A Guide to Cancer

Origins and Revelations

Melford John

• Publisher: CRC Press
• Year: 2017
• ISBN:
  9781351721806
• Edition: 1
• Topic: Médecine
• Subtopic: Théorie, pratique et référence de la médecine

A Guide to Cancer: Origins and Revelations unfolds the complex and fascinating topic of cancer in two ways: firstly, no specialist knowledge is assumed on the part of the reader, and secondly, despite the serious nature of the topics, the book aims to stimulate interest, provoke thought, and paradoxically entertain. It takes an array of complex topics and breaks them down in clear, concise terms, so that anyone with a basic knowledge of science can understand. The book is aimed at the general public as well as students of biological subjects, first and second year university students, and researchers in the nascent field of cancer genomics.

1

Origins

Cancer is driven by genetic aberrations that occur spontaneously on a daily basis. It is more complex than any other disease and is our greatest medical challenge. In recent times, cancer has emerged as one of the leading causes of death in developed countries. According to figures from the American Cancer Society, 1630 Americans would have died each day from cancer in 2016, amounting to 595,690 for the whole year. Cancer is the second most common cause of death in the United States, exceeded only by heart disease, and accounts for nearly one in every four deaths. During the average person’s lifetime in the United States, there is a 42% chance of becoming a victim of cancer. As genetic aberrations accumulate with time, the risk of developing a tumor increases with age. Approximately 70% of estimated deaths for the four major cancers (lung and bronchus, colon and rectum, breast, and prostate) occur past the age of 65. What do we know of cancer? Why is it so difficult to cure? How can we reduce the risk of it developing?

We begin by examining the origin of cancer, what causes it. To do so, we need to become familiar with some basic biological terms related to the fascinating topic of molecular genetics. Let us take a trip back in time starting with the pivotal contributions of a Greek philosopher, an Italian poet, an English naturalist, and an Austrian monk. This could be the beginning of a funny joke, “they all walked into a bar,” but it’s not. Stay with me, lend me your ears. Let us boldly distill the essence of their works, and marvel at the creativity and elegance of it all.

1.1 Charles Darwin

In 1859, Charles Darwin, an English naturalist, published On the Origin of Species by Means of Natural Selection, in which he proposed a theory of evolution that occurs by a process of natural selection. In a changing world, life forms compete for limited resources such as food, water, and shelter from predators. Darwin worked on his theory for 20 years and concluded, animals and plants that are better able to compete are more likely to survive and reproduce. Over a period of time, species that adapt to their changing environment survive, while those that fail become extinct. In short, survival of the fittest. Figure 1.1 shows photos of Charles Darwin and Gregor Mendel.

Figure 1.1 Charles Darwin and Gregor Mendel.

It’s obvious once said, but to step back and observe nature’s thriving, resplendent creatures, to take note of subtle differences, and from that, shape a paradigm that fundamentally conflicted with established beliefs of the day took a creative, unhindered mind. Although he didn’t know it at the time, Darwin was not the first to suggest that man was descended from animals, nor was he the first to introduce survival of the fittest as a concept.

1.2 Anaximander

More than 2500 years ago, the ancient Greek philosopher Anaximander (610–546 BC), credited by scholars as one of the greatest minds that ever lived, presented an explanation of the origin of man based on observations of nature. He suggested life originated from moisture that covered the earth before the sun evaporated it, and the first animals were a kind of fish, with a thorny skin. He also proposed that humans were not present at the earliest stages of the earth, but arose from fish later.

Even though his ideas were influenced by religious and mythical abstractions particular to his time, Anaximander was one of the first to attempt to explain the origin and evolution of the cosmos based on natural laws. He proposed the abstraction of “the boundless” as the origin of all things, and is credited as the originator of the theory of an open universe, which eventually replaced the notion of the closed universe of the celestial vault. To illustrate how ahead of his time Anaximander was, by comparison the ancient Greek philosopher Empedocles (490–430 bc) suggested the world was made up of the four elements: fire, water, earth, and air more than 50 years later.

1.3 Titus Lucretius Carus

The writings of the ancient Roman poet and philosopher Titus Lucretius Carus (99–55 bc) made more than a passing reference to survival of the fittest over 2000 years ago. Lucretius’ poem, the title of which translates to On the Nature of Things or On the Coming into Being of Things, consists of 7400 lines that extoll his philosophy on a wide range of topics including pleasure, religion, death, the physical world, and the nature of diseases.

He proposed a theory of evolution in which plants and animals were born out of the earth by the random combination of elements, after which the formation of new species ended. Natural selection led to “the ages after monsters died.” Those organisms that “preserved alive” did so because of their greater fitness to survive, exemplified by their “cunning, valor, speed of foot or wing,” and because of their usefulness to man. Lucretius did not believe in the descent of a new species from previously existing ones as Darwin did, and denied that land-dwelling animals evolved from marine animals as Anaximander proposed.

