Derek Lowe

This is an amazingly hard problem and I wish you all the best. One thing you won't learn at school is all the complications involved in validating a target. The best resource I know of for this is the "in the pipeline" blog by Derek Lowe. I have spent 100s of hours reading all his posts (they go back 10 years) and especially the comments. It is a hard slog, but the amount you will learn is staggering. Edit. I guess is should include the link http://pipeline.corante.com/

There are several. One is forum on careers by sciencemag.org http://sciencecareers.sciencemag.org/ http://scforum.sciencecareers.org/ Also you can go to the following blogs which are interesting. http://pipeline.corante.com/

There is a problem with patent thickets in pharmaceuticals and biotech interfering with innovation, see Carlson's book Biology Is Technology for a good discussion of the problems there. A better alternative for pharmaceuticals may be for whoever puts it through trials to get a patent or license since that is by far the most expensive part for drugs. To an extent that is what has been happening with biotech startups inventing possible pharmaceuticals then their being purchased by large companies that develop them further and run the trials. If you are interested in drug development, http://pipeline.corante.com/ is an interesting blog to follow.

Many of the challenges Prasher faced were hardly unique to him. Scientific opportunities often appear only at specific times and places, potentially a serious impediment for a parent who doesn’t want to relocate the family. Do your work in the wrong place, or publish it in the wrong journal, and it may vanish without a trace. And once someone drops out of science, it is hard to get back in. Bad timing/luck was compounded by the fact that he was a bit of a loner and not driven to follow through on that area of research, even when given the opportunity to do so. One other issue that this story brings up: There are a lot of out-of-work postdocs and PhDs, owing to the major reduction in funding/grant opportunities and the consolidation taking place in certain industries, such as pharma. A very talented science blogger who covers this (as well as biochemistry research) is Derek Lowe -- I recommend bookmarking his blog at http://www.pipeline.corante.com/

An other neat one is "sand won't save you this time", from the delightful "Ignition!" via the Things I Won't Work With series (well worth reading in and of itself, even for non-chemists): http://pipeline.corante.com/archives/2008/02/26/sand_wont_save_you_thi…

That's nasty, but my favorite florene compound is still the apply named FOOF also known as "Satan's kimchi". http://pipeline.corante.com/archives/2010/02/23/things_i_wont_work_wit… "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" "When 0.2 (mL) of liquid 02F2 was added to 0.5 (mL) of liquid CH4 at 90°K., a violent explosion occurred." I mean how can't you love a substance that will violently detonate things at -180C.

My favorite is Hexanitrohexaazaisowurtzitane... "There's a recent report of a method to make a more stable form of it, by mixing it with TNT. Yes, this is an example of something that becomes less explosive as a one-to-one cocrystal with TNT." http://pipeline.corante.com/archives/2011/11/11/things_i_wont_work_wit…

Agreed. My favorite is still any post discussing Flouride bonds, particularly FOOF http://pipeline.corante.com/archives/2010/02/23/things_i_wont_work_wit…

This is a wonderful series that (rightfully) gets posted here a lot. I'd like to point out that the author's blog is also worth digging into for interesting and insightful posts about the modern pharmaceutical industry. For example: http://pipeline.corante.com/archives/2012/03/08/erooms_law.php (how knowing more has actually made us worse at finding effective drugs).

In the event that the permalink page isn't loading properly (his blog has been having problems lately), it looks like you can click to the main blog page and read it: http://pipeline.corante.com/

Derek Lowe's blog does cover that subject. You can find it at http://pipeline.corante.com/ including a sovaldi related post http://pipeline.corante.com/archives/2014/07/21/the_hep_c_field_gets_n…

The entire back catalogue for the Things I Won't Work With tag is extremely excellent, and well worth a read - http://pipeline.corante.com/archives/things_i_wont_work_with/

Another worrying development: Pfizer buying Astra-Zeneca. It's not to streamline drug development, the deal is a tax dodge in its entirety. Some lovely commentary down the hallway, in the Pipeline: http://pipeline.corante.com/archives/2014/04/28/pfizer_and_astrazeneca… Scientists worry about the cuts to NIH funding, but the cuts to pharmaceutical research are ten times more worrying - who is going to develop the compounds to replace the current set of antibiotics when they have become useless? Wall Street is entirely unequipped to deal with this question; there are things that cannot be bought with money or at market, and scientific progress is one of them.

The other articles in this series are worth a read too: http://pipeline.corante.com/archives/things_i_wont_work_with/ for a convenient list.

Followup http://pipeline.corante.com/archives/2013/04/05/chlorine_trifluoride_s…

Always worth a reread for the combination of gripping content with good writing. Just to pick another one in this series: http://pipeline.corante.com/archives/2008/02/26/sand_wont_save_you_thi… (about stuff that will burn sand (not: burn _in_ sand)

I loved this quote from http://pipeline.corante.com/archives/2011/11/11/things_i_wont_work_wit… Synthesizing polynitro compounds is no chocolate fondue party, either: if you picture a bunch of guys wheeling around drums of fuming nitric acid while singing the Anvil Chorus from Il Trovatore, you're not that far off the mark. You really have to beat the crap out of a molecule to get that many nitro groups on it, which means prolonged heating of things that you'd really rather not heat up at all.

