As Business Races to Decipher Proteins,
Is Equal Effort by Government Desirable?
By DAVID P. HAMILTON and ANTONIO REGALADO
Staff Reporters of THE WALL STREET JOURNAL
The race to map the human genome had government-funded researchers vying with private companies to reach the same goal. Now a new marathon -- deciphering the body's entire collection of proteins, known collectively as the "proteome" -- is under way, and a question that dogged the genome project is being raised again: Is a government-funded effort necessary when so many biotech companies are already involved?
At a protein-research meeting in McLean, Va., this week, many scientists argued that a large public effort is necessary to coordinate a variety of otherwise independent efforts and to ensure that protein data are widely shared. But some in industry demur, noting that existing commercial efforts may render a public project redundant. "It's not like when the genome project started, when no one thought about large-scale projects -- now everyone does," says Jim Garrels, a vice president at Incyte Genomics, Palo Alto, Calif. "Proteomics is already happening."
Indeed, since a better understanding of proteins can lead directly to new drugs and other therapies, the quest for a map of the proteome has become a big business, involving millions in venture capital and Wall Street investment and scores of corporate efforts.
Among those in the new race is Myriad Genetics Inc. of Salt Lake City, Utah, which Wednesday announced a major project to comprehensively map out the ways human proteins interact with one another in just 1,000 days. In conjunction with three partners who will supply computer hardware, software and $85 million in cash for the project, Myriad intends to build a proprietary database of those interactions, and eventually a catalog of all human proteins as well, that it can market to other biotechnology and pharmaceutical companies for use in drug development.
"The key to using this information successfully lies in understanding protein function, and the pathways proteins form can be linked to human disease," says Myriad's chief executive officer, Peter Meldrum. "No one else has announced anything as ambitious as mapping the human proteome." Myriad shares, however, dropped 9.5% on the announcement, changing hands at $30.77, down $3.23, in 4 p.m. trading on the Nasdaq Stock Market Wednesday.
The emerging field of proteomics is a natural successor to the human-genome project, in which scientists mapped out the roughly 30,000 genes that store genetic information in the human body. Genes, however, are little more than sets of instructions for building proteins, the true molecular workhorses of the body. So to figure out how the inner machinery of cells works, how malfunctions can lead to disease and how to make new drugs and diagnostic tests, scientists need a much more comprehensive understanding of proteins.
While conceptually simple -- all proteins are essentially lengthy chains with links made of 20 different amino acids -- protein functions and their three-dimensional structure are mind-numbingly complex. No one knows how many proteins exist in the human body, although tentative estimates run from about 300,000 to as many as three million.
Worse yet, proteins in the body are often muddled together in a thick soup, complicating the process of isolating them and determining their functions. Those actions can range from giving organic tissues their structure to fighting disease.
Myriad may have an aggressive timetable, but it is far from alone in wanting to stake a claim to the proteome (pronounced PRO-tee-ohm). AxCell Biosciences, a unit of Cytogen Corp. of Princeton, N.J., plans in just two to four years to finish up a comprehensive description of the way protein subunits called domains stick to one another. Such stickiness, or "binding," lies at the heart of most protein functions.
Integrative Proteomics Inc. of Toronto plans to go a step further by building a catalog of proteins and submitting them to X-ray and magnetic-resonance analysis that can determine their three-dimensional structure. Such information can be crucial to the development of new drugs, whose function often depends on the ability of drug molecules to wedge themselves into nooks and crannies of disease-related proteins. So far, IPI has focused on the proteins of disease-causing bacteria, although it plans to move on to human proteins next year.
Still, not all biotech companies believe in a comprehensive effort to categorize human proteins -- especially not J. Craig Venter, the contentious head of Celera Genomics Group, a Rockville, Md., unit of holding company Applera Corp., and a longstanding critic of the public genome-sequencing effort.
"There ain't no such thing as a proteome," Dr. Venter declares. Human proteins vary so widely from cell to cell that a comprehensive catalog would be practically impossible to achieve and of dubious utility, he says. Instead of cataloging all proteins, Celera plans to focus on unearthing new proteins associated with particular diseases and using them to develop vaccines, tests and other therapeutics.
Many academic scientists argue that such efforts, while laudable, illustrate the need for a single body that could help coordinate research efforts and advance human knowledge as a whole, not just corporate agendas. Unlike the genome project, where DNA sequencing technology propelled the project towards a single easily understood goal, the proteomics field is driven by an array of emerging technologies and has multiple goals. Scientists would ultimately like to identify all human proteins, determine the shapes they assume inside cells and understand their function by observing how they change in different circumstances.
In February, academics and companies formed a group known as the Human Proteome Organization to try to provide some help coordinating protein research. Today's private-sector efforts won't be comprehensive; Myriad's effort, for instance, won't reveal structural information and will leave many questions about protein function unanswered.
Similarly, scientists worry that protein data produced by companies will remain locked up in proprietary databases, where they will benefit only companies willing to pay for the information. Myriad's Mr. Meldrum says the company plans to charge even academic researchers for access to its data, although it plans to do so in a "cost-effective" way.
"We have to step up and try and coordinate this because all the data should be made freely available," says Trevor Hawkins, director of the Department of Energy's Joint Genome Institute. "We aren't in a position to say that some things should be available and others not."
And Now the Proteome
A sample of companies planning large-scale projects to study proteins
COMPANIES PROJECTS
Celera Genomics, CuraGen, Incyte Genomics, Myriad Genetics Traditional players in the gene business are rushing into proteomics, hoping to ink more research alliances
Large Scale Biology, Oxford Glycosciences Reading out the levels of thousands of proteins at once from diseased tissues could lead to new markers to detect cancer and other problems
Applied Biosystems, MDS Proteomics, MicroMass New 'mass-spectrometry' machines being developed by these companies could be the workhorses of the proteomics era
GeneProt, Glaucus Proteomics, Hybrigenics These spin-outs from European universities reflect the region's traditional strength in protein biochemistry
Hitachi, IBM, Motorola Large software, computer and electronics makers are trying to develop new 'life sciences' markets for their products
Ciphergen, Illumina, Zyomyx Private start-up companies are chasing a breakthrough in protein 'chips,' a miniaturized technology for making biological discoveries
Integrative Proteomics, Structural GenomiX, Syrrx These start-up firms are racing to crack the 3-D structure of proteins; a separate effort by the National Institutes of Health has similar aims
Source: WSJ research |