… And in the ages after monsters died,

Perforce there perished many a stock, unable

By propagation to forge a progeny.

For whatsoever creatures thou beholdest

Breathing the breath of life, the same have been

Even from their earliest age preserved alive

By cunning, or by valor, or at least

By speed of foot or wing. And many a stock

Remaineth yet, because of use to man . . .

On the Nature of Things by Lucretius

Translated by William Ellery Leonard

Lucretius considered people to be made up of the same matter as everything that surrounded them, such as the stars and seas. He proposed that we should follow the pursuit of pleasure and avoidance of pain, as an alternative to living in fear of the gods. Though the gods exist, he suggested they neither made nor manipulated the world, and lived unconcerned with human affairs. Lucretius believed human beings should conquer their fears, come to terms with the fact that all things are transitory, and embrace beauty and the pleasures the world offers.

1.4 Gregor Mendel

Around the same time that Darwin was pondering the infinite, Gregor Mendel conducted meticulous crossbreeding experiments with plants, on which many of the rules of genes and their inheritance were established, now referred to as Mendelian genetics. Although not known at the time, Mendel’s rules though developed from work on plants, apply to all living things that reproduce via sexual means. Mendel discovered that when purebred white-flower pea plants were crossbred with purebred purple-flower pea plants, the result was not a mixture of white and purple flower pea plants; all offspring were purple-flower pea plants. This led to the conclusion that there had to be two different traits for the color of the flowers, only one of which was expressed. All the first-generation pea plants were purple because the trait for this color was dominant, while the trait for white was recessive. Mendel also found that although not present in the first generation of plants, white flowers appeared in later generations.

Mendel’s work led to the following conclusions:

•The inheritance of a trait is determined by units or factors that are passed on from parents to offspring unchanged.

•An offspring inherits a single trait from each parent.

•A trait may not show up in an offspring, but may still be passed on to future generations.

Today we can explain Darwinian evolution using Mendelian genetics.

1.5 About genes

The Danish botanist Wilhelm Johannsen coined the term gene used to describe Mendelian units of heredity in 1909, some 50 years after Darwin’s publication on natural selection. He also made the distinction between the outward appearance of an organism, its phenotype, and its genetic traits, its genotype. Thus, the color of a flower is its phenotype, while the gene that codes for it is its genotype.

Genes are linear sequences of the molecules, guanine, cytosine, thymine, and adenosine that are chemically bonded together. They are commonly abbreviated to G, C, T, and A, respectively. Collectively they are referred to as bases. The bases are members of a type of chemical known as deoxyribose nucleic acid (DNA). It is commonly used to refer to genetic material representing any number of bases or genes. Who would have thought that the magic building blocks of the code for life would be four simple molecules? Another, perhaps more primitive genetic material, is ribose nucleic acid (RNA). This is similar in structure to DNA in that it is made up of four bases, but the bases are slightly different.

Genes vary greatly in length, from around 500 bases for the smallest human gene to over 2.2 million bases for the largest. Due to their vital importance for survival of the species, they are stored in a separate compartment in cells, away from potentially harmful chemicals in a structure known as the nucleus. Every cell in our body has a nucleus that contains a copy of the full complement of our DNA. Every cell that is, except for red blood cells and cornified cells in the skin, hair, and nails. Human red blood cells get rid of their nuclei on maturation to reduce their size for ease of circulation, and to increase their capacity to carry oxygen.

1.6 Decoding life

The full complement of genes in any living creature is referred to as its genome. In other words, the template used to create it. The sequencing of the genomes of many forms of life is currently taking place. The first animal genome to be sequenced was the nematode worm in 1998, which is composed of 100 million bases coding for 19,000 genes. In a mere 3 years, the human genome was found to consist of 3.2 billion bases. The first draft of the sequence was published in 2001. It was originally estimated that the human genome would consist of 100,000 genes, but that figure has been revised downwards on a number of occasions to the point where it now stands at 19,000. Surprisingly, we have around the same number of genes as the humble nematode worm.

From observations of peas, to genes, to decoding life itself, the word “awesome” was created for just these circumstances. In the words of the song “Rally Round the West Indies,” by David Rudder, “little keys can open up mighty doors.” Mendel, one imagines, might be moved to sing along with, “little peas can open up mighty doors,” with perhaps a celebratory tipple of wine. Or maybe he would have no time for such frivolity, what with peas to cross-pollinate, prayers, and the like.

The templates of life for the 8.7 million different life forms that exist on our planet are all made up of DNA. Some viruses use RNA, but I’m controversially excluding them from the club of life as they are unable to replicate on their own. If there was a constitution for life forms, this would be a blatant violation of the first paragraph of the first article: “no self-respecting life form shall employ th...