Because the genome is only a parts list. But there’s hope.
When scientists first published the initial results of the human genome in 2001, we seemed to be on the precipice of a revolution in medicine. Researchers could finally discover specific genetic mutations that lead to diseases. Pharmaceutical companies could devise scores of new drugs to target those mutations. Patients could be treated based on their individual genetic patterns.
So far, though, some scientists say the results have been disappointing.
But the flood of new drugs based on the genome hasn’t arrived. “It’s been an unmitigated failure from my perspective,” says Joseph Loscalzo, head of the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, referring to so-called genome-wide analysis studies that mine genetic data in the search for new targets for drugs.
Loscalzo admits that the scientists involved may disagree with his forceful statement, but he points out that very few diseases have been linked to only one or a small number of genes. Even ones that are classically tied to a person’s genetics, such as sickle cell anemia, can cause vastly different symptoms, due, says Loscalzo, to the “genetic context” in which the mutated gene operates. For more complex and prevalent diseases, like cardiovascular disease—Loscalzo’s specialty—few patients have the same genetic variation or even the same symptoms.
A new concept is the diseasome:
Barabási likens the diseasome to a map of Manhattan: there are certain clusters where various activities take place—theater along Broadway, finance on Wall Street, advertising agencies on Fifth Avenue. The same is true for the patterns in a cell, though it doesn’t necessarily happen in physical space, the way neighborhoods cluster in a city. Rather, they play out in the chemical networks within a cell—specifically, which proteins, genes, and other chemicals are connected to one another. Using powerful computers to map these networks, researchers have been able to find regions where the connections that make up a particular disease “clump” together. They call these the “disease modules” in the network.
Scientists have been able to find some of these modules. In a presentation at Dana-Farber Cancer Institute, Barabási described how the team of researchers had analyzed 300 diseases. They tried to determine whether the genes that are known to have a connection to a particular disease link up to each other through gene and protein interactions.
They found that 20% of disease-related genes form a connected network in a disease module. The other 80% are in the vicinity; they connect to the diseased genes through one non-diseased gene.
By the way, remember the Darwinian explanation for antibiotic resistance in bacteria? This is an alternative explanation:
Today, antibiotic resistance is thought to emerge because, scientists have believed, there are a few bacteria in a given community that are naturally resistant to a drug, and they thrive after the drug kills off the bacteria’s brethren. But instead, as Collins’ research has demonstrated, antibiotics themselves induce mutations, leading to antibiotic-resistant bacteria. More.
One caution, and maybe it is merely a linguistic one: “Omes” are listed more often these days in biology than in a new subdivision. See, for example, Harvard epidemiologist William P. Hanage offers five skeptical questions about the microbiome.
The underlying concepts sound promising; we’ll see whether the lable “diseasome” survivesl
See also: Interactome? Well, remember genome, proteome, old folks home …
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