Thanks to All the Little Genomes

Opinion: Bioinformatics can help develop vaccines and otherwise fight disease by helping to interpret the sequencing of human pathogens.

Yes, the Human Genome Project is impressive, but our self-centered fixation is causing us to overlook genetic work that could be just as important—and yield rewards far sooner.

The top 50 human pathogens have all been sequenced. Malaria, tuberculosis, typhus and your ilk, weve got your number. Actually, better yet, weve got your genomes.

Those who think this is only good news for the developing world should remember that the research community was shocked to learn bacteria cause stomach ulcers, and that infections are suspected in heart disease, atherosclerosis, cancer and even some psychoses.

But its not the genomes themselves that will spark ideas for fighting disease. Nowadays, applications of genomics owe more to computational tools (bioinformatics) than to the sequencing machines that actually read out the As, Gs, Ts and Cs.

Even the head of one of the worlds leading sequencers says so. "Bioinformatics is an enabling technology," said Claire Fraser, president of TIGR (The Institute for Genomic Research); "DNA sequencing would be of little value without it."

/zimages/7/28571.gifRead more here about the developing standards for bioinformatics.

Bioinformatics turns a string of letters into useful information. Though the technology isnt perfect, it means computers can hunt through gene sequences and make broad guesses as to what they do.

Does the protein made from the gene stay inside the cell to keep its innards running smoothly? Is it, like insulin or growth hormone, pumped out of the cell to trigger action elsewhere? Or perhaps the protein lodges in the cell membrane to detect whats happening outside and tell the cell how to adapt?

With sequences of related bacteria, bioinformaticians can figure out what genes make one bacteria harmless and another dangerous. Or what makes one bacteria unable to infect humans while its cousin wreaks havoc in our organs.

As powerful as antibiotics are, our armory is limited, and shrinking with antibiotic resistance. The thirty or so marketed antibiotics fall into just three classes, Fraser told attendees at a scientific conference last month. They either disrupt cell walls, muck up DNA replication and repair, or keep a pathogen from making the proteins it needs. But sorting through the genomes reveals all sorts of other ways to attack infectious disease.

To some of you, the last sentence sounds awfully familiar. In the 1990s, biotech stocks skyrocketed in anticipation of the medical windfall from the human genome sequence. That has been slow in coming, but their counterparts are arriving for infectious disease, which have less than a tenth the number of genes we do.

/zimages/7/28571.gifA leading medical journal called for genomic data on pathogens to remain widely available, saying the benefits of promoting medical research far outweigh the risks of helping bioterrorists. Click here to read more.

Researchers can find the genes that code for how a pathogen interacts with human cells, or look for drugs that can knock off problematic bacteria without attacking the helpful ones in your gut.

But the most promising developments may be the technologies use for designing vaccines in silico.

First, bacterial genes are analyzed by a computer to find ones that make proteins that are located where the human immune system can detect them, like those on the bacterias cell wall. Next, lab experiments determine which are likely to prompt an appropriate immune response.

Using this approach, researchers working together at Chiron and TIGR discovered five new experimental vaccines for meningitis. These moved from idea to human trials in just two years, a pretty speedy pace for vaccine development.

With the sequences in hand, such an approach to vaccine-making can become routine, predicted Fraser.

Next Page: Non-viral pathogens that infect humans.