How the puzzle of the hereditary trail was finally explained

 

People have wondered since ancient times how the characteristics of parents are passed on to children. The puzzle was finally solved in the 1950s in probably the greatest scientific advance of the 20th century. This breakthrough gave birth to genetic engineering, molecular genetics and modern biotechnology. These developments touch all our lives, and we are only at the beginning.

Mere mention of the terms DNA and the genetic code conjures up images of Francis Crick and James Watson, who solved the structure of DNA in 1953. But, as is the nature of science, their breakthrough was only possible because of previous discoveries made by many other scientists.

In the fourth century BC Aristotle proposed that semen contained plans that directed the unformed maternal blood to shape offspring. In the Middle Ages, Thomas Aquinas "explained" that vigorous seed developed into males and weak seed produced females.

Later, sperm cells were examined in the light microscope. It was "observed" that each contained a tiny pre-formed child, termed the homunculus. The mother was thought to merely incubate the homunculus, who emerged as a baby nine months later.

Modern genetics began with Gregor Mendel's brilliant experiments on heritability in pea plants. Mendel showed that discrete hereditary elements (genes) are responsible for hereditary traits. These genes are passed on by both parents and the genes can independently sort and segregate between offspring.

The scientific world was not ready for Mendel's results, published in 1865. His concept of the sorting and segregation of discrete hereditary units could not be fitted into the crude understanding of the cell then available. He also used a statistical approach, which was foreign to current biological thinking.

Mendel's work was rediscovered at the turn of the century, by which time the rest of science had caught up. Chromosomes (the structures in the cell nucleus bearing the hereditary material) had been discovered, and the processes of cell division and the sharing of genetic material, mitosis and meiosis were understood. Mendel's theory could now be painted on to structures visible in the microscope. Also, the use of statistics was by then common in biology.

An explosion of developments in genetics now began. It became clear that genes were arranged linearly along chromosomes and that they could undergo sudden permanent changes, mutation, resulting in changed traits in the organism. Genetics could also explain the mechanism of evolution. Mutations are the main source of novelty in evolution and natural selection chooses organisms bearing novel genes that make them better suited to survive in the environment.

Genetic understanding made it possible to design breeding programmes to improve animal and plant varieties and in medicine it opened the way to design interventions for prevention and cure of disease.

Yet the molecular mechanism whereby the gene exerts its effect remained a mystery, although interesting speculation was in the air. In 1945 Erwin Schrodinger published a book What is Life. He suggested that the gene was a one-dimensional aperiodic crystal of a few repeating elements whose pattern of succession represents the hereditary information.

In 1944 O.T. Avery and co-workers showed that genes must be embodied in Deoxyribonucleic Acid (DNA), known since 1920 to be a major component of chromosomes. However, structurally it was thought that DNA was made of identical repeat units and therefore incapable of bearing information.

In 1952 A.D. Herschey and M. Chase again demonstrated that genes were made of DNA. By now much more was known about the structure of DNA. In 1950 Edwin Chargaff had shown that DNA from different biological sources showed distinct differences and could carry information.

Four kinds of chemical structures are linked together in DNA: Deoxyribose, Phosphoric Acid, Purine Bases (Adenine, A), (Guanine, G), and Pyrimidine Bases, (Thymine, T), (Cytosine, C). Chargaff showed that DNA from different sources had different relative amounts of A, T, G and C, and that, regardless of source, A and T were always present in equal proportions, and G and C were always present in equal proportions.

In the late 1940s/early 1950s, W.T. Astbury, Maurice Wilkins and Rosalind Franklin produced vital X-ray diffraction pictures of DNA showing it was probably a two-stranded helical structure. Francis Crick and James Watson, using X-ray diffraction and model-building, and drawing on all the available evidence, solved the structure of DNA in 1953.

The DNA molecule is a double helix in which two strands wind around each other. Deoxyribosephosphate makes up the backbone of each stand, and the bases protrude from these backbones into the heart of the double helix. A always links to T on the other strand, G always links to C. Information in DNA resides in the base sequences. One unit of information is represented by a sequence of three bases. The four letters of the genetic alphabet (A,T,G,C) can therefore form 64 units of information (4x4x4).

The structure of the genetic material is, like all great truths, elegantly simple, and simply beautiful. Watson and Crick made their breakthrough as young men. They have since been feted as heroes. And indeed they are great scientists. But they enjoy their fame because science was ready to hear what they had to say. Their results were not premature, like those of poor Gregor Mendel, who died a lonely death with his great work unappreciated.

William Reville is a senior lecturer in biochemistry at UCC