We now have the possibility of achieving all we ever hoped for from medicine.
—UK Science Minister Lord Sainsbury
June 26, 2000
On the day of the completion of the
mapping of the human genome
The earth is not flat, pellagra is not caused by a germ, and the sun does not revolve around the earth! Unfortunately science advances one funeral at a time. Protectors of a particular scientific belief or theory (particularly vicious regarding medical theories) will go to the extremes of blackballing, such as was the case with reactions to the theories of the etiology of cystic fibrosis (Wallach) and the practice of eugenics (Galton), and when there were executions for practitioners of sorcery (Joan of Arc). There have been uncountable murders and wars to thwart competing information, theories, and truths.
When “the” existing “truth” is dethroned, the champions of “the new truth” become the ruthless defenders of “the” new “truth,” thus creating a death-watch for the next funeral for new champions to advance science.
Perhaps one of the most clear thinking epigeneticists is Nessa Carey, a PhD virologist who was trained at the University of Edinburgh and was a senior lecturer at Imperial College in London. In her book The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance, she points out that even experts in the genome projects have been frustrated with the lack of usefulness of what they have mapped out.
The genomes of more than 180 species have been sequenced since 1995. Genome sequencing reads and records the order of DNA nucleotides in a genome: the pattern of the base pairs A-C and G-T that comprise an individual’s DNA. The 1977 genome sequencing project of Frederick Sanger, the great modern geneticist, drove the creation of the Human Genome Project by developing techniques of amino acid sequencing.
Sangers’s work that identified the amino acid sequencing of insulin in 1951 gave people the false hope that diseases thought to be genetically transmitted could be prevented and cured through “genetic engineering.”
The Sanger’s sequencing technique involves separating fluorescent-labeled DNA fragments based on the length of a polyacrylamide gel. The base at the end of each fragment is identified by how it responds to a specific dye.
Sanger used his technique to sequence the DNA of the bacteriophage fx174, a viral genome with 5,368 base pairs. He discovered that there was overlap among the genes in some areas with respect to coding, a finding that enabled geneticists to analyze longer strands of DNA more rapidly and with greater accuracy than earlier efforts. For his work, in 1980 Sanger was awarded his second Nobel Prize in chemistry, which he shared with Walter Gilbert and Paul Berg. Sanger had won his first Nobel Prize in 1958 for his work in identifying the structure of proteins.
The purpose of all of this genetic research was to provide the tools necessary to correct diseases thought to be genetically transmitted. The process to produce these genetic tools is referred to as “genetic engineering.”
Genetic engineering, also referred to as genetic modification, involves direct manipulation of an organism’s genetic material. It employs recombinant DNA, in which two or more genetic sequences are combined in a way that would not commonly occur in nature.
The Origin of genetic engineering is based on the work of American biochemists Herbert Boyer and Stanley Cohen, who developed the technique of DNA cloning.
The first genetically engineered organisms were bacteria (1973) and mice (1974). More recently, biologists have used genetic engineering principals in research, biotechnology, medicine, and other fields.
The process involves collecting the appropriate DNA material and copying it to ensure that the genes will express themselves and the desired genetic material is placed into a host genome.
The Human Genome Project (HGP) began in 1990 under the leadership of James Watson, the American molecular biologist, who had along with Francis Crick won the Nobel Prize in 1962 for elucidating the structure of the DNA double helix, and later under the leadership of an American physician-geneticist Francis Collins.
The HGP is the international effort assembled to determine the genetic sequence of the approximately three billion base pairs in human DNA and to understand the functions of its 20,000 genes.
Genes are the units of heredity and are found as actual physical structures that are found on stretches of DNA and function by producing or replicating proteins or an RNA molecule that has a specific enzymatic or structural function.
To accelerate the identification of the human genetic sequence, the computer augmented genome was broken up into smaller fragments to be worked on by different investigators. These small fragments were inserted into bacteria which would then reproduce them for a standard source and unlimited supply or “library” of these cloned DNA fragments. The next step was to assemble the resulting fragments into the complete whole DNA strands.
The biggest revelation was that except for identical twins, each human genome differs—Houston, we have a problem! The HGP participants had incorrectly anticipated that there would be a “one genome fits all” result of their study. The idea was that if someone had defective DNA, they could come to the lab and get a DNA transplant much in the same way that one can receive a heart, liver, kidney, or bone marrow transplant.
Again, totally unexpected results were that less than one percent of the human genome’s DNA codes for protein reproduction. The number of genes in humans is now known to fall somewhere in between the number of genes found in grapes (30,400) and the number of genes found in chickens (16,700). And almost half of the human genome is comprised of interchangeable DNA fragments that move around, on and in between chromosomes.
Collins (the physician) reported in 2001 that the HGP had assembled the majority of the human genome map: “It’s a history book: a narrative of the journey of our species through time. It’s a shop manual: an incredibly detailed blueprint for building every human cell. And it’s a transformative textbook of medicine with insights that will give health-care providers immense new powers to treat, prevent, and cure disease.”
A more complete genome sequence that was announced in 2003 is considered by physicians and the genetic industry, “to be a watershed moment in the history of civilization.”
In November 2012 a report from the $120 million 1000 Genomes Project announced that the complete mapping of the DNA material from more than 1,000 humans from 14 population groups in Europe, Africa, East Asia, and the Americas had been achieved. The project involved 700 scientists from laboratories in the United States, Canada, China, Japan, Nigeria, and Kenya.
The report identified 38 million variations in the chemical letters of DNA that make up each of the average person’s 23,000 plus genes and the DNA regions that control them—an estimated 98% of all the human variations in the world. This immense catalogue of the human genetic code is equal to 16 million file cabinets or 30,000 DVDs.
In general, all humans share approximately 99% of the DNA code that controls development, health, personality, and other traits. However, the common genetic variations that most people share account for only a small percentage of the risk for diseases thought to be heritable.
Genetic variation among people refers to the differences in the order of chemical units (nucleotides), identified by the acronyms A, G, C, and T, which would be the equivalent of the three billion letters of the DNA in the human genome.
“The biggest question is trying to figure out how much of this variation is meaningful,” said Dr. Aravinda Chakravarti, an expert in disease genomics at Johns Hopkins University in Baltimore who is part of the genomic project, “much of it may make very little difference.”
The report also shows that there are differences in people in various parts of the world or even different cities. “The stuff that is rare—present in one of 100 people—in the United Kingdom is different from the stuff at that frequency in Holland or Italy,” said Dr. Gilean McVean at Oxford University in England.