, even with the limited objective of making these future children more “normal,” will open the door to attempts to pick and choose other characteristics, because definitions of normality will vary, as will access to technology and willingness to take risks with future lives.

Remaking Humanity
Yet, some argue that it is human nature and human destiny to improve ourselves even at the most fundamental level of our genes. These include the “transhumanists,” an international intellectual and cultural movement advocating technologically mediated enhancement of human intellectual, physical and psychological capacities. Their logo is h+ — that is, “humanity plus,” for improved humans.

Transhumanists argue that our advancing technologies offer us the opportunity to escape the constraints and cruelties of an amoral evolutionary process, to lift humanity to its next level of personal and social flourishing as genetically enhanced human/machine-hybrid “posthumans.”

On a less dramatic level, many point to the steady increase in medical interventions for purposes “beyond therapy.” The traditional role of medicine has been to cure disease and alleviate suffering; to restore and sustain the patient to a natural level of functioning and well-being. The medical arts were in the service of a wider reverence and respect for the order of the created world. This idea was put succinctly by the Roman physician Galen (in his commentaries on Hippocrates) when he said, “the physician is only nature’s assistant.” But now, with the powers of our advancing biotechnology, there is a new paradigm, one of liberation: technological transformation in the quest for happiness and human perfection.

Grounded in the widespread practice and general acceptance of cosmetic surgery, slowly but steadily the scope and purposes of medicine are being extended along the gradient of our appetites and ambitions to encompass dimensions of life not previously considered matters of health but natural human variation or limitation.

From Rogaine for baldness, growth hormone for shortness, to birth control pills, and Viagra — and more recently Provigil (a drug that allows prolonged periods of wakefulness) and Seasonale (a technological bypass to the monthly periodicity of the natural menstrual cycle) — in all these ways we have altered and revised the given frame of nature. Increasingly, we have come to expect from medicine not just freedom from disease, but freedom from distress, struggle and even the constraints of a natural life process — from all that is unattractive, imperfect or just inconvenient.

As we gain increasing control over the very molecular basis of life, we need to pause to consider carefully how we should proceed. Within both the scientific community and the general public, there is wide recognition that our new gene-editing tools are a “threshold technology,” an opportunity for us to re-envision and re-order our place and purpose within the natural world. The issues involved go beyond biology — our whole sense of personal and social destiny may be hanging in the balance.

The environmental thinker Aldo Leopold offered a maxim that could be useful in this context:

If the biota, in the course of aeons, has built something we like but do not understand, then who but a fool would discard seemingly useless parts? To keep every cog and wheel is the first precaution of intelligent tinkering.

There is much that we do not yet understand in our biology, including the causes and nature of traits that would seem to impose struggles and constraints on our aspirations. We must not be so foolish or arrogant as to ignore the natural foundations that underlie our human freedom. And just as the human body has been assembled into an organic whole, our civilization is assembled out of cultural, philosophical, and spiritual principles and traditions that should not be casually discarded. The very future of humanity may depend upon this.

Discussion Questions:

1. What difference is there between changes to humanity through natural processes of evolution and directed technological methods like CRISPR/Cas9?

2. What would you want to change in the human genome? What would you want never to be changed?

3. Can we draw reliable distinctions between genetic “therapy” and “enhancement”?

4. Is the essence of humanity contained in the human genome, and would it be changed in the genome were significantly edited? Or is it something that cannot be edited?

Discussion Summary

In our discussion, readers raised a number of interesting new questions and delved deeper into many of those already considered in my essay, especially regarding the feasibility and desirability of gene editing technologies and the underlying implications for human nature and biology. A few key points I noted in my responses:

1. Altering the natural form of a single gene will have many affects, and, apart from genetic diseases, rarely will it have a decisive impact on something of central significance in an individual’s life.

2. The open and indeterminate aspect of human nature is close to the core of what makes us a distinctive species. Yet, this extraordinary capacity for freedom is built on a highly specialized and fragile frame of biological features. In our quest for human perfection, it is this foundation and frame that we must be careful not to destroy.

