How was the Human Genome discovered and When was Genetics invented?

Austrian monk Gregor Mendel discovered the concept of heredity in 1865, launching the field of genetics. In 1953 Francis Crick and James Watson discovered the double helix shape of the DNA molecule that carried all genetic instructions.

The problem was that there were billions of genetic instructions carried on the complete human genetic code, or genome. Understanding it all seemed a physically impossible task. Sequencing the entire human genome was a project 20,000 times bigger and harder than any biological project attempted to that time.

Charles De Lisi at the U.S. Department of Energy (DOE) was the first to gain government funds to begin this monumental process, in 1987. By 1990, the DOE had joined with the National Institutes of Health (NIH) to create a new organization, the International Human Genome Sequencing Consortium (IHGSC). James Watson (of DNA discovery fame) was asked to head the project and was given 15 years to accomplish this monumental task.

At that time, scientists believed that human DNA contained about 100,000 genes spread along 23 chromosomes locked onto DNA’s double helix, held together by over 3 billion base pairs of molecules. Watson’s task was to identify, interpret, and sequence every gene on every chromosome, as well as every one of those billions of base pairs.

Certainly, the ability to identify and sequence individual pairs existed. Watson’s problem was one of size. Using the existing (1990) technology, it would take thousands of years for all existing labs to complete the identification and sequencing of three billion pairs.

Watson decided to start with large-scale maps of what was known about chromosomes and work down toward the details of individual pairs. He directed all IHGSC scientists to work toward creating physical and linking maps of the 23 chromosomes. These maps would provide an overview of the human genome and would include only those few “snippets” of actual gene sequences that were already known.

By 1994 this first effort was complete. Watson ordered IHGSC scientists to map the complete genome of the simplest and best-known life forms on Earth to refine their technique before attempting to work on the human genome. IHGSC scientists chose fruit flies (studied extensively since 1910), e. coli (the common intestinal bacterium), bread molds, and simple nematodes (tiny oceanic worms). In the mid-1990s, work began on mapping the tens of millions of base pairs in these simple genomes.

However, not all biologists agreed with this approach. J. Craig Venter (a gene sequencer at the Institutes of Health) believed that scientists would waste precious years focusing on Watson’s “big picture” and should instead sequence as many specific parts of the genome as they could and piece these individual sequences together later.

A war began between Watson (representing the “top down” approach) and Venter (representing the “bottom up” approach). Accusations and ugly words erupted from both sides at congressional hearings, at funding meetings, and in the press.

Venter quit his government position and formed his own company to develop as much of the genome sequence as he could ahead of IHGSC’s effort. In 1998 Venter shocked the world by announcing that he would use linked supercomputers to complete his sequencing of the entire human genome by 2002, three years ahead of IHGSC’s timetable.

In early 2000 President Clinton stepped in to end the war and merged both sides into a unified genome effort. In 2003 this merged team released their preliminary report, detailing the entire sequence of the human genome. In written form, that genome would fill 150,000 printed pages (500 books, each 300 pages long).

Surprisingly, these scientists found that humans have only 25,000 to 28,000 genes (down from the previously believed 100,000). A human’s genetic sequence is only a few percent different from that of many other species.

Even though the information on this genetic sequence is only a few years old, it has already helped medical researchers make major advances on dozens of diseases and birth defects. Its full value will be seen in medical breakthroughs over the next 20 to 50 years.

If the DNA sequence of the human genome were compiled in books, the equivalent of 200 volumes the size of a Manhattan telephone book (at 1,000 pages each) would be needed to hold it all.