How Did the Human Genome Project Begin?

mapping human gene sequence took 15 years of work

By Jonny Lupsha, Wondrium Staff Writer

In 2003, the National Institutes of Health published a final draft of the human genome. It was a project that had its roots 30 years earlier with a British biologist. How did the Human Genome Project begin?

Cells under human DNA system
Photo by Billion Photos / Shutterstock

According to the National Human Genome Research Institute, a genome is the entire set of DNA instructions found in a cell. This set of instructions contains more than 3 billion base pairs of DNA nucleotides. In April 2003, the National Institutes of Health published a final draft of the 3 billion base pairs as they occur in humans in their proper sequence after using DNA from a man in Buffalo, New York.

Last week, scientists unveiled a much more diverse update to the human genome, which used DNA from 47 people of varying ethnic backgrounds. Calling it the “pangenome,” its goal is to provide more context and a thorough look at the differences between humans.

What are the Human Genome Project’s origins? In his video series Unlocking the Hidden History of DNA, science writer Sam Kean recalls the early details of this massive scientific endeavor.

How Were Genomes First Mapped?

Genetic base pairs are complementary rungs on the double helix ladder made up of adenine, cytosine, guanine, and thymine—shortened to A, C, G, and T.

“The Human Genome Project traces its pedigree to the 1970s, when a British biologist and previous Nobel Prize winner named Frederick Sanger invented a method to sequence DNA,” Kean said. “That is, he figured out a way to record the order of the As, Cs, Gs, and Ts in DNA.”

In order to sequence DNA, Sanger first heated the strands until they separated. Next, he broke the strands into smaller fragments. Finally, he used individual bases to build complementary strands to the original fragments. However, he used special bases with radioactive atoms in them so they’d attach to their complementary strands.

This meant he could tell whether it was an A, C, G, or T base causing the radiation and note its complementary half in the DNA strand.

“Unfortunately, Sanger had to read these bases one by one, a tedious process,” Kean said. “Nevertheless, the process allowed him to sequence the full genome of a virus—a single strand of nearly 5,400 bases, grouped into 11 genes. This was the first full DNA genome ever sequenced, and the work won Sanger his second Nobel Prize, for chemistry, in 1980.”

How Did the Human Genome Project Begin?

Six years later, two biologists in California expanded on Sanger’s work and used fluorescent versions of A, C, G, and T that produced a different color of light when struck by a laser beam. This helped speed up the work of sequencing genomes, especially when run by a computer.

“In April 1987, the U.S. Department of Energy started the world’s first human genome project, a proposed $1 billion effort,” Kean said. “Why the Department of Energy? Well, because radioactive exposure from nuclear bombs or power plant accidents can damage DNA, and officials were interested in the health consequences. They considered sequencing an extension of that work.”

About 18 months later, in September 1988, the National Institutes of Health (NIH) became involved in the endeavor. The NIH set up a rival project and vowed to map the entire human genome in 15 years. As their project chief, they hired James Watson, who had won a Nobel Prize in 1963 for his work on the double helix structure of DNA.

Initially, many scientists were reluctant to work on the project for several reasons. They thought it reduced science to unimaginative strings of letters and they bristled at the idea of not controlling the direction of their own research.

“But Watson did a masterful job of calming his colleagues’ fears, and he helped NIH wrestle most of the project away from the Department of Energy,” Kean said.

Unlocking the Hidden History of DNA is now available to stream on Wondrium.

Edited by Angela Shoemaker, Wondrium Daily