3. It may be quite disruptive if our discernment and selection begins to delve to the genetic depths of many human characteristics, especially if we turn those discernments into active programs of “improvement” at every level of biology and behavior.

20 Responses

  1. 1. Changes via natural evolution took place over ten-thousands and millions of years, prior to the dawn of modern technology and understanding. It yielded a single species (with all its diversity). Genetic modification of the human species can potentially take place now over a few generations and poses a threat to the given unity of our species.

    2. I think we should repair genetic damage which causes disease.

    3. Practically every argument that it is impossible to distinguish therapy from modification begins by making that distinction. It’s dishonest; we do know the difference. Formal definitions can be worked out to codify how to decide particular cases. If there are borderline cases and we get it wrong sometimes, that’s OK. We can stop the wholesale rush into modification of the human species.

    4. Humanity is the living human species and cannot be reduced to any “essence.” But the genome is an important part of humanity. If it were substantially modified, it, and the creatures it gave rise to, would not be entirely human. This we should not do. We are human, and we should use our technology to preserve the human species, not to modify it out of existence.

    • William B. Hurlbut William B. Hurlbut says:

      You are certainly right about taking a long-range view of these matters. Diversity is one of the marks of a robust species gene pool, and we may not fully appreciate the importance of natural variations within our genome. There is an old saying that the human species is “packed for all kinds of weather.” Clearly, any efforts to re-tailor the genetic traits of our children could fall into the ‘flavor of the month’ dilemma — fashioning them for particular purpose or specific conditions that may change even within a generation or two.

      In any case, it is not clear that projects to produce ‘designer babies’ are grounded in a realistic understanding of genetics. Two basic principles need to be kept in mind–pleiotropy and polygenic inheritance.

      Pleiotropy means that most genes do many things in human development and in ongoing body processes. Genes code for proteins, and these proteins are the basic building materials for multiple aspects of human development and maintenance. This is why single-gene genetic diseases are usually expressed as ‘syndromes,’ a cluster of anatomical and physiological disorders. So, for example, a single mutation may be associated with short stature, heart problems, and lower general intelligence. And, even in healthy development, if we alter a single gene hoping to enhance some specific trait, it is likely that we will get effects elsewhere in development that we didn’t anticipate or desire.

      Polygenic inheritance means that most traits we care about — intelligence, longevity, beauty (including height and eye color) — are influenced by many genes. For complex traits such as intelligence, this may involve hundreds of genes, each of which has only a relatively small effect. So, to engineer desired outcomes may require much more extensive intervention than most people imagine.

      So, genes are a little like paints on an artist’s palate. Rarely is a primary color applied directly to the canvas. Rather, the basic pigments are mixed together to produce a vast range of subtle hues, and each primary color is used in many different ways. So, altering the natural form of a single gene will have many affects, and, apart from genetic diseases, rarely will it have a decisive impact on something of central significance in an individual’s life.

  2. Chris says:

    All great points. There’s also the capitalist/socialist/meritocracy considerations. One way or another, certain group advantages/disadvantages will emerge and so will resentment. We aren’t just talking about socialists redistributing money or the affluent buying organic food. We’re talking about access to different patterns of evolution.

    • William B. Hurlbut William B. Hurlbut says:

      Yes, and the resentments might be from unexpected sources. When I give talks on this subject I am frequently asked if this will further exaggerate the social and financial inequalities of society — won’t the children of the rich be the lucky ones?

      In fact, at least for the first few decades of such genetic interventions in the quest for human enhancement, it may be the children of the poor who will be the ‘fortunate’ ones. If society does move toward allowing such projects as an extension of arguments based on ‘reproductive liberty,’ the children of poor families may escape the consequences of imprudent human experimentation.

      Some, including Nobel Laureate James Watson, have, according to reports, suggested we could simply dispatch (put to death) newborn children with evident mistakes that result from such scientific projects. Of course, if the horror of state sponsored programs of eugenics reemerges, there is no telling what levels of tragedy (and resentment) might emerge.

