On June 26, 2000, President Bill Clinton and Prime Minister Tony Blair jointly announced that researchers had completed the first draft of the human genome, a map that spelled out the three billion letters of the genetic code. “Without a doubt, this is the most important, most wondrous map ever produced by humankind,” said Clinton. Blair was equally effusive. “Let us be in no doubt about what we are witnessing today-a revolution in medical science whose implications far surpass even the discovery of antibiotics, the first great technological triumph of the 21st century,” said Blair.But neither leader uttered a word that would soon take over the allure and promise that “genome” once enjoyed everywhere from the White House to Wall Street: “proteome.”
Just as genomics is the attempt to decipher all of the genes in an organism, proteomics, in its simplest definition, aims to uncover all of the proteins and their functions. Since genes are simply the blueprints for proteins, which in turn are the main players in most of the body’s functions, it’s a logical progression. Indeed, there is no mistaking what proteomics promises: a revolution in medical science with implications that far surpass those of genomics.
Sounding an awful lot like the genomics gurus of yesteryear, proponents of proteomics declare that a “global understanding” of proteins will reveal the underlying mechanisms of disease, leading drugmakers to treatments that ablate causes rather than mask symptoms. Companies will discover a bounty of natural proteins that can serve as injectable drugs, the advocates assure, as well as an abundance of new protein targets for the “small-molecule” pills that are the cornerstone of the pharmaceutical industry. Side effects will plummet as the precision of treatments increases. A finer appreciation of the differences between the proteomes of individuals will allow doctors to tailor treatments to specific populations. And as new technologies emerge-your entire proteome on a chip?-medicine will advance in ways that even the most farsighted visionaries cannot imagine.
All of which has helped proteomics replace genomics as biology’s new new thing. “Genomics is dead,” declares N. Leigh Anderson, who heads Large Scale Biology’s proteomics subsidiary in Germantown, MD.
Anderson and other proteomics enthusiasts argue genomics provides only rough clues about the workings of the body. And they question the many scientists who tightly tied the deciphering of the human genome to drug discovery. “To some extent, they’ve sold the public a bill of goods in genomics,” says Anderson. Scott Patterson, who leads the proteomics project at Rockville, MD-based Celera Genomics, similarly sees serious shortcomings in some of the most celebrated drug-hunting strategies used by genomics companies-like studying arrays of genes without considering that the body modifies the proteins they code for in myriad ways. “Maybe everyone forgot their microbiology,” says Patterson, whose company infamously raced (and goaded) the publicly funded Human Genome Project.
Investors, it appears, have not. Since June 26, 2000, more than $700 million has poured into proteomics companies from venture capitalists and IPOs. In addition to the swarm of startups that focus on proteomics, many genomics companies now have proteomics branches, and most every big pharmaceutical company has a proteomics-oriented biotech partner or has started its own proteomics division. And because proteomics makes heavy demands on computing power, deep-pocketed cyberstalwarts like IBM, Hitachi, Oracle, Compaq Computer and Sun Microsystems have joined in, too.
Still, not everyone shares the excitement. Some leading scientists worry that yet another bill of goods is being writ before their eyes. Sydney Brenner, who helped launch the Human Genome Project, says the proteomics craze is not about new knowledge but about amassing data-most of which he predicts will have no impact on drug discovery. “I think there will be a backlash,” says Brenner, now at the Salk Institute for Biological Studies in La Jolla, CA. “I really think people will come to their senses. Science will just walk around them. [Proteomics] will prove to be irrelevant.”
Even some proteomics leaders grimace at its popularity. “Today, many people try to use the word proteomics,’ and I wish people did not like it so much,” says Denis Hochstrasser, who does proteomics research at the University of Geneva in Switzerland and chairs the scientific advisory board for Evanston, IL-based startup GeneProt. “People expect too much from a buzzword, and they don’t realize what’s behind it.”
For all its promise, proteomics remains strapped by serious limitations. The technologies to isolate and characterize proteins are still cumbersome and insensitive. Add to that the sheer vastness of the human proteome, and deciphering it presents an arrestingly complex mission. And while some academic and industry researchers have launched targeted efforts to tackle small bits of the puzzle, none resemble the organized effort to decode the human genome. “It’s difficult to conceive of the idea of a human proteome project,” says Celera’s Patterson. “I just don’t know when you’d ever say you finished. It’s bad enough trying to figure out if you’ve finished the human genome project.”
Yet the completion of the human genome does give proteomics an unambiguous starting point. Many new technologies have sprouted in the past few years that make it easier to find and identify proteins. And the detailed description of the human genome provides researchers working in proteomics a powerful new tool to chart, at least in a broad sense, the many technological and organizational challenges that lie ahead.