The Year of Miracles

The rest of the biomedical community refused to believe that robots could analyze something as complex as a living system. And in any case, no practicing geneticist had the capacity to design such machines. Unable to obtain government grants, Hood secured private funding to bring together dozens of scientists, engineers and computer programmers (far larger and more diverse than any other genetics team). They proceeded to invent the first generation of molecular-biology machines. Two read and recorded information from DNA and proteins respectively (a process known as sequencing), and two others worked backward, converting digital electronic information into newly written sequences of DNA or protein.

Hood completely transformed the biomedical enterprise. DNA-writing machines give genetic engineers an unlimited capacity to create novel genes that can be studied in test tubes or added to the genomes of living organisms. And protein-writing and -reading machines provided drug firms with the ability to create a new generation of protein-based drugs. The DNA-reading machines suddenly made it conceivable to crack the 3 billion-base sequence of an entire human genome. In 1990 the U.S. government embarked on a 15-year, $3 billion project to do just that.

Eight years later, however, the project—parceled out to many U.S. scientists—was still less than 10 percent complete. Now it was biotech entrepreneur Craig Venter who was frustrated. Convinced that government-funded workers were the problem rather than the solution, Venter enlisted private funding of $200 million to build an enormous lab filled with hundreds of automated machines, working 24/7, overseen by a handful of technicians. Within three years, the first reading of a human genome was essentially complete.

Armed with data from the genome project, scientists figured they'd surely be able to crack the really hard diseases, like cancer and heart disease. But a funny thing happened when they began to look closely at this vast storehouse of genetic information. Geneticists Andrew Fire and Craig Melo galvanized the field by discovering a key mechanism that had been completely overlooked—the cellular process of RNA interference. (They shared a Nobel Prize in 2006 for the work.)

Finding evidence of extraterrestrial life couldn't have come as a bigger shock. Geneticists had taken for granted that the machinery of cells involved genes directing the production of proteins, and proteins doing the work of the cell. Here was a process that didn't involve proteins at all. Instead, tens of thousands of hitherto mysterious regions of the human genome—part of the so-called junk DNA—directed the production of specific molecules called microRNAs (consisting of bits of RNA, a well-known component of cells). These microRNAs then oversaw a whole new process, called RNA interference (RNAi), that served to modulate the expression of DNA.

The good news was that RNAi could open up a whole new approach to biomedical therapy (more on that later). But RNAi also made it clear that the fundamental unit of heredity and genetic function is not the gene but the position of each individual DNA letter.