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"Their drugs still keep people alive regardless of the motivation for their creation."

But not at any price.

And it continues...

http://pipeline.corante.com/ar...

make sure nobody got hurt and don't start a fire you can't put out.

"Sand won't save you this time". Obligatory any time someone mentions not stating fires in the context of chemistry experiments.

For those who need a taster,

if there was anything that would go on to set the [wet] sand on fire.

Eh? set and on fire?

Let's put it this way: during World War II, the Germans were very interested in using [the compound of interest] in self-igniting flamethrowers, but found it too nasty to work with.

That's a good start, considering that the Germans in WW2 used some pretty ... vigorous ... chemistry.

a practical consequence of that is that itâ(TM)ll start roaring reactions with things like bricks and asbestos tile

More "Eh?"

It burned its way through a foot of concrete floor and chewed up another meter of sand and gravel beneath, completing a day that I'm sure no one involved ever forgot. That process, I should add, would necessarily have been accompanied by copious amounts of horribly toxic and corrosive by-products:

By now, anyone who is worried about the chlorine in water sterilisation should be running away, and anyone with a solid footing in chemistry will be donning the leather aprons and steel blast-shields and edging cautiously to the front of the lab. Fun stuff!

Derek Lowe, In The Pipeline, I got into him from his Things I Won't Work With tag (Note: he's going to be moving to another domain in a few weeks)

Stephen Smith's Space KSC (I think he's a bigwig with NASA's outreach or advocacy programs or something)

Bunnie Huang's blog (famous for hacking the Xbox, but he isn't updating very often this year, so he must be working on something)

Derek Lowe, In The Pipeline, I got into him from his Things I Won't Work With tag (Note: he's going to be moving to another domain in a few weeks)

Stephen Smith's Space KSC (I think he's a bigwig with NASA's outreach or advocacy programs or something)

Bunnie Huang's blog (famous for hacking the Xbox, but he isn't updating very often this year, so he must be working on something)

I like to read Derek Lowe's blog "In the pipeline". It has good insights on the pharma industry, drug development, etc. If you go there be sure to check the "Things I won't work with" page. It makes for some very entertaining reading on "exciting" (as in "oh my god we all gonna die") chemical substances.

I like to read Derek Lowe's blog "In the pipeline". It has good insights on the pharma industry, drug development, etc. If you go there be sure to check the "Things I won't work with" page. It makes for some very entertaining reading on "exciting" (as in "oh my god we all gonna die") chemical substances.

The original paper for this was discussed yesterday on In The Pipeline. The point was raised that the mechanism involved, the JAK-STAT signalling pathway is used quite broadly throughout the body in the control of cell growth and differentiation. There are several Janus Kinase (that's JAK) inhibitors already on the market or in development, and they are powerful immunosuppressants indicated for the treatment of things like rheumatoid arthritis or leukemia. They tend to be the sorts of drugs whose advertisements say stuff like, "Xeljanz may increase your risk of serious infection." Notably, Xeljanz (tofacitinib) popped up in the news a few months ago when it was used to grow hair in a patient with alopecia universalis (who was already taking the drug for an autoimmune disease) and the headlines exclaimed that a cure for baldness was on the horizon. Now, a single drug that burns fat, grows hair, and relieves psorasis sounds like a miracle, but the reality is that's a sign that these compounds act more broadly than is desirable.

As the paper's authors themselves put it:

The utility of JAK inhibition as a therapeutic strategy for obesity is complicated by the well-described role of this signalling pathway in the immune system. In fact, tofacitinib is approved in the United States to treat rheumatoid arthritis. Thus, if one were to imagine targeting adipose tissue by in vivo administration of an IFN–JAK–STAT inhibitor or similar compound it would almost certainly need to be delivered locally and prevented from spreading systemically or alternatively targeted selectively to white adipocytes. One could also conceive of a cell-based therapy wherein JAK inhibition of patient-derived adipocytes ex vivo is followed by transplantation to treat obesity, but this therapeutic modality would need to overcome numerous and significant obstacles before becoming a reality.

Also, it's odd: Nobel prizes used to be given to things which hae proven their worth. Super-res microscopy while cool and wile showing a *lot* of promise has not yet reached the stage where it looks more than "very very promising".

Eh, I'm not so sure about that. Sometimes the prize is for research done decades ago that turned out to be really fundamental, and sometimes it's for huge breakthroughs that fundamentally and immediately change what we're capable of doing. This certainly looks like the latter to me.

