The great DNA letdown

    This is science as a biopic: the stars are four regular guys named A, T, C, and G. Like the mop-top Beatles who came from Liverpool nearly 50 years ago, this Fab Four are the superstars of our era, which has been dubbed the Age of Genomics.

    Since scientists announced the sequencing of nearly every A, T, C, and G in humans a decade ago, their influence has permeated movies, comics, books, newscasts, universities, lecture halls, and the blogosphere. Governments and life science companies large and small have lavished hundreds of billions of dollars on genetic research and development.

    Thousands of scientists and hundreds of companies — including many in the Fortune 500 — still labor to tease out the secrets of these often elusive sequences of genetic code tucked inside of our cells, and how they impact disease, behavior, and life itself.

    Fans of the Human Genome Project have compared it to the Apollo Program, and called it "the book of life." Not since Einstein's E = mc² had science been so sexy and exciting, with just a tinge of danger.

    But 10 years later, the accomplishments, in terms of human health, have failed to live up to the hype, according to top scientists writing in Nature.

    "Some major advances have indeed been made," opines the lead editorial in Nature, "powerful new drugs have been developed for some cancers; genetic tests can predict whether people with breast cancer need chemotherapy; the major risk factors for macular degeneration have been identified; and drug response can be predicted accurately for more than a dozen drugs. But it is fair to say that the Human Genome Project has not yet directly affected the health care of most individuals."

    Nor has it produced the raft of products (and profits) expected in 2000 when President Bill Clinton stood in the East Room of the White House with leading scientists to announce the near completion of the Human Genome Project. "With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal," he declared.

    Biotech companies like Celera Group (CRA), Millennium Pharmaceuticals, Human Genome Sciences (HGSI), and deCode Genetics raised billions of dollars in the years just before and after the White House ceremony. They promised not only a raft of new drugs based on a deeper understanding of genetics but also billions of dollars in revenues. Big Pharma companies invested heavily in these companies and in their own genomics programs.

    The genome allure came in part from the simplicity and elegance of the code. Unlike most of biology, which is complicated, sloppy, and quite literally wet and slimy, DNA was clean and digital. It reminded engineers and IT people of computer code, and the analogy still used was born that DNA was indeed the computer code of life.

    Most biologists were less giddy about DNA. From the start, they suspected that the biology of humans at the molecular level would be more complex, and that the idea that a "gene" for common diseases like diabetes and heart disease could be identified and a drug made to modulate this "target" was too simplistic. And yet this model became a primary thrust of most pharma companies — and for many, it still is.

The biologists were right

    For most of us, our DNA is part of a complex dynamic that includes the impact of the environment — food, UV rays from the sun, toxins — and the interplay of everything from microbes that dwell inside our bodies to a host of structures in our cells that interact with and impact DNA.