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The Cellular Basis of the Immortality of Species

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The phrase “immortality of species” refers to the fact that while the individual organism ages and dies, the species itself has the potential to regenerate new individuals indefinitely. Put simply, while any one zebra in Africa may die, there are always more, and they always look more or less the same. Years ago, my mentor Dr. Samuel Goldstein handed me the picture shown below of a young girl, her mother, her mother’s mother, and her mother’s mother’s mother.


At the time, it crossed my mind that a similar snapshot of the thousands of generations preceding these women would still be insufficient to fully appreciate the human life cycle’s profound dichotomy between mortality and immortality, which was described by 19th-century physiologist and comparative anatomist Johannes Müller as follows:

"Organic bodies are perishable; while life maintains the appearance of immortality in the constant succession of similar individuals, the individuals themselves pass away."

The quest for immortality itself appears to stretch back for an eternity. Most religious traditions have a concept that accounts for the immortality of an intangible part of each individual. The ca. 4000-year-old Epic of Gilgamesh is one of the earliest works of literature inquiring into the immortal renewal of life, in the story of Sha naqba ?muru, or "He who Saw the Deep". The ancients saw the mission to fight disease and death as a complex labyrinth, a puzzle that could only be solved by tracing back along the length of the thread that weaves countless lives together across the millennia.

To better understand the conundrum of the immortality of species, let’s also peer “into the Deep” by starting with the same question the ancient philosophers formulated:

“What allows a species to continue in an immortal fashion, across the millennia, while each individual is destined to age and die within a relatively short time?”

We could refine the question with the help of 19th-century scientific investigators, who considered the possibility of some kind of mechanism—a molecular key of sorts—specific to reproductive cells that could rewind the clock of aging. At the time, scientists sitting in front of their microscopes were just beginning to describe how life arises, in each generation, from reproductive cells. The field they invented we now call embryology. Such early studies into the cellular basis of life led the German naturalist August Weismann to speculate that the substance of heredity is transmitted via an immortal lineage of cells he designated as the germ-line.

First, Weismann postulated that the evolution of life as we know it probably involved a process beginning with single-celled organisms much like those we still see swimming around in pond water. Borrowing a spiritual term for this scientific purpose, Weismann posited that these organisms were, in a sense, immortal, by which he meant that they didn’t necessarily die, but rather they had the option of dividing into two daughter cells, one or both of which also had the potential to escape death by continuing to proliferate in this manner, day after day, year after year, and, eventually, millennium after millennium.

At some point in the history of life on earth, some of these immortal, single-celled organisms presumably clumped together to form a multicellular organism, known as Pandorina morum (see I, below). Pandorina morum may have had an advantage in that it could move faster than its single-celled cousins toward light or food. Then, many millennia later, P. morum may have evolved into another primitive organism similar to Volvox minor (see II, below). Weismann emphasized that the subtle evolutionary shift that would have occurred in these organisms was of great significance to biology.

I. Pandorina morum is an organism in which all the cells have the potential to regenerate another similar animal in an immortal fashion.
II. Volvox minor is an animal where the is a lineage of specialized somatic cells destined to die in that generation. Reproduced with modifications from Weismann, 1904.

In P. morum, all of the cells are potentially immortal, capable of making another P. morum. However, in the case of V. minor, only a small subset of cells retained this immortal characteristic (labeled “kz”, now called germ-line cells). Unlike the smaller, immortalized subset of cells, most cells specialized into body
(somatic) cells (“sz” in Weismann’s drawing). Somatic cells served to protect the internal germ-line cells. As a consequence of changing into a different type of cell via a process called differentiation, the somatic cells had lost their power to continually regenerate the organism.

Thus, Weismann came to the very simple conclusion that heredity is likely passed along through these germ-line cells and that their capacity for immortal proliferation is the basis for the immortal transmission of heredity.

Today, this may seem all too obvious. However, in Weismann’s day, this line of reasoning wasn’t obvious to anybody, and it directly opposed the prestigious theory of heredity proposed by Charles Darwin himself (Weismann, 1891). For our purposes, I have summarized Weismann’s view of life in the diagram below. The immortal germ-line cells are shown in green (sperm and egg distinctions omitted), and the cells that branch out to make the individual human being, the somatic cells (soma), are shown in black. Today, there are still at least two corollaries to Weismann’s model of the germ-line/soma dichotomy. The first concerns chickens and the meaning of life, and the second the “strategy” of death carried out by the soma.

As for those chickens: from your perspective, which of the following is true?

A.) An egg is a chicken's way of making another chicken.
B.) A chicken is an egg's way of making another egg.

