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Cellular Self-Sacrifice — And an Allegory

Ann Gauger

apoptosis

We naturally think of death as something awful, a scourge to be dreaded and put off for as long as possible. But biological death has its positive side. Think of self-sacrifice — death for the good of others. That kind of death we think of as altruistic, even noble, attributing it to heroes or saints. And most of us don’t realize that such self-sacrifice is written into our bodies, at the deepest levels of our being.

The process is called apoptosis, in which cells kill themselves from within. It is not death due to overwhelming damage — that’s another process and called by another name. Rather it is a programmed process whereby cells self-destruct. They shred their DNA, internal organelles (specialized parts of cells) condense, and membranes bleb (blister). Then scavenger cells come by and clean up the remnants for recycling.

Programmed Cell Death Is Necessary

Cells are following their own programming when they kill themselves, but it can’t be accidental that such a program exists. Special biochemical pathways have been designed to carry out this self-destruction — quite complex pathways. Multiple signals feed in, turning genes on or off, so it doesn’t all happen in the wrong place or at the wrong time. It’s essential that the whole finely tuned system works in proper sequence.

So why does such a process exist? It doesn’t make sense that biology, which is mainly about survival and reproduction, should have a programmed process for cellular suicide. Yet apoptosis is necessary for our survival, and we are only beginning to understand why.

For example, cellular death shapes our bodies at the beginning of our lives, when we are formed in our mothers’ wombs. A human embryo at five to six weeks after fertilization has stubby limbs with paddle-like hands and feet. By the eighth week, the hands and feet have distinct, separate fingers and toes, because the cells in the webbing between the fingers and toes have undergone apoptosis.

Beginning in the third week after fertilization, cell death shapes our nervous system. Certain cells in the developing embryo undergo apoptosis. Their death causes other cells to move into the places they left behind and to multiply in response. All this movement and growth causes the sheet of cells to which they belong to change shape and round up into a hollow tube that will become our brain and spinal cord. That tube then sculpts itself by a combination of growth, migration, and apoptosis into distinct regions of the brain. Later, apoptosis is involved in another complex series of foldings that produce the structures that will become our eyes and ears.

We are born with more neurons than we can use, and the connections between neurons are unorganized. As we grow and learn, neurons form new connections. Repeated stimulation of neurons causes them to increase the number of their connections. Neurons that aren’t stimulated or don’t find the right partners die by apoptosis. Patterns begin to emerge in the connections, producing an efficient neural network that allows the growing child to learn to walk, throw a ball, or talk.

Regulates Immune System

Our immune system is kept in balance by apoptosis. Cells that defend us against disease have to learn to distinguish foreign cells and viruses from our own tissues. We carry within us an army with enormous destructive potential. This army is supposed to be trained to distinguish friend from foe, so that friendly-fire incidents, or wholescale assaults don’t occur. The army is our immune system. As new immune cells are produced, they have to pass through the thymus to teach them the difference between self and not-self. Any cells that react against our own tissues are triggered to die by apoptosis, so they will not attack our bodies. This is essential. If immune cells become resistant to the signals that trigger apoptosis, they can become marauders in our own bodies, attacking joints (arthritis), the thyroid gland (Hashimoto’s disease), the pancreas (diabetes), or worse, many tissues at once (lupus). Apoptosis also prunes away immune cells that are no longer needed after an infection is over. It’s apoptosis that keeps the immune system tuned for defense, but only when needed.

When cells are damaged by radiation, chemicals, or viral infection, the damage triggers programmed cell death in the now unhealthy cells. Apoptosis helps to protect us from illness and aging. But if mutations occur that block apoptosis, cells become “immune” to death. They can go on to multiply uncontrollably, becoming what we call cancer. Cancer is the ultimate selfish disease, where cells take resources and grow uncontrollably, poisoning everything else with their waste products. Because they lack the fail-safe pathway called apoptosis, they may also be resistant to things like chemotherapy or radiation. Damage no longer triggers programmed cell death.

An Allegory

No one knows how apoptosis came to be, although there are theories. Even the simplest of animals are programmed for apoptosis, so it has been around since the dawn of multicellular life. Perhaps it’s because cells need to live together in one body, so they must have a way of maintaining balance. No uncontrolled growth can be tolerated, or the whole organism ceases to be.

So what is the purpose of programmed cell death? Science alone cannot answer that question, because saying that cellular behavior has a purpose implies intentionality. Cells do it without souls or conscious thought; they simply do what they were made to do. We have to resort to the language of purpose and intention to explain programmed cell death. Cells do it to shape tissues. They do it to prevent harm to their neighbors. They do it when their presence is no longer needed, to clear the way for what is to come. They do it to maintain a balance between cells being born and cells dying. They do it so that multicellular creatures can exist.

They do it so that we might live — an allegory hidden in our very flesh that we have only now come to know.

Image: A astrocyte (kind of neuron) stained for particular proteins. The purple blue ovals are the nuclei where the DNA is; by GerryShaw [CC BY-SA 3.0], via Wikimedia Commons.

Cross-posted with permission from Dr. Gauger’s website, Making Notes of the Moment.