THE HUMAN GENOME PROJECT
Recent columns of Armchair Genealogy have provided basic background information of DNA, its discovery, significant application of those discoveries that further our use of the knowledge, and a very basic Glossary organized not alphabetically but logically to provide a framework for discussion. This column will focus on the Human Genome Project.
What prompted the creation of the project? How was it funded? What were its goals? Who was involved? And, not the least important, what does the Project's findings mean to us as family researchers?
First, we should revisit important milestones leading to mankind's discovery and desire to better understand DNA.
Historical Advances that Led to Discovery of DNA:
The discovery of DNA, the foundation for creation, had its roots in theory. In 1831, Charles Darwin joined a scientific expedition that studied fossils. His inspection of these fossils aroused his interest, specifically, what caused the apparent improvement in structure from one generation to the next? By 1859, Darwin could articulate his theory: which could be called 'survival of the fittest'. Darwin theorized some core element caused the change: the creature best suited to survive in its habitat developed a mutation that could be passed on to the next generation, thus changing the entire species until the next adaptation occurred in response to some new challenge.
This theory was amplified by the studies of an Augustinian monk, Gregor Mendel. Mendel undertook exhaustive experiments of pea plants in a continuous study begun in 1859. Through his studies, Mendel defined the terms of dominant and recessive traits in genetic transformation.
"In his 1866 published paper, Mendel described the action of 'invisible' factors in providing for visible traits in predictable ways. We now know that the 'invisible' traits he had identified were genes."
In 1869, a groundbreaking discovery was made by Friedrich Meischer, a Swiss physiological chemist seeking to isolate the protein substances comprising white blood cells. In the process, he found a substance with chemical properties quite different in composition to those he had been studying. He described it as having "very high phosphorus content and a resistance to protein digestion." The substance was, in fact, deoxyribonucleic acid - DNA.
In 1900, Mendel's theory of dominant and recessive traits being predictable but guided by some as yet unidentified underlying factor generated studies by Hugo DeVries, a Dutch botanist and geneticist; by Carl Erich Correns, German botanist and geneticist; and Eric Tschermak von Seysenegg, an Austrian botanist. Using his experiments as their basis, each reported hybridization experiment results similar to his findings.
By 1902, Mendel's studies found substantiation in the efforts of Sir Archibald Edward Garrod, an Oxford educated physician. In his studies of families beset with Alcaptonuria, Garrod ascribed the high incidence of familial inheritance of this rather rare disease to "inborn errors of metabolism." Garrod discussed his beliefs with William Bateson, a leading proponent of Mendellian theory. When Garrod published his scientific study entitled 'The Incidence of Alcaptonuria: A Study in Chemical Individuality' in 1902, that marked the first time recessive inheritance traits in humans were ascribed to a molecular basis of inheritance.
By 1944, scientists understood more about genetics. They had accepted the fact genes formed the "discrete units of heredity" and that they generated "enzymes that controlled metabolic functions." Oswald Avery, a Canadian-American scientist and medical researcher, discovered mixing a harmless form of live pneumococcus with an inert but lethal form transformed the harmless bacteria into a deadly organism.
In concert with Colin MacLeod and Maclyn McCarty, Avery carried out endless experiments in purifying collected bacteria. The remaining substance was deemed neither protein nor carbohydrate, but a nucleic acid, ultimately identified as DNA. The study they published named DNA as the resulting in their conclusion: "the nature of DNA is the transforming principle."
Avery's findings changed the course of study for another scientist, Erwin Chargaff. He changed his focus to in-depth analysis of the chemistry of nucleic acids. He first developed a method of analyzing that identified the nitrogenous components and sugars of DNA from different species. His research led to two major findings, published by him in 1950, known today as Chargaff's Rules: 1) in any double stranded DNA, the number of guanine units is equal to the number of cytosine units and the number of adenine units is equal to the number of thymine units, and 2) the composition of DNA varies between species.
These Rules have been indispensable in further studies of DNA.
1952 was of immense importance in the study of DNA. Rosalind Franklin, a British woman who achieved a doctorate in physical chemistry from Cambridge University then went on to learn x-ray diffraction techniques. In 1951, working with scientist Maurice Wilkins and student Raymond Gosling, she was able to produce two sets of high-resolution photographs of DNA fibers. From these photos, Franklin calculated the dimensions of the strands and deduced the phosphates were on the outside of what was probably a helical structure. Between 1951 and 1953, Rosalind Franklin came ever closer to identifying the structure of DNA. That discovery, though based upon her photographs and basic conclusions, was attributed to James Watson and Francis Crick. The duo set out to study the structure of DNA at Cavendish Laboratory at Cambridge University in 1951. Through use of x-ray data and model building, they solved the puzzle that had baffled scientists for decades. Their paper, published in April 1953 resulted in them being awarded the Nobel prize in 1962 for physiology or medicine along with Maurice Wilkins (the scientist with whom Franklin had worked.)
Additional advances were made in the study of DNA, techniques advancing the accessibility of actual DNA sequences, and discoveries of genetically linked diseases. All these made more and more scientists eager to delve into the study of DNA.
"Despite the fact that her photographs had been critical to Watson and Crick's solution, Rosalind Franklin was not honoured, as only three scientists could share the prize.
One significant discovery occurred in the late 1960s and early 1970s when stains such as Giemsa were found to "bind to chromosomes in a non-uniform fashion, creating bands of light and dark areas. The invention transformed the discipline, making it possible to identify individual chromosomes, as well as sections within chromosomes, and formed the basis of early clinical genetic diagnosis."
These advances made huge ripples in the scientific community. Suddenly the study of DNA was in the forefront of news. Everyone was now fascinated by the frequent news of the latest discoveries tying genetic abnormalities to known human frailties and diseases: Down Syndrome, Huntington's Disease, breast cancer. Interest was aroused in having a government-funded project to advance the demystification of the basis of life.
Timeline of The Human Genome Project:
1990: The Human Genome Project began and was funded by the US Department of Energy and the National Institute of Health. It was recommended in 1988, but officially started in 1990. Multiple purposes existed for the initiation of this project, not only the advancement of medicine, but for other purposes such as the detection of mutations that nuclear radiation might cause.
"The project's goals included: mapping the human genome and determining all 3.2 billion letters in it, mapping and sequencing the genomes of other organisms, if it would be useful to the study of biology, developing technology for the purpose of analyzing DNA and studying the social, ethical and legal implications of genome research."
Next month's column will address the following subjects:
Significant Findings of The Human Genome Project:
What Remains to be Discovered?