Ever since 1900, when Gregor Mendel’s work on peas and inheritance was rediscovered, scientists have regarded the “gene” as the fundamental unit of heredity (just as the atom was regarded as the bedrock of pre-Einsteinian physics). Crick and Watson’s discovery of the DNA double helix as the carrier of hereditary information did little to disturb the status quo. In recent months, however, a perfect storm of new technology and research has blown apart 20th-century dogma. The notion of the Mendelian gene as a unit of heredity, scientists now realise, is a fiction.
Many scientists now believe that heredity is the result of an incredibly complex interplay among the basic components of the genome, scattered among many different genes and even the vast stretches of “junk DNA” once thought to serve no purpose. Biology has been building up to this insight for years, but some big puzzle pieces have now fallen into place. Once scientists abandoned their preconceived notions of genes and looked instead at individual DNA “letters” in the genome—the four bases A, C, T and G— they immediately began to see cause-and-effect connections to myriad diseases and human traits.
The result of this seemingly modest conceptual breakthrough has been a torrent of new discoveries. In five months this year, from April through August, geneticists at the Harvard/MIT Broad Institute, founded by Eric Lander; at deCODE Genetics in Iceland, founded by Kari Stefansson, and several other institutions have published papers suggesting that the key to a deeper understanding of the human genome may finally be in hand. These scientists have identified specific alterations in the sequence of DNA that play causative roles in a broad range of common diseases, including type 1 and type 2 diabetes; schizophrenia; bipolar disorder; glaucoma; inflammatory bowel disease; rheumatoid arthritis; hypertension; restless legs syndrome; susceptibility to gallstone formation; lupus; multiple sclerosis; coronary heart disease; colorectal, prostate and breast cancer, and the pace at which HIV infection causes full-blown AIDS. Unlike so many previous “disease gene” discoveries, these findings are being replicated and validated. “The race to discover disease-linked genes reaches fever pitch,” declared the leading British science journal Nature. Its American counterparts at Science chimed in: “After years of chasing false leads, gene hunters feel they have finally cornered their prey. They are experiencing a rush this spring as they find, time after time, that a new strategy is enabling them to identify genetic variations that likely lie behind common diseases.” That the world’s top two scientific journals still use the old language of “genes” to describe these discoveries shows how new the new thinking really is.
These findings are just a prelude to what’s shaping up as a true conceptual and technological revolution. Just as physics shocked the world in the 20th century, it is now clear that the life sciences will shake up the world in the 21st. In a handful of years, your doctor may be able to run a computer analysis of your personal genome to get a detailed profile of your health. This goes well beyond merely making predictions. A new technology called RNA interference may also allow doctors to control how your DNA is “expressed,” helping you circumvent potential health risks. Many common diseases that have preyed on humans for eons—devastating neurological conditions such as Alzheimer’s, Parkinson’s, cancer—could be eradicated. If this sounds outrageously optimistic, so did the promise of eliminating smallpox and polio to previous generations.