  3. Trenty says:

    Dr. Hurlbut,

    Given the messiness of the whole species concept in general, along with the fact that the “species” is not a being that can experience joy or suffering or anything else, does it really make much sense to worry about the future of the human species? Shouldn’t we worry about the future of human beings and our descendants, and do our best to provide them with the conditions under which they can live healthy, flourishing lives rather than worrying about whether our descendants will be “human”?

    • William B. Hurlbut William B. Hurlbut says:

      Trenty,

      That’s an interesting comment, especially considering that so many among us are deeply concerned about the rate of species extinction on our besieged planet. Clearly, when it comes to human being, we are primarily concerned with the characteristics that give individual humans the distinctive strengths of our species.

      I am co-leader at Stanford on an interdisciplinary faculty project entitled “The Boundaries of Humanity: Humans, Animals, and Machines in the Age of Biotechnology.” A major part of this project is an effort to discern and clarify exactly what it is that constitutes human uniqueness among the species of the living world, and how those distinctive characteristics differ from what can be designed into the machines we build (specifically, computers and robots).

      Many of the features that seem to define human nature are increasingly being recognized in other species (self-awareness, tool use, horizontal transmission of culture, etc.) or emulated in our machines (computation, planning, pattern recognition, etc.). In light of these similarities, some people deemphasize our distinction by labeling us ‘just another ordinary animal species’ or just a complex machine. Yet, even if our distinctions are just an intensification of characteristics prefigured in other animals, there is a sense in which a quantitative difference can be a qualitative difference. And even if some human cognitive capacities can be programmed into machines, that does not mean that they are the same as human thought.

      When you speak of healthy and flourishing human being, you are probably thinking of purposeful creativity, satisfying personal relationships, and probably some notion of transcendent moral and spiritual meaning. These characteristics of human beings are so variably expressed and so deeply personal that there is a sense in which every human person could almost be described as an individual species.

      It is this open and indeterminate aspect of human nature that is close to the core of what makes us a distinctive species. Yet, this extraordinary capacity for freedom is built on a highly specialized and fragile frame of biological features. In our quest for human perfection, it is this foundation and frame that we must be careful not to destroy.

  4. Jenn says:

    Does it make a difference whether gene edits are heritable or not? If the changes are good for the individual, wouldn’t they be good for his descendants? And if they’re bad for his descendants, wouldn’t they also be bad for the individual?

    • William B. Hurlbut William B. Hurlbut says:

      Jenn,

      Every human being (except, perhaps, identical twins and triplets, etc.) has a unique combination of inherited genetic characteristics. With the reshuffling and recombination of genes that results from sexual reproduction, some traits and disorders that appear in one generation will not appear in the next. This is because gene expression is affected by the other genes that are present, as well as diverse environmental influence.

      So, any effort to improve the individual through germ line interventions (in the sperm and/or egg) would have unpredictable results. And even when such projects were successful in one generation, they might not be in the next. Moreover, there are studies that show that some people carry genes that usually are associated with a disease, yet have no symptoms. And, even identical twins often have different expressions of inherited diseases.

      Considering the risks and uncertainties of germ line alterations, and the social dangers of opening up programs of genetic predesign by parental preference, it is probably wiser to treat the individual patient at the level of somatic cells (body cells). As our scientific knowledge increases, we may be able to detect and treat serious disorders even in the womb.

  5. Can Human Evolution Be Controlled? Sure, we do it all the time. Every time we choose a mate, every time our species favors blue eyes, or black hair, or living in a cold/warm/temperate climate. But intentionally?  Sure, we do that all the time too.

    • William B. Hurlbut William B. Hurlbut says:

      Yes, that’s true — at a certain level. Darwin recognized this and labeled it “sex-selection.” There is quite a lot of evidence that this kind of “genetic choice” is operating in a wide range of species. Such discernment in the service of the preservation and intensification of a species’ strengths is a natural part of its basic biology.

      However, it is important to recognize that only certain features of form and function are selected for by such natural behavioral inclinations. These include evidence of basic health, immune status, and even evidence of good parenting. And, within a given species, there is a delicate balance of natural discernment and what is selected. Some believe that bright peacock tails, huge antlers, and other such exaggerated features may represent a kind of “runaway” evolution, where the advantages of such characteristic are in a delicate (and sometimes deleterious) balance with their selection.

