Metamorphosis
In discussions of nature vs. nurture a common assumption is that if it is in the genes then we can’t fix it. Or we can only change it by eugenics or bioengineering babies. I wish to suggest a different approach.
The following links provide background:
Bioengineered Stem Cells Rejuvenate Muscles In Mice
Stem Cell Review Series: Aging of the skeletal muscle stem cell niche
Autism-spectrum disorder reversed in mice
Essentially all tissues turn-over with time. Some tissues such as the gut lining are replaced every three days, other tissues such as bone and fat are replaced over decades. (Proven by tracking green florescent cell markers over time.) In the adult brain, neurons are seldom replaced but new neurons are continually produced and some repair occurs. I believe it will eventually be shown that all tissues contain stem cells that have the potential to rebuild that tissue. Pluripotent hematopoietic stem cells from bone marrow can, with the proper differentiation signals, produce every cell type in the body. Stem cells make up less than 1/10,000 of the cells in tissue. (Adipose tissue may have a higher frequency of stem cells. Satellite cells in muscle tissue may also be relatively common. I welcome correction if I’m wrong about other tissue types.) If scientists could replace that small stem cell fraction and increase the rate of cell turn-over then eventually most of the body cells would become the new type.
Each day a few hundred stem cells in the bone marrow mobilize, circulate in the blood, and either migrate to specific tissue sites, resettle into other bone marrow niches, or die. (This has been observed in mice by florescent labeling of transplanted stem cells.) By injecting a few thousand stem cells each day, a person’s original bone marrow stem cells could be gradually replaced. The process would be accelerated if stem cell mobilizing drugs were used. Or if the old stem cells were selectively targeted for destruction.
By itself, transplants using young stem cells don’t significantly repair damage or rejuvenate tissue. Proper signals are needed to mobilize the stem cells to the desired site, to cause the stem cells to divide, to cause the stem cells to differentiate into the right cells, and to cause those cells to integrate into the existing tissue. This is what happens when our body successfully heals a wound. For rejuvenation scientists also need to kill senescent cells and remodel the extracellular matrix. This isn’t easy but significant progress is being made.
Imagine that in ten years the technology existed to completely replace the stem cells in one mouse with stem cells from a different mouse. And that the tissue turn-over rate was increased so that most of the mouse body cells derived from the second mouse. How much remodeling of body and brain would occur? Some body structures would have been largely fixed during development but much would change due to the new cell DNA. Potentially, a sick or dull mouse could be made healthy or smart by such a full body stem cell makeover.
In addition there will be progress in restructuring damaged parts of the brain. This may require putting the tissues back in an earlier developmental state so as to rebuild a functional structure, e.g., regrow a nerve fiber connection. Memories stored in the original brain tissue structure would be lost but functionality would be regained after training. Even developmentally fixed traits might be altered by selective rebuilding of body structures.
The stem cell donors might be world class athletes, handsome, musically gifted, with IQ’s over 160. By expanding a cell line in culture, one donor could supply an unlimited number of recipients. Modest genetic engineering might improve the cell line. Even the germ cells would be replaced so future offspring would not be genetically related to the original person.
Would you choose to undergo such a metamorphosis? Externally you might change in just a couple of years. Your parents and friends might not recognize you. Internally you should have pretty much the same memories. However, your internal processing might be different and your personality might change. I think you would feel like the same person but you would also know that you were different. Like remembering how it felt to be depressed…you were you then and you are you now but you aren’t the same you. Hopefully your spouse would like the new you. This would be a little like massive cosmetic surgery.
This is a potential solution to the unfair distribution of good genetic traits. It could be a win-win for all groups. Defeat old age, class divisions, and racial strife in one stroke. I would do it to myself and would support having the government offer free treatment to everyone. It might even be offered as an alternative to execution or long term imprisonment.
Labels: life hacking, Stem cells
one thing i wonder, though, is if the genetically disadvantaged groups would be willing to take the “cures”? wouldn’t it become a point of group pride not to take the “other guy’s gene’s” pill? (LOL at neo-nazis taking shlomo’s allele). i guess its a question of individualism vs group pride. while there would be individualists, my guess is there would also be communes of the groupists, the naturalists whatever.. kind of like hippies but ethnocentric?
wouldn’t it become a point of group pride not to take the “other guy’s gene’s” pill?
this would be so fucking retarded i really can’t fathom it. that being said, frutitarians and christian scientists exist.
“wouldn’t it become a point of group pride not to take the “other guy’s gene’s” pill?”
I believe there are enough exceptional members in all large groups that a person could choose a donor from their own group. It would be up to the individual whether to change groups or not.
An exceptional individual with an IQ over 200 and demonstrated accomplishment might prefer to keep his own genes. Such an individual might convince others to use him as a donor. I imagine becoming a donor would confer high status.
I don’t really know how most people would react to this choice. For myself, it would be an easy. Grow old and deteriorate or renew myself in a better body. If the renewal process caused me to lose many important memories, the decision would be harder. I’d probably defer it until very old.
