Revisiting the Ultranet's May, 2000, Interview with Dr. Michael West

 

 

Whatever Triggers Rejuvenation of New Life Must Reside in the Extra-Nuclear Body of an Egg Cell
    When Advanced Cell Technology (ACT) announced that it had cloned seven calves in April, 2000, it was pointed out that seven bovine ova were enucleated, and seven somatic cells aged in vitro almost to the Hayflick Limit were inserted in lieu of sperm. What seems notable about this is that whatever happened in response to the introduction of a cultured cell into the egg cell was not initiated or orchestrated by the nucleus of the egg cell, since it no longer had a nucleus. As Dr. West explained it,
    " ...we observed that an aged cell when introduced into an egg cell, results in the natural activation of telomerase to high levels, the extension of telomeres, and the extension of cell lifespan. "
    So what told the egg cell that it now had another cell inside it? What triggered the "natural activation of telomerase to high levels"? And what other clean-up mechanisms went into operation? Extending telomeres would, I should think, allow a cell to live and reproduce longer, but it wouldn't seem to refurbish either the genome or the rest of the cell to the level of perfection that would seem to be required for a "copy for posterity".
    Another interesting question is that of how a cell that isn't a sperm cell can impregnate an egg cell that lacks a nucleus and survive to produce healthy offspring. Nature goes to a certain amount of trouble to insure robust sperm cells. The testicles are mounted outside the body to keep them cool, a design that must expose them to elevated mechanical risk. In addition, they are tested for vigor, since only the fastest swimmer reaches the ovum. Perhaps the cell that Advanced Cell Technology employed was adequate under the artificial circumstances that ACT created, but wouldn't have passed muster in the wild.
    Whatever triggers cellular reconstitution must reside in the extranuclear body of an ovum.

Isn't Dolly, the Cloned Sheep, Aging Faster Than Normal?
Dr. West has this to say about Dolly...
    "Dolly was cloned from a cultured breast epithelial cell that in turn came from a 6 year old sheep.  As the readers may know, cells have a genetic “clock” at the end of each DNA strand called the telomere that can be “read” to tell the age of the cell.  So an interesting experiment is to measure the age of Dolly’s cells.  Wilmut showed in his 1999 paper reasonable data (though only one cell culture and one experiment) that telomeres were shortening as the breast cells aged in the dish, and that Dolly’s telomeres were shorter than age-matched non-cloned sheep.  Our approach differed in that we used cows rather than sheep, we use a different cloning technology (cells grown in the presence of adequate growth factors to promote cell division) and we grew our cells to old age before the transfer into an egg cell.  Beyond that explanation, I’m afraid I don’t want to elaborate at the moment.  We wish to protect certain patents. "

Will we be able to use this technology to lengthen our lifespans? How soon?
Dr. West's Answer:  "A simple answer of course, is that if we can cure a life-threatening disease, we extend the lifespan of that person.  But, of course, in that respect, we lengthen lifespans every day with penicillin.  What you are likely getting at, is there a way of extending the observation that we can reverse the aging of cells to whole organs or humans.  To some extent, we can see that this is possible.  In a thought experiment, we can imagine making body components one-by-one each made young by cloning.  Then our body would be made young again segmentally, like an antique car is restored by exchanging failing components.  But the fact that cell aging can be reversed in the dish may lead to a more profound molecular understanding of the mechanisms of aging that will allow more heroic interventions in aging.  We have some ideas in that regard.  By  the way, I once say a T-shirt that had a picture of Einstein, under the face it read, “If he was so God damned smart, why is he dead?”  The point is, aging is a disease that is killing everyone. "

Can the human body be genetically engineered in vivo to repair itself automatically, without need of technical intervention? If not, could a human clone be so-engineered in vitro? Can humanity be genetically reshaped into an ageless race?
Dr. West:  "We know, with a reasonable certainty that longevity is genetically determined.  Therefore, a reasonable person would conclude that humans could be genetically engineered to have extended lifespans, perhaps indefinite lifespans.  Engineering an existing human is even more challenging, however, but I’m optimistic about the prospects to dramatically improve how humans age, and for what I believe are good reasons.  Can the human body be engineered to repair itself?  I think so, yes, for the most part.  I can take a cell from a 100 year old person and make a brand-spanking new dimpled babe, doesn’t that in itself tell us something about the immortal substratum of life? "  

The prospect of a truly effective anti-aging therapy amplifies the danger of overpopulation. While statistics indicate that death by accident would be inevitable even in the absence of aging and disease, the maximum lifespan could grow to hundreds of years, thus allowing the birth rate to vastly exceed the death rate. Given the likelihood that the availability of anti-aging technology will spread despite the best efforts of governments to contain it, are politicians correct to be frightened of this prospect (that is, with regard to extending the lives of others as opposed to their own)?
Dr. West: "First, the work of a small (under funded) handful of scientists trying to tackle the dragon of human mortality should hardly cause any politician to lose any sleep.  I learned today (5/11/00) that India declared they have surpassed 1 billion people.  We have a world population problem anyway.  True, an elimination or slowing of human mortality would aggravate the problem, but we have to deal with it anyway.  And besides, why put the burden on people now living, people enjoying the process of breathing, people loving and being loved.  The answer is clearly to limit new entrants to the human race, not to promote the death of those enjoying to gift of life today. "


Has any attempt been made to modify naturally occurring DNA-repair enzymes to improve them? How many such repair molecules are known? 
Dr. West:  "I would argue that it is useful to think of life, such as human life, being an immortal lineage of cells that we call the germ line with somatic cells spinning off each generation.  Thinking of life that way, that is, seeing the chicken as an egg’s way of making another egg, one realizes that repair is likely highly evolved in the germ line.  After all these cells have no dead ancestors.  They are a continual lineage that have survived all insults thrown at them for billions of years.  So your question might be rephrased from “How could we improve the repair molecules” to “How can body (somatic) cells enjoy the repair of the germ line?”  One way is to look for differences in the germ line and soma.  That is how we tracked down telomerase, an immortalizing enzyme active in the germ line and generally not in the soma.  Nuclear transfer (cloning) is another approach, simply taking an aged somatic cell and returning it to the cytoplasm of the germ line.  Perhaps there are other strategies, CAN YOU THINK OF ANY?"