Imprimir Republish

Human Genome

Genetics and Genomics: 135 years of scientific research

What the future holds is broad horizons and dead-end alleys

Everything began in the late 19th century, with an Austrian monk who was greatly interested in natural history, and the peas that he grew in his monastery garden. From this sprang the so-called “Mendel laws”, which provided the basis for the whole structure of genetics and molecular biology. Unfortunately, these principles were ignored until 1900, when their significance was finally understood. Over the next 35 years, a solid body of doctrine was established shedding light on the mysteries of biological inheritance.

Regardless of what happened in genetic laboratories, a London doctor, Frederick Griffith, observed a curious phenomenon in 1927; the transformation of pneumococci, which had a particular protection capsule against the immunological system of its host (in this case, mice), into another. Again, the importance of the discovery went unnoticed (including by Griffith himself), and it was only 17 years later that Oswald T. Avery and his associates verified in the United States that the “transforming agent” was a substance called deoxyribonucleic acid, whose symbol, DNA, is now on everyone’s lips.

We should not conclude, however, that the acceptance that DNA was the genetic material was peaceful. There was a good deal of discussion (the alternative was that it would be a protein). One of the important experiments leading to general acceptance was undertaken in 1952 by the Americans Alfred Hershey and Martha Chase, who used a simple blender to do it!

And then, the year after, the seminal work of James D. Watson and Francis M. Crick on the double helix structure of DNA was published, followed in 1961, by the explanation of the genetic code. The rest is recent history. More details are given in the table.

At this point, a brief reflection on the advance of science is appropriate. Thomas S. Kuhn, established convincingly in 1962 that scientific development progressed by revolutions causing earlier paradigms to be demolished, followed by periods of “normal science”.  The immediate failure to recognize fundamental discoveries such as those of G. Mendel and F. Griffith is explained by a phrase attributed to the physicist Max Planck, a Nobel Laureate in1918: “A new scientific truth does not gain ground by convincing its opponents, or because they see the light, but, rather because these opponents eventually die and a new generation emerges that is familiar with the idea”.

In the first half of the 20th century, our species was considered of little value in understanding the mechanisms of biological inheritance. Long generations, few offspring, and the impossibility of managed cross breeding were set out as obstacles to cutting edge  work. It was only because of the spectacular development of cellular and molecular methods that the intellectual elite turned to itself, and the study of homo sapiens gained fresh momentum.

In my case specifically, I was awarded my doctorate in 1955 at the University of São Paulo, working with the fruit fly, drosophila; and it was thanks to conversations with Antonio R. Cordeiro that I decided to move to human genetics. In 1956, I went to do a post-doctorate degree at the Department of Human Genetics at the School of Medicine at the University of Michigan, in Ann Arbor, Michigan, in the United States, where another Brazilian colleague, Newton Freire-Maia, was already working. And, to convey an idea of the notable progress achieved by the genetic knowledge of our species, I mention that Newton, on his return from the 1st International Human Genetics Congress held in Copenhagen, Denmark, that year, commented, “Imagine that Fisher (Sir Ronald A. Fisher, one of the leading figures in laying down the basic concepts of genetics and evolution) began the conference saying – man, with 46 chromosomes… – he can’t, it is not yet proved!” and I, in 1957, when I made a series of visits to human genetics centers in the United States and Canada, insisted, in Baltimore, on counting personally under the microscope the number of  chromosomes of an individual of our species.

A book was recently published in the United States by an English scientific journalist, Matt Ridley, in which each chapter corresponds to a chromosome (DNA-protein complex responsible for transmitting genes through cell division). In each chapter (except the last) a gene was chosen for discussing subjects as complex as life, species, fate, intelligence, instinct, health-sickness, sex, immortality and politics. Throughout the book, the basic dialectical question of biological determination versus the history of life is present. Are we a product of our genes or of the environment we live in? The reply, in quantitative terms, will be different depending on the characteristic being examined. What must be emphasized, however, is the importance of the interaction of these two sets of factors.

In 1989, Gustavus Adolphus College in Minnesota, United States, organized a symposium with the thought-provoking title of “The end of science?” and the theme was taken up by John Horgan (see The End of Science. Facing the Limits of Scientific Knowledge in the Twilight of the Scientific Age, Companhia das Letras, São Paulo, 1998). After completing the Human Genome Project, is there anything important left to investigate?  In fact, we are only at the beginning of the genomics era, in which all the genetic material of different species will be identified and compared. To the relief of geneticists and molecular biologists, what the future holds is broad horizons and not dead-end alleys.

Francisco M. Salzano is a professor at the Department of Genetics of the Biosciences Institute of the Federal University of Rio Grande do Sul

Decisive events in the history of (especially Human) Genetics and Molecular Biology

1865Discovery of the laws of heredityG. Mendel
1900Rediscovery of Mendel’s lawsH. de Vries, K. Correns, E. von Tschermak
1902Concept of innate metabolic errorsA.E. Garrod
1906Creation of the termW. Bateson
1901-1908Controversies between followers of Mendel and biometriciansW. Bateson, F. Galton, C. Pearson, W.F.R. Weldon
1908“Hypothesis of the multiple gene” / Behavior of populations with mendelian featuresH. Nilsson-Ehle / G.H. Hardy, W. Weinberg
1910-1935Establishment of the bases of genetics, especially in DrosophilasT.H. Morgan, A.H. Sturtevant, C.B. Bridge
1927Transformation in bacteriaF. Griffith
1944DNA is the transforming agentO. T. Avery, M. MacLeod, M. MacCarty
1949The concept of molecular diseaseL. Pauling
1952The blender experiment – confirmation of the importance of DNA in duplicating genetic materialA. Hershey, M. Chase
1953Establishment of the double helix structure of DNAJ.D. Watson, F.H.C. Crick
1956Start of the Human Cytogenetic eraH.J. Tjio, A. Levan
1961Elucidation of the nature of the genetic codeF.H.C. Crick, L. Barnett, S. Brenner, R.J. Watts-Tobin
1970-to dateApplication of molecular methods to the study of human variabilityVarious
1988-to dateHuman Genome ProjectVarious