Also, I don’t really think of this as gene engineering, i.e., selecting and combining specific alleles. The stem cells would be from individuals known to have superior phenotype. Stem cell transplantation should be easier than genetic engineering of superior phenotypes. It would be more like cloning a superstar.
I believe there are enough exceptional members in all large groups that a person could choose a donor from their own group
Good point. But still, wouldn’t there still be some group stigma if the frequencies favored an out-group? Especially since the headlines that would come out (if not in the mainstream press then all over the web) with the genomic advances would be “Group X favored twice over group Y for controversial IQ genes discovery”.. taking it would be (wrongly or not) labeled by many group Y members as an admittance of intellectual inferiority[1] (many don’t want to contribute to the headline “Group Y seeks out controversial IQ gene in record numbers”). perhaps the cultural dynamics of “self-hating jew, uncle tom, white race-traitor” would take on a whole new power/meaning. i really wish that wouldn’t be the case but i can’t see how some of that wouldn’t be the case.
[1] the fact that it would occur in bell curves and in a complex statistical senses wouldn’t ease peoples nerves any more than that argument does right now without the final genomic word on it.
Wouldn’t implanted stem cells get rejected by the immune system?
Keith: “Wouldn’t implanted stem cells get rejected by the immune system?”
If you just injected adult stem cells from an immune incompatible donor without first destroying the the patient’s immune system then the transplanted cells would be rejected. As long as the donor cells are immune compatible then there is no rejection. There are multiple solutions to the rejection problem.
Choose a donor cell line that is immune compatible.
Do minor genetic engineering on the donor cell line so that it is compatible with all humans.
As part of the rejuvenation program, rebuild the immune system. This has the advantage that new immune system might attack the senescent cells of the old type. Immune suppressant drugs could be used to control the rate the old cells were attacked.
Advances in biotech to manipulate the immune system will have advanced to the stage where rejection can be controlled or stopped. I believe this level of immune system technology will be available before we have the technology for tissue rejuvenation. (Advanced immune system technology should also reduce the threat of cancer.)
Ben G.: “.. taking it would be (wrongly or not) labeled by many group Y members as an admittance of intellectual inferiority[1] (many don’t want to contribute to the headline “Group Y seeks out controversial IQ gene in record numbers”)
When the technology is commonly available I think such concerns would be marginalized.
The individual would mainly be focused on the difference it would make in their own life. Consider the popularity of cosmetic surgery and then imagine a treatment that made you younger, improved your looks, and made you smarter. Once people saw the results of the treatment on friends and family they would demand access for themselves.
The early adapters would be old, rich people. There would be strong public pressure to make the treatments available to everyone as a matter of social justice.
Those people that are committed to identity politics would want to make certain that “their people” didn’t get left behind. There might be racial pride initiatives to mobilize the group members to rapidly use the treatments.
I do see potential problems. The first treatments might go awry in numerous ways. People might demand access to the treatment before all the bugs are worked out. Also, what would the parent of an autistic child do?
Finally, I may be naive but I believe most people do want a better world for everyone. I suspect many liberals completely reject biological determinism because it provides no solution to social injustice. Likewise many conservatives reject “socially progressive” programs because they believe the programs don’t work and often make the problems worse. An effective technology would win converts from both groups.
There are more than frutiarians and kooky religious types.
Lesbian couple create deaf child like them.
http://jme.bmj.com/cgi/content/extract/28/5/283
Deaf demand right to design deaf babies.
http://www.timesonline.co.uk/tol/news/uk/health/article3087367.ece
Externally you might change in just a couple of years.
While I think this is a really promising line of therapy and look forward to seeing (and enjoying) the results, I think you’re glossing over the fact that a lot of higher-level structures are the result of a developmental process, and the results are not going to be changed by this maintenance or piecemeal replacement therapy. Things like the shape of your face, the length of your bones (for an adult), or the overall size of your brain are not going to be mutable via this approach. Other things like brain structure or the long-term statefulness of the immune system are not well enough understood for us to say what the limits of replacement metamorphosis would be.
Even the first signs of what we know we *can* change, though, are really promising. Just being able to undo the starvation adaptations that leave us all (effectively) lazy, depressed and weak would be an enormous boon.
bbartlog: “…you’re glossing over the fact that a lot of higher-level structures are the result of a developmental process, and the results are not going to be changed by this maintenance or piecemeal replacement therapy”
Yes, I’m glossing over a lot of stuff. There are significant questions regarding how plastic adult bodies really are. That is why I provided the link to “curing” the autistic mouse. There are traits that one would have thought were set during development that can be changed by rather crude genetic engineering on adult cells. I’d love to see mouse experiments that explored the plasticity of the adult animal, especially the adult brain.
I believe that large structural remodeling will soon be achieved. E.g., regrowing a finger or repairing a spinal cord injury. I believe present medical research will lead to rebuilding brain structures that have been destroyed due to injury or disease. It should be possible to enlarge the skull with surgery, allowing the brain to expand. I tend to believe that gradual changes in brain size and structure wouldn’t be too disruptive of existing memory and skills. Old people can recover from stroke and young children show significant plasticity in rewiring around damaged areas.
