The Human Genome Project
Like the human beings it defines, the human genome is complicated. And the history of its study is as nonlinear as the double helix, as cutthroat as any political campaign and as dramatic as a Hollywood blockbuster. This CultureMap examines that history, from Darwin’s first inklings of genetic coding to the imagined genetic pitfalls of a not-so-distant future.
Intelligent and notoriously ambitious, molecular biologist James Watson earned a PhD at 22; two years later, in 1953, he copublished “Molecular Structure of Nucleic Acids,” the article that spawned the DNA age. Watson’s landmark publication made him a biological luminary, and for the next 35 years, he guided the trajectory of genetic research. By the late 1980s many scientists were pushing for work on the human genome, but Watson was skeptical. No one had yet sequenced even bacterial DNA, and mapping human genes would be extraordinarily expensive—potentially a $30 billion undertaking. “No one who was currently being supported by the government wanted to lose their money for the Human Genome Project,” Watson later reflected.
When he could no longer deny the potential benefits for the fight against genetic diseases, Watson came around and was appointed head of the Office of Human Genome Research, a new National Institutes of Health branch. “It was my job both to pry the cash away from Congress,” Watson explained, “and to ensure it was wisely spent.” He did this by insisting some funding go toward examining the ethical and social implications of genetics study.
Colleagues James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid,” a landmark article unveiling DNA’s double-helix structure, in the April 25, 1953, issue of Nature. They based their findings largely on a diffracted X-ray image of DNA, nicknamed Photo 51, which they had obtained from biophysicist Rosalind Franklin—without her permission. They also used much of Franklin’s unpublished data.
Along with DNA’s now commonly known structure, Watson and Crick uncovered the concept of base pairs: the idea that certain molecules, as defined by their particular nitrogen-containing bases—adenine (A), thymine (T), guanine (G) and cytosine (C)—stretch between the twin helices to match with their corresponding molecules. That is, A can match only with T, and G with C, as one helix is the inverted copy of its twin. The dual-corkscrew structure illuminated for the first time how molecules could replicate (match up in a specific order) to build an entire complex living organism. In 1962 the two men shared a Nobel Prize for their findings. Franklin died of ovarian cancer in 1958, and for decades received no more credit for her contribution than she had in the original journal article.
James Watson’s groundbreaking work on the human genome inspired Gattaca, a 1997 science-fiction thriller by writer-director Andrew Niccol examining the sociological dangers of genetic modification. The titular aerospace corporation, which employs only the genetically perfect as astronauts, derives its name from abbreviations for the DNA base pairs Watson discovered: G, A, T and C.
Watson loved the film, and his 2009 book DNA: The Secret of Life, devotes part of the chapter “Our Genes and Our Future” to its plot, characters and stars. Watson writes, “Few, if any, of us would wish to imagine our descendants living under the sort of genetic tyranny suggested by Gattaca.” Yet he also harbored fantasies of a genetic utopia. In the documentary DNA (2003), he admits, “The lower 10 percent, who really have difficulty…what’s the cause of it? A lot of people would like to say, ‘Well, poverty, things like that.’ It probably isn’t. So I’d like to get rid of that, to help the lower 10 percent.” Genetically enhanced children, he adds, “are going to…dominate the world.” To some, the idea is exciting; to others, it is as disturbing as this haunting line from Gattaca: “We now have discrimination down to a science.”
James Watson began the Human Genome Project in 1990, only to resign in 1992 after political differences with National Institutes of Health director Bernadine Healy over who should patent genetic material—the NIH or private research companies (Watson had financial ties to the latter). Watson’s eventual successor as director was Francis Collins, a geneticist notable for developing landmark gene-hunting techniques and isolating the genetic marker for cystic fibrosis. Collins saw the project through to completion in 2003.
Publicly the men advertised mutual respect: Watson wrote that Collins brought to the project “a scientific excellence as well as a spiritual dimension singularly lacking in his predecessor.” Collins described Watson as “the unrivaled rock star of biology” in those early days of genomic study. Yet the men’s personalities were vastly different, if equally controversial: Collins, regarded as a compassionate doctor, became a Christian while in medical school and is often criticized for being too religious for a scientist of his status. Solipsistic Watson, who calls himself a Catholic “escapee,” has drawn criticism too—for his insensitive, prejudicial suggestions that certain groups of people would be better off with genetic modifications.
A seminal publication in biology, Charles Darwin’s On the Origin of Species outlines the theory of evolution: An organism’s traits adapt to changes over time for the long-term benefit of its species. James Watson and Francis Crick’s 1953 article in Nature, “Molecular Structure of Nucleic Acids,” was another game changer, especially when applied to Darwin’s ideas. Although scientists had long accepted the concept of genetically determined traits, the actual genetic code remained mysterious nearly a century after Darwin’s revelation.