      Human beings, in expressing their attractions, also sometimes select for features of biological significance. We too, are driven by our natural desires and disgusts. But so far, our powers are pretty much limited to general features that are evident through natural observation. It may be quite another thing, and potentially disruptive, if our discernment and selection begins to delve to the genetic depths of many human characteristics, especially if we turn those discernments into active programs of “improvement” at every level of biology and behavior. One wonders what kind of “runaway” evolution we might conjure for ourselves!

  6. Karl Hicks says:

    You mentioned a Chinese study that involved treating an adult cancer patient with CRISPR. But I thought it could only be used for eggs and sperm cells. I could understand “editing” the DNA of one cell (sperm or egg) or even a few cells (in an embryo), but how could you possibly “edit” the DNA of the millions/billions of cells causing a problem like cancer in an adult? How could you target the treatment at the problem? That doesn’t make sense to me.

    • William B. Hurlbut William B. Hurlbut says:

      Although there are numerous gene editing studies currently being conducted on human gametes and human embryos, at this point they are research projects, not directly intended as clinical interventions. Even among those who favor germ line therapies (in egg and/or sperm or early embryos), there is wide recognition that the state of our knowledge is inadequate for such applications on the clinical level.

      At the same time, however, there are many projects underway aiming directly at clinical applications through alteration of somatic cells (later body cells). The easiest form of such therapies will probably be direct gene editing on various kinds of blood cells. These can be easily obtained, altered and multiplied in laboratory culture, and re-injected into the patient. Just last week scientists in England reported encouraging results of gene therapy for Sickle Cell Anemia. This inherited blood disease affects hemoglobin, the major molecule in red blood cells. By genetically altering the patient’s blood stem cells, they were able to return them to the patient where they reestablished their natural niche in the bone marrow and continuously churned out normal blood cells.

      Similar projects are being conducted on other types of blood cells — including circulating immune cells that have been altered to more effectively target cancer cells. And, scientists are working with other types of body cells as well. There is encouraging progress, at least in mouse models, altering muscle cells to treat Duchenne’s Muscular Dystrophy.

      You are right that treating disease at later stages comes with the challenge of altering millions and maybe billions of cells. However, where there are tissue-specific stem cells that can generate many new cells, this is more feasible. And, even for difficult to reach or fragile organs, there are a range of vectors (delivery vehicles) for getting the gene editing mechanisms (including CRISPR/Cas9) directly into the cells. These include specially tailored viruses which can be targeted to specific cell types such as liver, pancreas, and even regions of the brain. And, it is important to realize that even the alteration of some fraction (maybe 20-30%) of the cells of an organ or system may be enough for effective therapy of some disorders.

      Although these clinical applications are still at an early stage of development, they hold the promise of dramatic new treatments and cures within the next several decades, even without germ line interventions.

  7. Marshall K. says:

    Since almost all of our knowledge of genetics comes from mere correlations of genes to phenotypes, is real enhancement (and especially post-human enhancement) really possible? That is, the only thing we know about genes and intelligence is (at best) that some genes are associated with intelligence, but we know very little or nothing about what makes particular genes contribute to the trait. So (at best) we would be able to edit the genome of a person to contain more genes that we know to be associated with intelligence, we wouldn’t be able to design new genes that would confer anything unprecedented to intelligence. (The same would seem to go for other traits as well.)

    • William B. Hurlbut William B. Hurlbut says:

      Marshall, you are certainly right in your overall point that most of our knowledge is based on correlations (a gene seems somehow associated with a trait) not mechanism of action (how the gene affects the trait). You are also right that most things we would want to “improve” are very complicated, involving many gene interactions and environmental impacts that we barely understand.

      Having said that, scientists have identified some genes that seem to play a major role in promoting desirable phenotypes. George Church at Harvard is keeping a list and if you do a search you can see that he includes more than a dozen alleles (variations in a gene sequence) that appear to be beneficial but somewhat rare in the human species. These include alleles that favorably affect bone strength, immunity, and resistance to cancer, etc.

