It looks like the NIH is going to start screening for new drugs. Here’s a quick and dirty primer on how drug discovery works (via me):
There are two different paths to discovering a drug. In the first path, a database of gene sequences are scanned for a potential “target”. The target gene codes for a protein or receptor that is implicated in a disease state. Biologists make the protein and use robots to test a library of potential “ligands”, drug compounds, against the target. These libraries consist of hundreds of thousands and possibly millions of compounds. When a compound interacts with the target and elicits the right response, it is called a hit. The hits are passed to a project team of biologists, chemists and drug designers who examine the hits, select the most promising ones, ie, the ones that look like they won’t be toxic or too hard to work with and which provide places for modification. The team then engages in a years long struggle of iterations. The drug designers propose modifications, the chemists make the modifications the designers suggest (or not, as the case may be. Convincing a chemist to make a drug is the most challenging aspect of the whole endeavor, IMHO.) and the biologists test the new compounds and say “hotter” or “colder”.
There is a lot of other stuff going on in the background. There are structural biologists who can sometimes crystallize the protein in question and make it a lot easier for the chemist and designers to see what the hell they’re doing. Also, there are groups that test the compounds for properties other than how effective they are against the target. Those things include toxicity, mutagenicity (how likely they are to cause cancer and birth defects), bioavailability (how easily they get into your system through the gut, stomach or blood-brain barrier), solubility (how easily they dissolve), metabolism (how your liver breaks them down and into what byproducts) and cardiotoxicity (does it make your heart spazz out). Note that this list is not exhaustive. The FDA is very strict about what goes into your body and drug discovery takes these regulations very seriously.
Once the potential new drug is ready, it gets passed to a development group for scale up and clinical trials. This whole process takes a long, long, LONG time and there are many failures along the way. It is also extremely expensive.
The other path is to bypass the gene target identification route and simply test a bunch of compounds, that are already sitting around, against a desired endpoint. This is known as a phenotypic screen or high content screening. In this case, the drug company does not know what the target is, well, not at first. Instead, the tests that are conducted against cells and a desired outcome is noted. After the phenotypic screen finds hits, it is sometimes possible to deconvolute the pathway that the compound affected and identify the targets. In this scheme, the discovery process presumably starts out with drug compounds in the library that are already known to have desirable or promising safety profiles because they might have been worked on before for different projects but they weren’t active enough against the target they were made for. But that doesn’t mean they can’t be used for something else.
The last pathway is what I think is going on with this new initiative at the NIH or at least that’s the way I interpret it.
There’s a lot of factual data in the NYTimes article about what the drug industry is up against. It remains to be seen whether this new initiative will be good or bad for the industry or the public. I can imagine many possible scenarios as to how it might turn out and some worry or encourage me more than others.
In any case, go read it and when you’re done, I’ll try to answer any questions you might have in a broad, general way. I can’t speak for my industry or company and wouldn’t want to anyway. But general information I can do.
Update:
Here’s a weird comment from the same article:
Great. So now taxpayers will be liable when there’s a problem. I hope there’s some kind of handoff program to private industry at some point in the program to avoid problems like that.
Soooo, let me get this straight. The ability to sue is still of utmost importance. Did I get that right? Because, from where I sit, the class action lawsuits are part of the problem. Everyone complains about not reining in the big finance guys but ambulance chasers looking for big bucks who glom onto adverse drug reaction reports like blood sucking ticks are all ticketyboo? It’s *not* ok to curb the lawyers? I mean, presumably, the government would not be interested in deliberate negligence and injury brought on by a joint venture, right?
Just curious.
Another commenter who doesn’t quite get how the industry works or didn’t check the graphs on the side of the page (they are pretty accurate):
Its about time. Our drug companies have lost focus on what is really important. All they concentrate on is profit and the FDA is complicit in its approval process. New drug application fees should be abolished also. One drug turns into 5 or 6 all with patents and huge costs are passed on to the US consumer. We do not need over half of these meds for they really do not benefit anyone other than the profits of big pharma. Do we actually need dozens of antidepressants or drugs for male impotence?
I’ve seen many good drugs taken off the market because of unexpected side effects. It happens to all of the companies in the industry. I’ve also seen drugs that the industry has spent billions of dollars and years to develop go before the FDA and get shot down. There goes a huge investment. It’s hard to justify taking that kind of risk with shareholders’ money, especially when money making drugs are going off patent and there’s nothing in the pipeline that can get approved. If the FDA and the pharmaceutical companies are colluding with each other, you would expect a whole lot more drugs getting approved and the numbers simply don’t bear that out. Sooo, I would safely ignore this commenter as dreadfully uninformed.
Filed under: General | Tagged: drug discovery, how drugs are made, NIH, pharmaceutical companies | 43 Comments »