Comments section of the original post is worth reading: http://pipeline.corante.com/archives/2013/03/28/xray_structures_of_eve…

This is a bit off-topic, but if you enjoyed his writing on this, I would also recommend perusing the category "Things I won't Work With"[1], but maybe only if you have the afternoon free. It's a hilarious compendium of chemicals that are simply too unpleasant to work with for his tastes. For values of unpleasant including explosive, smelly, corrosive, or some combination thereof. I'm not a chemist, but his tellings of not just how things could go terribly wrong once you have the substance, but the myriad ways it can wrong merely trying to make the substance had me in stitches for the better part of an afternoon. Then again, I was always the one setting stuff on fire, breaking glassware, or trying the reaction with more reagents in high school chem lab, so maybe it only appeals to me... [1] http://pipeline.corante.com/archives/things_i_wont_work_with/

My favourite is: http://pipeline.corante.com/archives/2008/02/26/sand_wont_save_you_thi… The compound also a stronger oxidizing agent than oxygen itself, which also puts it into rare territory. That means that it can potentially go on to “burn” things that you would normally consider already burnt to hell and gone, and a practical consequence of that is that it’ll start roaring reactions with things like bricks and asbestos tile.

http://blog.elphel.com/ image processing http://hydraraptor.blogspot.com/ 3d printers http://pipeline.corante.com/ pharmaceutical development http://howtospotapsychopath.com/ all sorts of stuff

This is an interesting point, and this very background may have found its way into the ruling. Specifically, that the judge has a background in chemistry and directly speaks to the difference in perspective between biologists and chemists : "We recognize that biologists may think of molecules in terms of their uses, but genes are in fact materials having a chemical nature and, as such, are best described in patents by their structures rather than by their functions" [1] The blogger goes on to state in more plain terms : "In other words, this ruling affirms that molecular biology is, in fact, chemistry, if you want to look at it that way." [1]http://pipeline.corante.com/archives/2012/08/17/the_myriad_gene_patent…

I'm not sure I'd call plutonium metal "not that dangerous" - it is pretty toxic, can catch fire spontaneously and once if does catch fire you have to be really careful trying to put the fire out. There is an excellent book on the history of the Rocky Flats nuclear weapons plant near Denver that describes some of the problems with handling plutonium on an industrial scale: http://www.amazon.com/Making-Real-Killing-Rocky-Nuclear/dp/0826327982 Edit: Of course these things are relative. I guess compared to chemicals like chlorine trifluoride or FOOF it is pretty tame from a chemical perspective: http://pipeline.corante.com/archives/2008/02/26/sand_wont_save_you_thi…

In The Pipeline[1] covers this well. http://pipeline.corante.com/archives/2011/04/01/live_long_and_prosper_… Researchers were speculating that if they could just bind something to defective proteins they could get them cleaned out of cells. Noting that they could see the defective structures because they were staining them yellow, they used their yellow stain. Instant 60% lifespan increase in (yellow) nematodes. If only nematodes could award Nobel prizes. Other non-dye chemicals were found to work similarly. If this goes anywhere in the end, I don't think we need to fear being ruled by an upper class of chartreuse immortals. [1] Best known around HN for the "Things I Won't Work With" series: http://pipeline.corante.com/archives/things_i_wont_work_with/

I love this series of blog posts, especially since I have studied a bit of organic chemistry and loved that lab work (a very one-sided love affair). As an old "fan" of rocket fuels in general and peroxides in particular, I still giggle a bit nervously at the chemical formula FOOF... Edit: http://pipeline.corante.com/archives/2010/02/23/things_i_wont_work_wit… "If the paper weren't laid out in complete grammatical sentences and published in JACS, you'd swear it was the work of a violent lunatic."

Older ones, yes. Newer ones use nitroguanidine and other less-toxic stuff according to the article you linked to. That said, we owe a lot to the brave chemists who manage to figure out how to deal with all these scary chemicals. Even if some of them are probably insane: http://pipeline.corante.com/archives/2010/02/23/things_i_wont_work_wit… I love how the chemical can be written as FOOF, which is strangely reminiscent of the bogus F00F C7C8 instruction that could crash old Pentiums.

The whole "things I won't work with" category is a good read: http://pipeline.corante.com/archives/things_i_wont_work_with/ along with the related category, "how not to do it": http://pipeline.corante.com/archives/how_not_to_do_it/

It's a very good question, and hardly a trivial one. Quite a lot of science is nearly worthless, and only published to pad the author's cv. A couple of blog posts on the topic: http://pipeline.corante.com/archives/2010/06/24/all_those_worthless_pa… http://pipeline.corante.com/archives/2010/06/25/what_to_do_with_the_no…

If anyone found this interesting, you should check out "In the Pipeline", a nice insider blog in the pharma industry: http://pipeline.corante.com/index.xml As a free bonus, his "Things I won't work with" sub-series is a great humor read about dangerous chemicals.

I love that particular subset of his blog. My favorite is still the entry on chlorine triflouride ( http://pipeline.corante.com/archives/2008/02/26/sand_wont_save_you_thi… ) This stuff is so nasty, it'll burn stuff that's already burnt. Oh, and there's no real way to put it out, so you just have to wait for it to finish eating through whatever was unfortunate enough to be in the vicinity when the spill happened.