The Year of Miracles Part 1
Accounts never, Scientists forever:
High Flying Hopes: Will 2007 be the breakthrough year in genetics?
By Lee Silver
Newsweek International
Oct. 15, 2007 issue - The year 1905 was an annus mirabilis, or miracle year—a rare historical moment in which key flashes of insight suddenly made the field of physics take off in new directions. That was the year Albert Einstein presented four
papers that turned the conventional wisdom about how the universe works, from the infinitesimal realm of atoms to the vast reaches of the cosmos, upside down. During the next several decades, Einstein and a handful of other brilliant physicists went on to shape the 20th century and lay the foundation for all its technological accomplishments.
A century later, the year 2007 is shaping up to be another annus mirabilis. This time biology is the field in transition, and the ideas being shattered are old notions of genes and inheritance.
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 realize, is a fiction.
What's taking its place? 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, 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 that 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 prospects. 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 and heart
disease—could be eradicated. If this sounds outrageously optimistic, so did the promise of eliminating smallpox and polio to previous generations.
Why is all this happening now? What has changed between this year and last? To answer these questions, we need to trace the
story of how mainstream biomedical scientists tried to link the cause of diseases to single genes and, despite early success,
hit a brick wall. Meanwhile, a handful of renegade scientists, pursuing their own pet projects, happened to develop exactly
the intellectual tools needed to break through that wall. These biologists are now the leaders of the new revolution in
biomedical science.
The seeds of our new understanding were first sown in the 1960s, when molecular biologists figured out how genetic
information is organized, regulated and reproduced inside single-cell bacteria. In bacteria, a gene is a discrete segment of DNA that contains the "code" that tells the cell how to make a particular type of protein. Bacterial genes are arranged along a single DNA molecule, one after the other, with only tiny gaps in between. Since all organisms have DNA and work by
essentially the same biochemistry, scientists assumed that a human genome would look like a larger version of a bacterium's.
Clues that something was amiss came quickly with the development of DNA-sequencing methods in the 1970s. The first surprising result was that genes accounted for only 2 percent of the human genome—the rest of the DNA didn't seem to have any purpose at all. Biologists Phillip Sharp and Richard Roberts made things worse with a discovery that won them a Nobel Prize in 1993. If the gene were the basic unit of heredity, the DNA required to make any particular protein should be contained in its corresponding gene. But Sharp and Roberts found that DNA that codes for individual proteins is often split and scattered
throughout the genome.