By discovering DNA’s structure, Watson and Crick cracked that code, enabling researchers to examine the mechanisms behind evolution. Molecular biologist Sean Carroll explained, “You can’t necessarily see the change happening…, but you can see that if you change that nucleic acid base right there in that gene, at that particular point in embryonic development, that animal is darker. If you change those three bases over there, that limb is longer. This is the fundamental basis of evolution: changes in DNA.”
In the past 50 years Nature has published numerous articles relating evolution to DNA, including most papers by the Human Genome Project. As the most widely cited scientific journal, Nature is a touchstone for evolutionary study, like Darwin’s book before it.
When Francis Collins became head of the Human Genome Project and later of the National Institutes of Health, many scientists expressed concern that his strong Christian beliefs would undermine his work—but of course, this was nothing new. The rift between religion and science existed “long before Darwin and his Origin of Species first appeared,” Collins writes in his 2006 book The Language of God. In fact, Darwin was a religious man, “intensely insecure about his theory of evolution,” according to Collins—which some historians speculate is the reason for Darwin’s 20-odd-year delay between developing his theory and publishing his magnum opus. In a letter to a friend, Darwin wrote, “I own that I cannot see…evidence of design and beneficence.… I can see no reason why a man, or other animal, may not have been aboriginally produced by other laws and that all these laws may have been expressly designed by an omniscient Creator…. But the more I think, the more bewildered I become.”
To explain how religious belief can harmonize with evolutionary fact, Collins expands upon Darwin’s argument of design by law. He calls DNA “God’s instruction book,” saying of the HGP’s work, “The language of God was revealed.”
The screenplay for 1997’s Gattaca ends with foreboding: “In a few short years, scientists will have completed the Human Genome Project…. After 4 billion years of evolution…we have now evolved to the point where we can direct our own evolution.” Following this is a list of influential people who, under the film’s dystopian laws, would never have been born. Renowned theoretical physicist Stephen Hawking, who suffers from the debilitating genetic disease amyotrophic lateral sclerosis, is one of these.
In The Language of God, Francis Collins describes “chilling” comments Hawking made to advocate “that it was time for humanity to take charge of its evolution” through genetic “self-improvement.” Collins has taken pains to differentiate his HGP work from the science-fictional practices in Gattaca and denounced private genetics companies for treating “fundamental information about ourselves” as a commodity the private sector owns. Yet he has lofty HGP goals. By making information about DNA sequencing “freely available in the public domain” he hopes one day to prevent genetic variations linked to such infirmities as heart disease, cancer, obesity, diabetes and even psychiatric illnesses. The line between improving lives and engineering perfection remains blurred, even for vocal critics of the ideal expressed in Gattaca.
Filmmaker Andrew Niccol has a knack for tapping into topical fears. His scripts for The Truman Show and Simone, written at the dawn of the digital age, explore the dangerous intersection of reality and virtual reality. In 1997, six years before the completion of the Human Genome Project, Niccol’s Gattaca effectively encapsulated society’s fears about genetic technologies, instantly becoming a cultural touchstone on the subject. The film is set in a futuristic dystopian society where an oligarchy persecutes anyone with a less-than-perfect genetic makeup.
Since 1997 the term human genome has appeared in the Congressional Record 526 times, with the highest frequencies occurring in the sessions right after Gattaca’s release. The U.S. Congress has dealt with a range of issues related to the HGP, many of which are represented in the film—from control of genomic information by public and private institutions, to the ethics of using DNA databases in crime fighting, to the regulation of genetic experimentation. Perhaps the most notable instance is the Genetic Information Nondiscrimination Act of 2008, banning health insurance companies and employers from using genetic information to deny coverage or employment. The characters of Gattaca should be so lucky.
In 2000, before leaving the White House, President Bill Clinton grandly announced the completion of the Human Genome Project. But the work wasn’t truly finished until 2003, when project head Francis Collins declared, in the journal Nature, that the HGP had accomplished its 13-year mission to “identify approximately 20,000–25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA, store this information in databases, improve tools for data analysis, transfer related technologies to the private sector and address the ethical, legal and social issues that may arise from the project.”
Collins’s team completed the HGP two years ahead of schedule—to coincide with the 50th anniversary of James Watson and Francis Crick’s landmark Nature article, which unveiled the structure of DNA. On April 25, 2003, to celebrate the scientific work that sparked half a century of research, Congress passed a bill establishing DNA Day, a holiday to be observed with genetics-themed school activities, essay contests and federally funded cash prizes. The hope is to inspire the next James Watson, Francis Collins or Rosalind Franklin to grow up to pioneer the next phase of human genetics research.