      This raises an interesting and important question: Why are these alleles not already more common? The answer could be because they are recent mutations and there has not been adequate selective pressure to increase their frequency in the human gene pool. Or, it is possible that they affect more than the specific desirable trait and therefore carry negative affects when in combination with other common gene variations or environmental conditions.

      In any case, we are a long way from knowing enough for projects aimed at “post-human” enhancements!

  8. Johnny_Wallach says:

    Thank you. I have a question: Aren’t most of the conditions that might be modified by gene-editing (that is, conditions affected by a single gene or a small number of genes) either diseases that are worth preventing (like cystic fibrosis) or unimportant traits like hair color (at least in the case of red hair)? Are there really any traits people might want to “enhance” that are determined by single genes or small numbers of genes?

    • William B. Hurlbut William B. Hurlbut says:

      Johnny

      Yes, your point is right. I pretty much addressed this in my previous answer, but let me add a few additional thoughts.

      We are a “general purpose” organism — we adapt by being adaptable. Our great flexibility of body and mind, together with the power of accumulated culture, gives us our unique advantage in the biological world. Whereas most species have refined adaptations designed to exploit a specific environmental niche, we have been able to populate and dominate the entire globe.

      We can imagine a few ways we might like to improve ourselves, but it is not easy to see how altering our genes would accomplish these goals. Moreover, what we think we want today may not be what our children want tomorrow. This is the “flavor of the month” problem.

      And, on a more serious level, we may carry a kind of genetic “wisdom” that encodes millions of years of experience on the earth — a natural balance and breadth of adaptability to circumstances we cannot now remember or anticipate. We might end up altering something that is fundamental to our flexibility and range of freedom of response.

      It is a difficult thought for many people to even consider, and especially for evolutionary biologists, but it is just possible that we are already an optimized species (even with our evident weaknesses and frustrations).

      As the century unfolds and our gene editing powers are deployed on ever deeper levels, we may come to realize that any “improvements” for specialized functions have come with a loss of other more general advantages. We might just undercut the overall strengths of our species and head ourselves down the other side.

      It is worth pondering exactly why we think we need to be improved and yet, at the same time, have the confidence in our current capacities and clarity of mind to think we can chart our own course into a better human future. Perhaps one of the major outcomes of the era of gene editing will be a deeper appreciation of how wondrously we are made — of who we are (and, hopefully, not of who we were).

  9. Steffen Magnell says:

    If properly used, the Crispr technology will be of great benefit to humankind. Obviously, like any technology it can be abused and misused. Properly used it can be a boon to fighting genetic conditions heretofore untreatable and can help improve many other aspects of human genome development.

    • William B. Hurlbut William B. Hurlbut says:

      Yes, Steffen, I agree, the possibilities for doing good are fantastic. As you point out, the key is: “If properly used.” That is why serious discussion of the social and ethical implications of our new powers needs to begin — so we will proceed thoughtfully.

  10. If everyone is beautiful then no one is? Cookie cutter children (athletic, smart, artistic, etc.) sounds like a very dystopian future. CRISPR for disease repair? Yes. For picking physical traits? Not so good.

    • William B. Hurlbut William B. Hurlbut says:

      Mark, I agree, but the evidence drawn from our current culture suggests that people may want more than some standardized ideal. Human beings also greatly value individuality, social distinction, and even just public attention (sometimes even at the cost of their personal dignity, and even species identity). The varied styles of self-presentation, including major body alteration and mutilation, ought to give us pause.

      What strange and disturbing quests for uniqueness might be sought in a marketplace where gene editing technologies are available at the discretion of the client? Would the ‘cat-lady,’ or the ‘parrot-man’ want to have some genes from the species they most identify with? And, would they be allowed to intervene in the design of their children in alignment with their own images and desires?

      This is the other pole of the “cookie-cutter” scenario, and even if it is a hyperbolic concern, it needs to be put into the equation of discussion and policy formulation. It is not always easy to even define what we mean by disease or disability — there are reports of deaf couples intentionally selecting for genetic deafness in their children (though I’m not certain they are true). When “reproductive liberty” and fluid notions of personal identity are added into the equation, these discussions are likely to be difficult.

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