That figure is misleading in the extreme. Even the 1 billion figure is low-balling it.

That figure is misleading in the extreme. Even the 1 billion figure is low-balling it.

That figure is misleading in the extreme. Even the 1 billion figure is low-balling it.

I wish that were true. It sure looks like the US funds a vast majority of drug marketing, though.

But for completeness sake, here's some counterpoints.

I wish that were true. It sure looks like the US funds a vast majority of drug marketing, though.

But for completeness sake, here's some counterpoints.

It's also shit like taking colchicine, which has been cheap and generic for years, doing a little extra research (which arguably was useful) and then using that status to bump the price up by 15 times.

Those people taking the drug couldn't give a shit about the research - they take the pills, their gout gets better, that's their own personal research right there. What sticks in their craw is that their pills now cost $5 apiece.

That and the systematic hiding of research that is negative or equivocal, the deliberate creation of medicines that are just a couple of atoms different from an existing one, not because they'll be better but because they'll be on patent, etc, etc.

Big pharma does a lot of good, but it's kind of like picking gold coins out of a midden.

Bugger. Wrong HTML element. Things I won't work with.

Not only with oxygen. Chlorine and fluorine oxidize stuff way faster. That is why ClF3 is so much "fun".
(burns sand, burns concrete, burns water, burns glass, burns workbenches, burns researchers, burns labs, burns buildings. All while emitting nasty fluorine based gasses like large quantities of HF. Fun stuff.)

This article covers a bit of the complexities involved:

http://pipeline.corante.com/ar...

"a) students are quite gungho when it comes to their work and will quickly take shortcuts because they don't know any better or don't have the right tools, example: I didn't see a wire stripper till I got to industry, I used to do it by pressing the wire to a knife using my thumb and I got many cuts as a result."

Students being the only gung-ho ones? Bwahahahahaha.... Students being gung-ho is a result of PI's and others not having a proper safety mindset, or even deliberately pushing students to ignore safety, or not teaching it at all...

http://pipeline.corante.com/ar...

"Recently we found ourselves with an odour problem beyond our worst expectations. During early experiments, a stopper jumped from a bottle of residues, and, although replaced at once, resulted in an immediate complaint of nausea and sickness from colleagues working in a building two hundred yards away. Two of our chemists who had done no more than investigate the cracking of minute amounts of trithioacetone found themselves the object of hostile stares in a restaurant and suffered the humiliation of having a waitress spray the area around them with a deodorant."

http://pipeline.corante.com/archives/2009/06/11/things_i_wont_work_with_thioacetone.php

I am not a shill for the drug companies by any means. That being said, I think the third world's energies would be better spent dealing with their quality issues before they got butt hurt over this move by big pharma's lobby. In reality, drugs sourced from India and/or China are a crap shoot. Read Derek Lowe's blog "In the Pipeline" for information on this industry and pharmacological chemistry.

Yes, India may be getting unfairly punished for it's ability to manufacture drugs inexpensively, but unfair things go on all the time - just look at Slashdot beta!

it doesn't keep burning through the earth's crust all the way to China

This is clearly a design flaw. I suggest chlorine trifluoride.

If you enjoyed that, you might like the "Things I Won't Work With" posts on Derek Lowe's blog since he writes with a similar style.

Numbers? Yes. Quality? No. Look at the recent scandals about selling co-authorship of pre-written scientific papers to boost one's publication count. Many horror stories about scientific publishing in China can be found here.

Sand itself burns as well, becoming mostly ash in a complex chemical reaction.

... and you're obviously confusing burning the oil that is in the pore spaces between the sand grains. Don't worry, it's a common confusion. I deal with it on a weekly basis because I'm an oil geologist by trade.

But when I'm talking about "burning sand", I'm talking about chemicals that you can pour onto some sand - clean sand, that you could melt to make clear window glass - which will burn it, make it red hot, and produce clouds of less energetic chemicals which will dissolve the skin, lungs, bodies and bones of someone unlucky enough to be nearby.

In a comment to my post on putting out fires last week, one commenter mentioned the utility of the good old sand bucket, and wondered if there was anything that would go on to set the sand on fire. Thanks to a note from reader Robert L., I can report that there is indeed such a reagent: chlorine trifluoride.

If you have the remains of school chemistry hiding in the back of your memory, I heartily recommend the page. It will bring tears of ... something .. to your eyes. Which isn't good if there's phosphorous pentoxide dust in the air, as the resulting acid will eat your eyeballs. Painfully.

itâ(TM)ll start roaring reactions with things like bricks and asbestos tile

Joy!

