In June 2000 scientists joined U.S. President Bill Clinton at the White House to unveil the
Human Genome Project's "working draft" of the human genome—the full set of DNA that makes us human (
quick human genetics overview).
As the tenth anniversary of that achievement approaches, scientists weigh in on the scientific discoveries the Human Genome Project enabled, as well as some hopes and predictions for future advances that could be made using the project's data.
BREAKTHROUGHS POWERED BY THE HUMAN GENOME PROJECT
1. Democratized Data
Coordinated by the U.S. Department of Energy and the National Institutes of Health (NIH), the Human Genome Project formally lasted from 1990 to 2003. The project helped pioneer the now common practice of making scientific data freely available online.
(Related:
"'Eco Hubble' to Bring Nature Data to the Public.")
This open model of research has enabled researchers to make discoveries much more quickly than in the past, said
Francis Collins, NIH director and former leader of the U.S.-government effort to sequence the human genome.
"For example, the search for the cystic fibrosis gene finally succeeded in 1989 after years of effort by my lab and several others, at an estimated cost of U.S. $50 million," Collins writes in an opinion piece published in this week's issue of the journal
Nature.
"Such a project could now be accomplished in a few days by a good graduate student. ... ," he writes. All the budding geneticist needs, Collins says, is the Internet, some inexpensive chemicals, a thermal cycling machine to amplify specific DNA segments, and access to a DNA sequencer, which "reads" DNA via light signals.
2. Added DNA to Human-Origins Tool Kit
The Human Genome Project has proven to be a valuable new tool for studying human origins and the history of our species' migrations, said
Mark McCarthy of the University of Oxford in the U.K., who studies the genetic causes of diabetes and obesity.
"We've learned how young a species we are and how similar so many of us are, particularly those populations that came out of
Africa 70,000 years ago"—such as the ancestors of modern Europeans or East Asians or South Asians—McCarthy said.
The genetic data largely back up theories derived from archeological and linguistic studies, such as the idea that ancestors of many modern human populations originated in Africa, he added. (See
"Massive Genetic Study Supports 'Out of Africa' Theory.")
Furthermore—by working under the assumption that the more closely related different human populations are to one another, the more similar their genomes will be—scientists have been able to roughly chart out the path that humanity took as it spread around the world.
3. Snipped Away at Diseases' Prehistoric Origins
The Human Genome Project set a foundation for later efforts such as the International HapMap Project, which aims to uncover single nucleotide polymorphisms, or SNPs ("snips").
SNPs are differences in the lettering of genes among members of the same species. The written language of DNA uses four "letters," or nucleotides: A, T, C, and G.
HapMap is a catalog of common SNPs that occur in human beings. SNPs that lie next to each other on a chromosome and are inherited together are called haplotypes; clusters of related haplotypes are called haplogroups.
SNPs can greatly influence our susceptibility to certain diseases, such as cancer, heart disease, and diabetes, scientists say. (Find out how an
SNP-laden hairball helped reveal the face of a 4,000-year-old human.)
Geneticist Spencer Wells, who leads the National Geographic Society's
Genographic Project, called HapMap "the biggest payoff of the Human Genome Project so far." (The National Geographic Society owns National Geographic News.)
HapMap "revealed the relatively high frequency of genetic diversity that exists across the entire genome. Using that data, scientists were able to start looking at disease associations at a genome-wide level," said Wells, who is also a National Geographic
explorer-in-residence.
This is important because scientists are finding that many diseases have multiple gene influences.
"For the really interesting diseases, you've got a lot of genes that have relatively low effect" by themselves, Wells said.
4. Found Lack of Junk in Our Genetic Trunk
Before the Human Genome Project, some scientists had estimated the known three billion or so DNA letters combined to form a hundred thousand or more genes.
"That seemed sensible, because we're such big, complicated organisms," said
Christopher Wills, a biologist at the University of California, San Diego.
"But the amazing thing is that there are much fewer genes in the human genome than expected"—only about 20,000 to 25,000—"which means that each gene has to be very sophisticated in what it does," Wills said.
Because the number of DNA letters per gene is limited, the new, lower gene count made clear that about 98.5 percent of our DNA has nothing to do with genes—junk DNA, some called it.
(See
"First Decoded Marsupial Genome Reveals 'Junk DNA' Surprise.")
But even junk DNA strands—long seen as useless or as relics of vestigial genes—are proving they hold a few gems.
"The part of [DNA] that doesn't code for proteins, which is about 98.5 percent of it, turns out to be much more rich in functional characteristics than I think a lot of people had imagined," NIH's Collins told National Geographic News.
"There doesn't seem to be much reason to use the word 'junk DNA' anymore," Collins added.
5. Supercharged Genetic Research
The Human Genome Project has helped foster the creation of newer, faster, and cheaper methods of gene sequencing, said
George Church, who heads the Personal Genome Project at Harvard University.
