Rare Mutation Kills Off Gene Responsible For Diabetes | Hacker News Reader

Rare Mutation Kills Off Gene Responsible For Diabetes

nytimes.com

67 pointsmhb23 comments

What's very interesting about this discovery, perhaps even more so than the discovery about Diabetes, is that the results directly contradict research that was conducted on Mice.

So much medical research, and drug trials, are based on the what the reactions of mice are; this discovery makes it clear we cannot rely on mice for everything.

If you read to the end of the article (spoiler) - the original paper was rejected for publication because it contradicted research that showed what was happening in humans, could not be occurring because mice reacted differently.

I've been saying this for years. Most of the tox studies or efficacy studies in mice have poor or no models that correlate with human biology. They are indicative at best but should never be used to give a black or white story. The pharma industry and academia is throwing every single year dozens of potentially active molecules because they see toxicity in animals. Note that animals models have also permeated the regulatory bodies, therefore making it into de facto requirements to develop drugs. And it is so rarely ever contested on scientific grounds, where the Science part is effectively very thin.

So, we need a better mouse.

How are computer simulation at modelling drug efficiency? Better than mouse, worse, unknown?

I think they are poor because there are so manny factors involved that it's difficult to create a reliable model. But I don't know, so this is my opinion. Computers could probably help test simple hypotheses but I don't think they could be used as evidence to begin human trials.

>deCODE Genetics, a company with data on genes and diseases for the entire population of Iceland. The American drug company, Amgen, bought deCODE and its valuable genetic database.

Based on Iceland's reaction to its financial crisis in 2008, I would not have expected such a dataset to be privately held.

It seems in 1998 the Icelandic Parliament "permitted public bidding for the right of a company to create" a "population-wide genomic biobank by collecting data from the entire population of Iceland". It then granted deCODE "the right to create this database after the company made a successful bid to do so" [1].

[1] http://en.wikipedia.org/wiki/DeCODE_genetics#History

Wasnt expecting this either. And now the whole database is owned by multi-national pharmaceutical.

There was a lot of discussion about the whole thing when the bid was made by deCODE. When they got the permission, people were allowed to opt out, but the general attitude towards the company was far too positive at the time.

I got excited reading the title thinking it was Type 1. Sigh, more waiting I guess.

"...even fat people.."

"..the fat old people..."

Is that proper language for an NYT article? It reads more like something from The Onion.

I found the gratuitous use of the word 'fat' in this article kind of jarring.

It only appears three times, is a proper medical term, and is absolutely relevant to the article subject.

"Fat" as a description of a person is as medically valid as "stupid". That is to say, not at all. "Overweight", "obese", and others are actual medical terms that have real definitions, quite unlike "fat".

Agreed. All instances of the word "fat" are used by the writer. The only instance of a medical professional saying something that would warrant the word "fat" is Dr. Rolph, who is quoted as saying "overweight."

Oh, I see. So synonyms of the word "fat" have real medical definitions. I think it's just that "fat" doesn't sound pretentious enough, so it's not clinical.

They don't mean precisely the same thing. "Overweight" and "obese" can be defined, as categories, according to BMI, WHR, body fat percentage or similar. "Fat" is a lot less clearly definable.

I guess someone should notify Merriam-Webster: http://www.merriam-webster.com/medlineplus/fat

Maybe it's like "retarded"? It was jarring to see in medical texts, but they use it.

Yup, the proper term is gravitationally challenged. Now can we stop this PC bovine excrements thing?

There must be some law where it takes at least 10 years before a medical discovery becomes a treatment available to the general public.

There's no Moore's Law or exponential growth in medical research. We'll probably all dying from the same diseases in 30 years as we're dying from today, with some small improvement.

Once we figure out gene therapy there'll be a Moore's law. Until then, we're stuck with the inverse Moore's law of small molecule drug design.

http://rogerpielkejr.blogspot.com/2011/02/innovation-in-drug...

That's because "destroy a gene" is not a treatment. The process of finding a molecule that inhibits the action of the gene, is not rapidly metabolized by the body, is capable of crossing the cell membrane, and doesn't kill people at the same dose as it has its effect takes a while. You have to try a lot of molecules to find one that satisfies all these requirements. There are efforts to speed up the early selection process, such as using computational chemistry approaches to compute which molecules can "dock" with a protein's active site. This is hard though, because proteins & small molecules are not rigid, so it's much harder than just doing a jigsaw puzzle in 3-D. I'm sure robotics is also being used to speed up the initial drug screening, but I know less about that.

Also consider that there's no way to tell the long-term toxicity of a drug except by running a long-term study.

Basically, my dad (who works as a pharma researcher) told me almost exactly what you proposed: it takes 10-20 years to develop a drug and bring it to market once you have a target to develop against.

> I'm sure robotics is also being used to speed up the initial drug screening, but I know less about that.

Yes, for combinatorial screening. But these are very simple robots.

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