catbirdseat

A drug that I worked on in the late 1980's was finally approved by the FDA for use in the United States to treat Parkinson's Disease. The following is probably only of interest to tech geeks so be forwarned. I'm posting this because this approval is very gratifying to me, even though I left the project almost 20 years ago. My grandfather died of Parkinson's complications in 1983. Mohammed Ali suffers from this disease. It is a horrible disease. Neupro is the brand name for the rotigotine patch. The drug had its origin at a company called Nelson Research, founded by Eric Nelson on the UC, Irvine campus as a sort of spin off of Allergan Pharmaceuticals. I hired on there in 1986 under Richard Phillips. We built up an analytical services group from scratch. The earliest form of the drug was designated N-0437 (2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin). It was racemic (mixture of two optical isomers). The drug was found to be very potent. A stereoselective synthesis was developed for the active (-) isomer, which was then designated N-0923. This was twice as potent as N-0437. N-0923 was so potent its active dose was about a milligram, and plasma concentrations were on the order of a mcg/mL. I worked on a sensitive HPLC method using electrochemical detection so we could conduct pharmacodynamic studies in monkeys and later humans. They had a rather interesting way of testing the drug. They'd induce "hemi-Parkinson's" in monkeys by giving MPTP to one side of the brain and selectively killing off the dopamine producing cells in the substantia nigra of only that side of the brain. One side of the monkey was paralyzed and the other normal. The monkeys could only turn towards the paralyzed side. They never turned the other way. If you gave an effective dose of drug, the monkey could turn either way as a normal animal would. They'd have people watching with clicker counters. One for left and one for right. Subract the left count from the right count and you'd have the net turns. You were shooting for a net of zero. One of the hallmarks of N-0923 was "first pass metabolism", that is it goes directly from the gut, where it is absorbed, to the liver where it is metabolised. Because of this, the half life of the drug was very short indeed. The drug could have died here but it didn't. It was pure serendipity that Nelson Research was experienced in dermal drug delivery and it occurred to them to try administration by skin as opposed to the oral route. This avoids first pass metabolism. It so happened that the drug was really well absorbed through the skin and the idea of a patch was discussed. Nicoderm had been recently introduced at this time, so patches were all the rage, as it were. One of the interesting things about this drug, a Dopamine D-2 Agonist, was that it not only reduced Parkinson's symptoms it made people feel REAL GOOD. In tests on rats it was much more addicting than cocaine. You'd think this would have killed the drug's chances, but did not because of two factors. Patches provide steady state levels, which tends to reduce addiction. Second, patients were generally old people with severe disease poorly treated by existing drugs (including L-Dopa). Nelson was bought by Ethyl Corporation around 1988 and the name was changed to Whitby Pharmaceuticals. In 1990, quite abruptly, Ethyl decided they wanted to move the company to Richmond Virginia. I gave serious consideration to making the move but decided against it as Richmond would be a bad place to find oneself out of work as a chemist. This was where I parted company and soon ended up in Seattle. About half of my colleagues made the move to Richmond where they worked for about a year when Ethyl decided to get out of pharmaceuticals and let everyone go. A group of scientist from Whitby got together and started their own company Discovery Therapeutics and bought from Ethyl the patent for N-0923. They labored through the 1990's on N-0923 which eventually was issued the generic name rotigotine by the FDA. Discovery eventually entered into a partnership with Schwarz Pharma, a Swiss company, since the costs of full scale clinical trials are beyond what a small company could afford. So now here it is 2007 and the drug is finally approved in the US, about 22 years after it was first synthesized by a chemist. It's a long road. Is it any wonder drugs cost as much as they do?

It would seem that Larry is not around much these days. A couple weeks ago, I saw a party camped with pitched tent in the woods near Icicle Buttress. They were in plain sight camped two nights in the same place.

Extending that first piece with a long runner will tend to protect only that piece from the zipper effect. It will in fact increase the chance that pieces above will zipper out. Much better to make sure that first piece is omni-directional and sling it short.

My son was told by Dave Marriot that Marsalis is not currently promoting a new release, but just touring for its own sake. This means one can expect a good mix of his music both new and old. One might even hear unreleased material.

Placing too much gear can mean pumping out and not sending. But I find as I become more experienced, I can place gear faster and in places I wouldn't have found it before. I can place it from stances that I wouldn't have considered rests before. I guess there are two approaches to protecting. One mind set is to protect in such a way that injury is completely prevented in ANY fall. The other approach is to place it such that catastrophic injury or death is prevented, but some injury is certain in a fall. I'd like to think that in the latter case, the climbing is easy enough that a fall is pretty darn unlikely. Again, with experience we can better judge the likelihood of a fall.

Humans could help the pika by relocating colonies of them to more northern mountains formerly too cold to inhabit. They have no way of spreading on their own.

Here he is doing a old time New Orleans Dixieland number called Royal Garden Blues. http://www.youtube.com/watch?v=bgZOHevbXbk When they get into the solo section you have no doubt this is the 21st Century.

Anyone else going to see Branford Marsalis at Jazz Alley? It should be a good show.

There was an article in the PI this morning about this. I think at first glance it's a good idea, but then they mentioned how the largest units have a tip velocity of 40 knots. That would be enough to make mince meat of any fish that happens along.

Rudy, I've been meaning to talk to you about that tie in knot you've been using. It's waaayyy sketch.

I know very few climbers who participate in trail projects. They all have other more important things to do. As a result they have very little influence on the projects that get done and how they are done. By getting involved with the Everett Mountaineers Trails group I was able to persuade them to take on the Three O'clock Rock trail last year. The entire crew of 75 spent the entire day and improved the trail from the trailhead all the way to the rock. Matt and Mark were there too. I'm going to try to get the Mountaineers to devote two crews of ten again this year.

Heavens, no. I thought that was the clincher.

That's a brilliant piece of writing. I'm sure Arnold will be swayed by your persuasive arguments.

Muffy? That is to say you think she is BOTH the best and the worst at the same time? That seems like a contradition, but maybe not.

What? No plug for Zeros? What's up with that?

I did Friday's Jinx year ago and thought the pro was bomber.....if you are experienced, I could tell that some of the gear placements were tricky it was not a beginner route. Great second pitch. So can you elucidate on "tricky"? I imagine the cracks have lots of flaring sections or irregularities so that cams have to be positioned precisely to hold?

Damn right. I like my funny hats.

Sounds like they could have done everyone (who was not on the road) a favor and given her the damn keys. They could have been gentlemen and offered to drive her to her Meth dealer.

It is that book. Just click on the link.

No one has the ability to give away his true identity so surely and quickly as that fellow.

Why is it then that some people have to crowd around a victim while others show some respect and mind their own business (unless of course they are actually aiding someone that is). Case in point the woman who injured her ankle at Stone Gardens. People were following the paramedics to go gawk at the poor woman. Clearly they weren't going to help. I was curious but I decided not to follow the crowd. I didn't want to add to the embarrassment the person must have been feeling.

I dont' think a single one of your points is true. 1) Light rail is faster than a bus, so more people would use it for longer commutes because it compares to the speed of a car. 2) Light rail is only vastly more expensive if you don't count the money spent on the roads that the buses use. You are only counting the incremental cost of more busses. 3) Light rail can handle much greater numbers of people than a bus. The idea of rail is that growth follows the line rather than the line following growth.

It beats being cold. That is a very warm hat.

Jason, these people live fake lives. They view this as a chance to experience something real. You live life fully through climbing, so it's different for you. You know what life and death is. These people only know what they see on television.