So much ignorance here! Here's a working scientist's opinion:

http://pipeline.corante.com/archives/2013/10/16/holding_back_experimental_details_with_reason.php

And Derek Lowe is about as libertarian as scientists get.

The problem is that the game is never actually released to the public. Because the code is never made available, except in a few rare cases. So the 'contract' with the public that gave them copyright is now violated because we don't get ever get the content into the public domain.

I disagree. I think it's reasonable to view proprietary software's source-code as nothing more than an internal development aid used by the software-house, even though certainly there would be advantages to eventually making source-code public-domain.

How about games that require activation servers? How in the hell will you get to play the game in 75 years when said servers are long since dead?

There needs to be a repository where software code gets placed so that when it's copyright is expired it gets released to the public. Or something like that so we actually get the creators to honor their end of the deal.

Viewing video-games (and indeed DRM'ed software in general) as art, or at least of historical interest, this is indeed worrisome, but I don't agree that software producers should be forced to hand over their source-code to the government. For one, it breaks the elegant simplicity that you don't have to do anything special to have the copyrights to your work. Also, I'd never trust a government database of source-code not to be hacked, releasing (legally unprotected) trade-secrets prematurely.

Regarding software patents, I share your view (the prevailing view on Slashdot) that they're probably generally a Bad Thing. Here is the best counter-argument I know of. (In short, that one can't forbid software patents without forbidding hardware patents. How New Zealand deals with the issue, I'm not sure.)

Lets not even talk about synthesising Ammonia, hydrofluoric acid, or methyl isocyanate. The entire process industry seems intent on trying to do the craziest shit possible.

If you think synthesizing those is fun, just take a look at the Things I Won't Work With. Mentions of things like Dioxygen Difluoride and Chlorine Triflouride. Apparently Xenon difluoride is a stable compound.

Lets not even talk about synthesising Ammonia, hydrofluoric acid, or methyl isocyanate. The entire process industry seems intent on trying to do the craziest shit possible.

If you think synthesizing those is fun, just take a look at the Things I Won't Work With. Mentions of things like Dioxygen Difluoride and Chlorine Triflouride. Apparently Xenon difluoride is a stable compound.

Lets not even talk about synthesising Ammonia, hydrofluoric acid, or methyl isocyanate. The entire process industry seems intent on trying to do the craziest shit possible.

If you think synthesizing those is fun, just take a look at the Things I Won't Work With. Mentions of things like Dioxygen Difluoride and Chlorine Triflouride. Apparently Xenon difluoride is a stable compound.

Well, they won't literally burn (or rather decompose) "on their own" at room temperature, but John Clark's excellent rocket-science book "Ignition!" describes ClF3 thus:

It is, of course, extremely toxic, but that's the least of the problem. It is hypergolic with every known fuel, and so rapidly hypergolic that no ignition delay has ever been measured. It is also hypergolic with such things as cloth, wood, and test engineers, not to mention asbestos, sand, and water-with which it reacts explosively.

More about these oxidizers and many other exciting chemical curiosities may be found in Derek Lowe's Things I Won't Work With series.

Yes, that's a known problem in chemistry. So there's a growing movement to require an independent lab to replicate results before publishing - Reproducibility Initiative. See: http://pipeline.corante.com/archives/2012/08/14/reproducing_scientific_results_on_purpose.php

If you want it gone, spray it with FOOF

[source needed]

Sorry, a couple of years ago I looked at a year's worth of drug approvals and came up with 15%. The actual data (1998-2007) say 24% came from academia:

http://www.nature.com/nrd/journal/v9/n11/full/nrd3251.html

Firewalled, but there is a great discussion at In The Pipeline that breaks out the numbers:

http://pipeline.corante.com/archives/2010/11/04/where_drugs_come_from_the_numbers.php

Of course more and more university research is funded by Pharma these days, especially the efforts that are most likely to lead to new drugs. Which column would you put that drug in?

ask anybody in The Biz anything with a buncha nitrogen tends to be a bit "frisky"

for example
http://pipeline.corante.com/archives/2013/01/09/things_i_wont_work_with_azidoazide_azides_more_or_less.php

is a compound that will go BOOM if you so much as look at it cross-eyed

Another one for the "The Anarchist Cookbook?" I wasn't aware of O2F2.. :-?

