Wednesday, July 02, 2008

Metamorphosis   posted by Fly @ 7/02/2008 08:02:00 PM

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

Stem Cell Review Series: Regulating highly potent stem cells in aging: environmental influences on plasticity

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 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.

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