The third strand in the cord of cell biology is genetics and, like the other two, it has important roots in the 19th century. The strand begins with Gregor Mendel, whose studies with the pea plants he grew in a monastery garden must surely rank among the most famous experiments in all of biology. His findings were published in 1866, laying out the principles of segregation and independent assortment of the “hereditary factors” that we know today as genes. These were singularly important principles, destined to provide the foundation for what would eventually be known as Mendelian genetics. But Mendel was clearly a man ahead of his time — his work went almost unnoticed when it was first published and was not fully appreciated until its rediscovery nearly 35 years later.
As a prelude to that rediscovery, the role of the nucleus in the genetic continuity of cells came to be appreciated in the decade following Mendel&’s work. In 1880, Walther Flemming identified chromosomes, thread like bodies seen in dividing cells. He called the division process mitosis, from the Greek word for thread. The chromosome number soon came to be recognised as a distinctive characteristic of a species and was shown to remain constant from generation to generation. That the chromosomes themselves might be the actual bearers of genetic information was suggested by Wilhelm Roux as early as 1883 and was expressed more formally by August Weissman shortly thereafter.
With the roles of the nucleus and chromosomes established and appreciated, the stage was set for the rediscovery of Mendel&’s initial observations. This came in 1900, when his studies were cited almost simultaneously by three plant geneticists working independently — Carl Correns in Germany, Ernst von Tschermak in Austria and Hugo de Vries in Holland. Within three years, the chromosome theory of heredity was formulated by Walter Sutton, who was the first to link Flemming&’s chromosomal “threads” with Mendel&’s “hereditary factors”. Sutton&’s theory proposed that the hereditary factors responsible for Mendelian inheritance were located on the chromosomes within the nucleus.
This hypothesis received its strongest confirmation from the work of Thomas Hunt Morgan and his students at Columbia University during the first two decades of the 20th century. They chose Drosophila melanogaster, the common fruit fly, as their experimental species. By identifying a variety of morphological mutants of Drosophila, Morgan and his co-workers were able to link specific traits to specific chromosomes.
Meanwhile, the foundation for our understanding of the chemical basis of inheritance was also slowly being laid. An important milestone was the discovery of DNA by Johann Friedrich Miescher in 1869. Using such unlikely sources as salmon sperm and human pus from surgical bandages, Miescher isolated and described what he called “nuclein”. But, like Mendel, he was ahead of his time and about 75 years were to pass before the role of his nuclein as the genetic information of the cell came to be fully appreciated.
As early as 1914, DNA was implicated as an important component of chromosomes by Robert Feulgen&’s staining technique, a method that is still in use today. But little consideration was given to the possibility that DNA could be the bearer of genetic information. In fact, that was considered quite unlikely in the light of the apparently uninteresting structure of the monomer constituents of DNA (called nucleotides) that were known by 1930. Until the middle of the 20th, it was widely held that genes were made up of proteins, since these were the only nuclear components that seemed to account for the obvious diversity of genes.
A landmark experiment that clearly pointed to DNA as the genetic material was reported in 1944 by Oswald Avery, Colin MacLeod and Maclyn McCarty. Their work focused on the phenomenon of genetic transformation in bacteria and their evidence was compelling, but the scientific community remained largely unconvinced of the conclusion.
Just eight years later, however, a considerably more favourable reception was accorded the report of Alfred Hershey and Martha Chase that DNA, and not protein, entered a bacterial cell when it was infected by a bacterial virus.
Meanwhile, George Beadle and Edward Tatum, working in the 1940s with the bread mold Neurospora crassa, formulated the “one gene-one enzyme”’ concept, asserting that the function of a gene was to control the production of a single, specific protein. Shortly thereafter, in 1953, James Watson and Francis Crick proposed their now-famous double helix model for DNA structure, with features that immediately suggested how replication and genetic mutations could occur. Thereafter, the features of DNA function fell rapidly into place, establishing that DNA specifies the order of monomers (amino acids) and hence the properties of proteins and that several different kinds of RNA (ribonucleic acid) molecules serve as intermediates in protein synthesis.
The challenge of analysing the vast amount of data generated by DNA sequencing has led to a new discipline called bioinformatics, which merges computer science and biology as a means of making sense of sequence data. In the case of the human genome, this approach has led to the recognition that there are at least 35,000 protein-coding genes in the human genome, about half of which were not known to exist prior to genome sequencing. With the DNA sequences for these genes now known, scientists are beginning to look beyond the genome to study the proteome, which encompasses the structure and properties of every protein produced by a genome.