That's because the rough draft of the human genome that resulted from the Human Genome Project serves as a reference against which the data from new sequencing methods can be compared.
"It's like doing a jigsaw puzzle," Church explained. "If you've got the final picture on the cover of the box, ... you can say, This little piece goes here."
PREDICTIONS FOR THE NEXT TEN YERS
1. Science Will Pinpoint What Makes Us Homo Sapiens
In the near future, scientists will be able to compare our genome against those of our evolutionary cousins, such as chimpanzees and Neanderthals, to get a clearer sense of which genes are involved in making us
Homo sapiens, the University of California's Wills said.
"The thing I'm really looking forward to is finding out how we differ from our close relatives, what has driven us toward becoming human beings, and in particular, which genes are responsible for our astonishing talents," Wills said.
NIH's Collins called the recent
success at partially sequencing Neanderthal DNA "fascinating."
"I think most people ten years ago would not think it would be possible to reconstruct an accurate rendition of a sequence of Neanderthals," Collins added, "and yet we're pretty close to that."
2. Gene Therapy Will Cure Diseases
Gene therapy—curing ailments by replacing faulty copies of genes with normal ones—will finally become a reality, likely within the next decade, the University of California's Wills said.
(Related:
"Color-blindness Cured by Gene Injection in Monkeys.")
"The big problem has been, How do you get the genes to the cell?" he said.
Scientists have been using viruses to "infect" animals' DNA with new genes, Wills noted, "and that's dangerous.
"But I think a breakthrough is going to be happening fairly soon. When it does, it's going to be very exciting."
(Also see:
"How 'Gene Doping' Could Create Enhanced Olympians.")
3. The Very Meaning of "Gene" Will Change
The traditional definition says a gene is a region of DNA that encodes for a protein.
But in recent years, scientists have discovered stretches of so-called junk DNA that don't make proteins but are nonetheless important.
For example, some regions of DNA appear to hold instructions for producing a DNA-like, but non-proteinaceous, molecule type called double-stranded RNA.
"These double-stranded RNAs"—part of the body's RNA interface or RNAi—"turn out to be very strong regulators of the way that genes function," Wills said. (Find out why the
discovery of RNAi led to a Nobel Prize.)
Some double-stranded RNA, for example, can "silence" genes by preventing their protein products from being produced. They do this by binding to and blocking a messenger molecule in the protein-creation pathway, called messenger RNA.
Wills estimates that if bits of double-stranded RNA were counted as genes, they would double the estimated number of genes in the human genome.
"As far as I'm concerned, I'm happy to call them genes without worrying about semantics," he said.
NIH's Collins agreed. "I think we're at a bit of a semantic difficulty here, in terms of deciding what to consider a gene," he said. "Genes are units of inheritance that need not be thought of in such simplistic ways anymore."
4. Personal Genomes Will Spawn Made-to-Measure Drugs
Thanks to improving technology, within the next five years a person should be able to have his or her entire genome sequenced for about a thousand U.S. dollars, many experts say.
Soon after, that figure could drop as low as a hundred dollars, the Genographic Project's Wells said. "I could imagine a time, ten years from now, where it could get down that cheap."
NIH's Collins said the pace of technological innovation has been dizzying to watch.
"I thought we would get to this point, but I didn't think we would get here so quickly," he said.
The cost of sequencing a human genome "has come down by a factor of more than 10,000. That means DNA sequencing is moving forward more quickly than that classical example of exponential growth, which is Moore's law from computers." Moore's law speculates that the processing power of computer chips doubles every two years.
Collins envisions a day soon when everyone's genome will be sequenced and included as a routine part of their medical records.
By "knowing what you're at risk for and individualizing your preventative medicine plan," doctors will be better able to treat their patients, Collins said.
The era of personal genomes will also be a boon to pharmacogenomics, the science of tailoring drugs to an individual's genetic makeup.
5. Personality Will Move From Art to Science
As scientists learn to better understand the information contained in our genomes, they will get better at predicting how genes influence the development of physical and mental traits and even behaviors.
In the distant future it may be possible to look at the genome of a human—or a close human relative—and roughly deduce not only what she looked like, but, for example, how she acted.
"Will we ever be able to do it with complete confidence? I suspect not, and I rather hope not," the University of Oxford's McCarthy said.
"But I do suspect that by the time we've finished this journey that we've started on ... we'll be able to do better than we're doing at the moment."
National Geographic Explorer-in-Residence Robert Ballard, best known for his discovery of the R.M.S. Titanic, thought he knew everything about his ancestry, with a genealogy that traces back to the British Isles and Holland. While most of his DNA agrees with this story, he learned something unexpected from his Geno 2.0 results—his genome is about 2% Oceanian, connecting him to the first seafarers who settled the islands off the coast of southeast Asia around 50,000 years ago, probably via the Dutch side of his family. 
Yawn.