Most of us would choose A. But Weismann’s theory suggested that in reality, the soma (or in this case, the chicken) evolved as a means to replicate the germ-line. According to this model, the chicken is a disposable transport vehicle, an appendage that evolved later, as sort of an afterthought. It is admittedly disheartening to consider that the chicken—who undergoes the wonderful metamorphosis from a single cell to an animal that breathes, possesses a beating heart and a brain, and can learn, rear its offspring, and spend its days in the summer sun—would take marching orders from the egg, an innocuous looking thing that just sits there for a short period of time until it becomes another chicken, or someone's breakfast.

The most dizzying aspect of this sudden inversion on the tightwire of life comes into view when we consider the implications for human life. Some feel that human dignity is undercut by the suggestion that human life evolved as a sophisticated reproduction machine for the immortal human germ-line cells. (We can imagine a similar disruption of the established hierarchy upon suggestions that our earth and sun were not, after all, at the center of the universe.) This existentially vertiginous perspective on our personal biographies is propagated by contemporary scientists like Richard Dawkins, author of “The Selfish Gene”. Like Darwin’s theory of evolution, such dethroning of the individual human being strikes to the heart of the human condition, tempting us to wonder things like the following:

“What, then, is the meaning of our lives, if sperm and egg cells really are the masterminds? Does this mean that we are of less value?

(In spite of the vertigo—or perhaps even because of it—some scientific adventurers experienced an exciting new perspective for ancient human values, and perhaps even the foundations of new ones. I will discuss some of these issues on the page titled “Philosophical and Ethical Considerations.”)

The second corollary of Weismann’s germ-line/soma dichotomy revolved around the fact that some cells were “programmed” to die. Following the rearing of reproductively competent progeny, the continued viability of somatic cell lineages had little selective value to the germ-line. Indeed, the continuity of surplus somatic cells may necessitate that surviving cells compete for scarce nutritional resources. So, in the end, the somatic cells were expendable, and indeed, their death could in some cases improve the prospects of the germ-line cells for overall success in the competition for survival. In other words, while all cells were at risk of death, for the somatic cells, death was—for the first time in evolutionary history—part of the “strategy”. (For those of you with a background in evolutionary science, please understand that these generalizations about the selection of mortality in the soma are meant only to communicate the concept that there ceased to be a selective pressure for the survival of somatic cells at some point in evolutionary history.)

So, according to Weismann, the lifespan of the soma was timed for optimization of the reproductive cycle, and for no longer than that:

"We should therefore expect to find that, as a rule, life does not greatly outlast the period of reproduction except in those species which tend their young; and as a matter of fact we find that this is the case." (Weismann, 1891).

In other words, Weismann suggested that one day it would be determined that in the case of humans, somatic cells would be shown to have a finite capacity to divide, whereas the germ-line cells would have an indefinite capacity for division. Both of these predictions were later to be proven true. Indeed, a cornerstone of modern gerontological research is based on the observation of Leonard Hayflick that cells from the human body show a finite lifespan when cultured in vitro (Hayflick 1965, 1968, 1992; Hayflick and Moorehead, 1961; see “Aging Under Glass”, on this website). In addition, when human embryonic stem cells were first isolated, they were shown to be the first normal immortal human cells ever cultured in the laboratory (which led me to call my account of their isolation “The Immortal Cell”. More on human embryonic stem cells can be found on this site under “Human Embryonic Stem Cells”).

Unfortunately, in his own day, Weismann didn’t have the tools to decipher the clockwork mechanisms of mortality and immortality, and he concluded that mankind had:

"We have hirtherto been without a scientific conception of immortality: we must understand by this term - not life without beginning or end - but life which, when it has once originated, continues without limit, accompanied or unaccompanied by modification (viz. specific changes in unicellular organisms, or in the germ-plasm of multicellular forms”

Today we are privileged to be living at a time when, for the first time, powerful new tools for uncovering the minute molecular mechanisms of life have revealed these mechanisms of immortality. In his lecture “Science and Immortality”, the celebrated physician William Osler eloquently described the wonder of germ-cell biology, a description that with minor modifications would hold up to scientific scrutiny even today:

“This marvelous embryonic substance is eternally young, eternally productive, eternally forming new individuals to grow up and to perish, while it remains in the progeny always youthful, always increasing, always the same. 'Thousands upon thousands of generations which have arisen in the course of ages were its products, but it lives on in the youngest generations with the power of giving origin to coming millions. The individual organism is transient, but its embryonic substance, which produces the mortal tissues, preserves itself imperishable, everlasting, and constant.”

References

Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614-636.

Hayflick L (1968) Human cells and aging. Sci Am 218:32-37.

Hayflick L (1992) Aging, longevity, and immortality in vitro. Exp Gerontol 27:363-368.

Hayflick L, and Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585-621.

Weismann, A. (1891) Essays upon Heredity and Kindred Biological Problems Vol I, Clarendon Press, London.

Weismann, A. (1904) The Evolution Theory, Edward Arnold, London. p257.

West, M.D. 2003. The Immortal Cell. Doubleday (ISBN 0-385-80928-6).

 

© Copyright 2012 Michael D. West, All Rights Reserved


 
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