The formula that better describes its properties is FOOF. You can read a very entertaining description of its synthesis and properties here. Comparing FOOF to the stuff from "The Anarchist Coockbook" is like comparing Saturn 5 rocket to a firecracker. Yes they both blow up, but FOOF can make water explode at subzero temperatures. Here is a quote from Stern, AG, The Chemical Properties of Dioxygen Difluoride, JACS 1963:

It caused explosions when added to ice at 130-140K.

BTW I strongly recommend reading Derek's "Things I Won't Work With" blog. It is a lot of fun.

Another one for the "The Anarchist Cookbook?" I wasn't aware of O2F2.. :-?

The formula that better describes its properties is FOOF. You can read a very entertaining description of its synthesis and properties here. Comparing FOOF to the stuff from "The Anarchist Coockbook" is like comparing Saturn 5 rocket to a firecracker. Yes they both blow up, but FOOF can make water explode at subzero temperatures. Here is a quote from Stern, AG, The Chemical Properties of Dioxygen Difluoride, JACS 1963:

It caused explosions when added to ice at 130-140K.

BTW I strongly recommend reading Derek's "Things I Won't Work With" blog. It is a lot of fun.

Now, I'm not particularly good with metric, nor am I particularly experienced with engine repair (having done nothing more complex than replacing a water pump), but I would think 500C is a bit unusual for an engine to operate at. That's roughly 900F, well above the melting point of, say, lead, and getting close to that of aluminum or magnesium.

According to some brief googling, the typical operating temperature for an engine is under 250F (120C), and gasoline auto-ignites at 280C (540F). So by the time your engine block has reached 500C, you should already have run a good ways away.

Not to mention that, just by the name, tetraflouropropene sounds like a hard chemical to aerosolize, which is also a condition needed for it to release HF.

So to recap:
You first need to get your engine block to a temperature far beyond what it's designed to handle. Then you need to be in a crash violent enough to aerosolize a decent-sized organic compound, *and* that aerosol has to land on that engine. Finally, all the above has to happen in sufficient quantities to produce a dangerous amount of HF gas, which I will note is not quite as holyfuckballswereallgonnadie lethal as you seem to think (it is very dangerous, and rightly feared, but you aren't going to die from a milliliter of it).

Yeah, I'm fine with that. Can't be much more dangerous than gasoline, which can kill you under far less unusual circumstances.

Are you really blaming the FDA for doing what they were told by elected officials chasing the extreme (and IMHO Godless) end of the "Christian" vote?

The answer was "Of course" with an explanation why. A couple of posts later you wrote:

I should never have used a metaphor in a discussion with someone that pretends to be mentally retarded enough to take it literally :(

Oh look, petty name calling.

All I can say is that if you want discussion rather than "petty high school debate", then don't be the source of the problem.

As to the adversarial nature of this "discussion", it's worth noting the large number of people who just tell me what is self-evidently right. I'm far from perfect here, but it's not that common to see an actual "discussion" here. It's more common to see people just dump whatever opinions they think are true.

Way back when, "seven of five" posted this:

Since these folks enjoy the same public roads, military, police and fire protection, etc as everyone else, then they can help pay for them. Otherwise, they're just mooching off the public good. If it's too much to ask, they can move to some godforsaken island and fend for themselves. Libertarianism cuts both ways --- if you don't want to pay for the FDA, fine, but don't complain when your family members die from tainted medicine.

I was originally responding to the unwarranted assumption that the FDA saved lives. This is not a frivolous argument by me. There are blogs that speak of increasing costs and declining innovation in drug research over the past few decades.

It's reasonable to address one of the big factors causing that. Namely, regulatory agencies like the FDA which place a higher priority on safety of medical treatments than on the health of the people who would need those treatments.

accept only 5% of all that money is related to research

Do you have a citation for that number?

Most of the money for drug research comes from the public purse and the average US citizen is getting royally screwed by the drug companies for drug research they paid for already.

I assume you have been misled by the difference between "X looks like a great disease target" and "We now have an FDA-approved drug targeting X", and would like to suggest "In the pipeline" :

This is going to come across as nastier than I intend it to, but my first response is that the taxpayer's return on this was that they got a new drug where there wasn't one before. And via the NIH-funded discoveries, the taxpayers stimulated Pfizer (and many other companies) to spend huge amounts of money and effort to turn the original discoveries [...] into real therapies. I value knowledge greatly, but no human suffering whatsoever was relieved by the knowledge alone that JAK3 appeared to play a role in inflammation. What was there was the potential to affect the lives of patients, and that potential was realized by Pfizer spending its own money.

http://pipeline.corante.com/archives/things_i_wont_work_with/

Came for FOOF, leaving happy.

http://pipeline.corante.com/archives/things_i_wont_work_with/

Came for FOOF, leaving happy.

