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PBS: Flood of new drugs from human genome map “unmitigated failure”

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Because the genome is only a parts list. But there’s hope.

From PBS:

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.

Epigenetics?

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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Comments
OT: Darwinians Try to Usurp Biomimetics Popularity - October 9, 2014 Excerpt: "it is remarkable, therefore, that formal mathematical, rather than verbal, proof of the fact that natural selection has an optimizing tendency was still lacking after a century and a half later.",,, More importantly, its proponents are still struggling, a century and a half after Darwin, to provide evidence and the mathematical formalism to demonstrate that random natural processes have the creative power that Darwin, Dawkins, and others claim it has. Everyone already knows that intelligent causes have such creative power. http://www.evolutionnews.org/2014/10/darwinians_try090231.htmlbornagain77
October 11, 2014
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A couple of months ago News quoted this practical suggestion by William P. Hanage in Nature:
Press officers must stop exaggerating results, and journalists must stop swallowing them whole.
then added:
Science writers should lose the pom poms.
:) And now this funny observation:
“Omes” are listed more often these days in biology than in a new subdivision.
:)Dionisio
October 11, 2014
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2 DavidD Interesting point. Thanks. Now, on the side: Can morality be legislated? What should be the best motivation for doing scientific research? Improving public health or knowing nature better? Something else? All of that? None of that?Dionisio
October 11, 2014
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Nice find News! :) Well worth the read.,,, especially nice to find out that even antibiotic resistance refuses to be explained by a 'bottom up' neo-Darwinian process!
The Diseaseome Could Take Medicine Beyond the Genome By Cynthia Graber on Thu, 09 Oct 2014 Excerpt: 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. With this new understanding, Collins and his lab set out to combat antibiotic resistance. Collins’ lab introduced an extra protein to antibiotics that flips on DNA repair activity within the cells. Repairing the DNA prevents the mutations that create antibiotic-resistance in the first place. In studies, this process boosted the efficacy of a drug such as Cipro from ten times to a thousand fold. Collins has since founded a company, EnBiotix, to attempt to commercialize this approach and improve the efficacy of existing antibiotics. He expects that the newly improved antibiotics—based on a network approach—could be tested in clinical trials within the next couple of years. http://www.pbs.org/wgbh/nova/next/body/network-medicine/
bornagain77
October 11, 2014
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A large part of ridding human beings of disease and other ailments is to curb irresponsible behavior that brings such consequences about. The fact is most humans like 'sin', they simply don't like it's consequences and demand that science do something about it. Alcoholics want their over indulgence in booze, smokers love smoking, but don't want lung cancer or emphysema, young people want recreational sex , but don't want unwanted pregnancies or disease. Homosexuals want gay sex, but not AIDS, Syphilis, etc. The list is endless, but stopping the bad behavior and wrong choices in life is never an option on the table. Science will eventually fix it, or so the religious chant insists. More than anything else, these are the reasons behind some of these stupid arguments and debates on many of these forums. These people resent definitions of morality and submission to higher authority, it never was about science in the first place. Science is a crutch and excuse for all the lame at heart and mind.DavidD
October 11, 2014
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Sometimes it seems like one important thing pseudoscience lacks is the bottom line simplicity of childlike questioning: how? why? what for? where from? etc. Completely detached from biased presuppositions. The state of affairs is really pathetic these days. :(Dionisio
October 11, 2014
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