I don’t really know what to do about restoring nerve fibers that connect different brain regions. (Researchers are working on restoring the optic nerve connection. http://www.scienceblog.com/cms/node/7070 ) The original connections depended on a carefully orchestrated sequence of cellular events and signaling combined with external environmental feedback and pruning. Duplicating that process would likely destroy memories and skills. For the next few decades we might have to support the existing neurons with their axon connections by rejuvenating oligodendrocytes, astrocytes, and brain stem cells. That would limit potential intelligence improvements. (Brain rejuvenation is difficult.)
Statins have unexpected effect on pool of powerful brain cells:
http://www.eurekalert.org/pub_releases/2008-07/uorm-shu070208.php
“Scientists found that both compounds, when used at doses that mimic those that patients take, spur glial progenitor cells to develop into oligodendrocytes. For example, in one experiment, they found about five times as many oligodendrocytes in cultures of human progenitor cells exposed to pravastatin compared to cultures not exposed to the substance. Similarly, they found that the number of progenitor cells was just about one-sixth the level in cultures exposed to simvastatin compared to cultures not exposed to the compound.”
“These are the cells ready to respond if you have a region of the brain that is damaged due to trauma, or lack of blood flow like a mini-stroke,” said Sim, assistant professor of Neurology. “Researchers need to look very carefully at what happens if these cells have been depleted prematurely.”
“Glial progenitor cells are distributed throughout the brain and, according to Sim, make up about 3 percent of our brain cells. While true stem cells that can become any type of cell are very rare in the brain, their progeny, progenitor cells, are much more plentiful. They are slightly more specialized than stem cells but can still develop into different cell types.”
Very interesting. That probably explains this. Relevant passage: ‘Put another way, someone who uses statins currently is 92% as likely to develop Alzheimer’s as someone who never used statins, yet someone who previously used statins and stopped statin therapy is 254% as likely to develop Alzheimer’s disease than someone who never used statins.
fly –
i worry about the neocortex. during development an initial set of stemcells differentiates into radial glia and neural progenitors. the neural progenitor gets its ‘cellular identity’ and position in the circuit by being born after a certain number of cell divisions and at a certain spot on the ventricular zone. the newborn neurons climb up radial glia to their spot close to the developing skull surface.
one concern is that radial glia may not know how to be big enough to reach from the ventricular zone to the skull of an adult.
another concern is the surgical precision it would take to stick a dot of neural stem cells in the right spot.
point is there isn’t anything like a niche anywhere terribly accessible to where adult neocortical neurons are hanging out.
but i’m down for all the stuff besides brain mods. since i don’t know how complicated those places are i assume it’ll work. :)
re: Neural development of the cortex.
Kaleidoscopik, clearly your concerns are justified. My reply is more of an intuition and a hope than a prediction.
The brain may have repair mechanisms separate from the developmental program. I.e., when a neuron dies then brain stem cells and progenitor cells migrate to the wound site and differentiate into the proper neural type based on the chemical, mechanical, and electrical signals in the local environment. Perhaps many new neurons would be produced and only those that made proper connections would survive. (I suspect that is how the new neurons generated in the dentate gyrus of the hippocampus help in the formation of new memories.) The mouse brain continually replaces neurons lost in the olfactory bulb (where they are exposed to a harsh environment). The new cells must migrate significant distances and properly integrate into functional tissue. So at least some parts of the mouse brain already self-repair. I also believe there is evidence for minor levels of repair in other brain tissues. If so, it might be relatively simple to renew brain tissues by temporarily increasing the neuron production rate and decreasing the new neuron apoptosis rate while targeting senscent cells for destruction.
I suspect that mammals brains are more plastic than insect brains. I.e., brain circuitry in drosophila is genetically controlled down to the low level structures while only the upper level architecture is fixed in mice. If so, then the repair would just have to be in the right ball park and then training would optimize the resulting tissue. If this is the case then we might not need to replicate the developmental path that creates cortical minicolumns. Instead, cells would migrate to a region that was sending signals indicating repair is needed. There they would divide and differentiate into the appropriate neurons. The local tissue environment would provide the signaling needed to organize the cells into a functioning cortical minicolumn.
“another concern is the surgical precision it would take to stick a dot of neural stem cells in the right spot”
Yes, my hope is that other cell migration methods already exist in the brain and that we only need to supply stem cells to the cerebrospinal fluid and increase the rate of cell turnover. If instead we have to directly insert the right cells in the right location and directly controlled the local signaling environment then rejuvenation becomes much harder. In that case we would need robotic micro devices to do the implanting. That would take several more decades of technological advance.
Bbartlog, good connection to that earlier paper. Thanks for the link.
The trouble is that the result of such a makeover would no longer be me. My memories, yes, but not my genome. Identity is in my view a function of both.
I would consent to replacement of particular defective genes but not to replacement of my whole genome.