Different AC than the other, but I suggest selenophenol for all your somewhat-malicious odor generation needs.

Shockwatch labels that release sarin (or equivelent) gas when broken would incentivise good handling of the item.

No need to kill anyone. Some thioacetone would work just as well.

That "theory" is super-extra-stupid. Reactive oxygen species (ROS) are mostly generated in mytochondria and they never enter the blood stream (they are called 'reactive' for a reason!). Besides, it seems like ROS are actually _necessary_ - http://pipeline.corante.com/archives/2013/01/14/another_reactive_oxygen_paper.php

Having a fire on the beach and having the beach on fire are two completely different things

Time to share one of the most entertaining bits of chemistry writing that I've seen for ages : "It is also hypergolic with such things as cloth, wood, and test engineers, not to mention asbestos, sand, and water-with which it reacts explosively."

"Fun" stuff, for suitably small values of "fun".

It's by Derek Lowe, a pharmaceutical chemist who blogs about chemical compounds that are way too dangerous. His position is that the closest you want to get to any of these things is reading about them. The closest I want to get is reading what he has to say about them.

Take FOOF, aka F2O2, aka Dioxygen Difloride. Lowe calls it "Satan's kimchi".

The latest addition to the long list of chemicals that I never hope to encounter takes us back to the wonderful world of fluorine chemistry. I'm always struck by how much work has taken place in that field, how long ago some of it was first done, and how many violently hideous compounds have been carefully studied. Here's how the experimental prep of today's fragrant breath of spring starts:

"The heater was warmed to approximately 700C. The heater block glowed a dull red color, observable with room lights turned off. The ballast tank was filled to 300 torr with oxygen, and fluorine was added until the total pressure was 901 torr. . ."

And yes, what happens next is just what you think happens: you run a mixture of oxygen and fluorine through a 700-degree-heating block. "Oh, no you don't," is the common reaction of most chemists to that proposal, ". . .not unless I'm at least a mile away, two miles if I'm downwind." This, folks, is the bracingly direct route to preparing dioxygen difluoride, often referred to in the literature by its evocative formula of FOOF.

His latest posting is about the compound C2N14, which is two carbon atoms with 14 nitrogen atoms.

The compound exploded in solution, it exploded on any attempts to touch or move the solid, and (most interestingly) it exploded when they were trying to get an infrared spectrum of it. The papers mention several detonations inside the Raman spectrometer as soon as the laser source was turned on, which must have helped the time pass more quickly.

He doesn't just blog about things that go bang, he also covers things that smell really really bad. It's good he doesn't get stuck in a rut.

He has a fine turn with a descriptive phrase and a dry sense of humor. Check out his blog.

Pharma does a lot more than that. Try reading something like this, which is a blog by an actual medicinal chemist.

(yes kids, a match is a LOT of energy)

It takes more than an order of magnitude less energy to ignite hydrogen than to ignite hydrocarbon fuels. A match isn't necessary by any stretch of the imagination. Rubbing your feet across the carpet can produce 10-25 millijoules of energy, which is somewhere around 600-1500 times as much energy as is required to trigger hydrogen combustion in a hydrogen-air mixture, given the right concentration of hydrogen. No flame needed. I don't consider a couple hundredths of a millijoule to be a lot of energy, personally. When you're talking about explosion risk, I consider a lot of energy to mean at least kilojoules, and I'm not entirely comfortable with stuff that explodes with fewer than megajoules. :-)

Saying that it will start spontaneous combustion with air is Todd Akin levels of stupidity.

What I said was that it "pretty much spontaneously" combusts. That wording, in English, typically means that it doesn't, strictly speaking, spontaneously combust, but that it is really close. And I maintain the correctness of that statement. I mean, we're not talking Things I Won't Work With here, but you have to admit that working with it in industrial quantities wouldn't exactly be the highlight of any sane person's day.

Check out the thread over at In The Pipeline

http://pipeline.corante.com/archives/2012/08/14/reproducing_scientific_results_on_purpose.php

and

http://pipeline.corante.com/archives/2012/08/15/more_on_reproducing_scientific_results_organic_chemistry_edition.php