Self-Destructing DRM on DVDs, Brought to You by Disney. Tear yourself away from the RIAA/Lawsuit story for just a moment, to check this out from Peter Henderson/Reuters: Disney to Test Self-Destructing DVDs This Week. For $6.99. Rather than rent, you can buy a copy that lasts 48 hours, so that you don't have to return it like a rental. If Walt Disney Co. gets its wish, an experimental type of DVD will begin flying off store shelves on Tuesday -- and self-destructing 48 hours... [bIPlog]

I don;t understand. For a little less than half what you can get a recently released DVD for, you get one that only lasts 48 hours and has no extras (I am a DVD-freak but by judicious buying, my average price for a DVD is about $11, counting tax and/or postage). You had better hope you NEVER want to watch the movie again. Plus all the SD-DVDs that would end up in landfills. But I guess for the idiots who run up big late fees, it will be a boon. because only an idiot owuld go for this. Maybe if the price point was $3 but $7? Unbelievable.  11:35:20 PM    

Flash Mob For Dean

11:27:52 PM    

'Tis Folly To Be Wise

I came across an article in my files today that I thought I'd share. It's by the late Calvin Mooers, an information scientist. He addressed his colleagues on the question of why some information systems got so much more use than others - often with no correlation between the amount of use and how useful the tools actually were.

"It is my considered opinion, from long experience, that our customers will continue to be reluctant to use information systems - however well designed - so long as one feature of our present intellectual and engineering climate prevails. This feature - and its relevance is all to commonplace in many companies, laboratories, and agencies - is that for many people it is more painful and troublesome to have information than for them not to have it."

When I first read this, I experienced that quick shock of encountering something that you feel as if you'd known all along, without realizing that you knew it. Of course. It's not a new idea, but we keep having to learn it over and over. Mooers again:

"Thus not having and not using information can often lead to less trouble and pain than having and using it. Let me explain this further. In many work environments, the penalties for not being diligent in the finding and use of information are minor, if they exist at all. In fact, such lack of diligence tens often to be rewarded. The man who does not fuss with information is seen at his bench, plainly at work, getting the job done. Approval goes to projects where things are happening. One must be courageous or imprudent, or both, to point out from the literature that a current laboratory project which has had an extensive history and full backing of the management was futile from the outset."

Oh, yes. Yes, indeed. I've seen these examples made real right in front of my eyes, and more than once. Have I mentioned that Mooers wrote all this in 1959? The problem has not lessened one bit since then. If anything, our vast information resources and the powerful tools we have to dig for it have made things worse. Just try being the person who finds a patent claim that stops a project in its tracks, one that was missed while the work went on for months. Or find out that a close analog of the lead compound was found to be toxic twenty years ago.

We're supposed to be able to find these sorts of things. But everyone assumes that because it's possible to do it, that it's been done. Taken care of: "Didn't we see that paper before? I thought we'd already evaluated that patent - isn't that one one that so-and-so found? It can't be right, anyway. We wouldn't have gone this far if there were a problem like that out there, clearly."

My rule, which I learned in graduate school and have had to relearn a few times since, is to never take anything on faith when you join a new project. Go back and read the papers. Root through the primary literature. Look at the data and see if you believe it. If you let other people tell you what you should believe, then you deserve what you get when it comes down around your ears.

[Corante: In the pipeline]

Derek has some really important insights that balance mine quite well. He is a medicinal chemist, with a mind for synthesis pathways and process. I did my postdoc in the lab of Marvin Caruthers in Boulder, whish was involved in developing the chemistry that allows large scale DNA synthesis to be done. I am probably one of the few biologists who actually synthesized oligonucleotides by hand in sintered glass funnels. You could make about a 14-mer before your liver got overloaded from the fumes, even in a hood, and you acted like you were 9 days drunk.

The nice thing about chemistry is that once a protocol is figured out, it is pretty well set. If you are supposed to get 85% yield and you get 25%, you screwed up. In biology, protocols are much more of a gossamer nature. I can follow the protocol to add a DNA sequence to some bacteria, using the same samples, on two different days, and get very different results. Has nothing to do with my abilities. It has more to do with attempting to control a complex system. This difference in outcome is something that frustrates many chemists but is a given for any biologist.

But the tendency NOT to read the literature seems to be endemic, whether you are a linear, process driven scientist, or some New Age freewheelin' biologist. I was continually amazed because I would always go and look to see what others had done. Why repeat someone else's success? Yet I would get hammered for spending time in the library instead of doing benchwork. By doing that I was able to save the company over $50,000 a year at a time when that was a lot of money for us. I would still get hammered. I guess some of these guys feel that if it was important they would already have heard of it. Since they had not heard of it, and now they thought it was important, it must not have been done. Faulty premises lead to a lot of really bad science.   9:54:45 PM    

Everything You Know is Wrong

I mentioned that I've had to learn the lesson, more than once, that you shouldn't trust other people to know more about your research than you do. That's one of my "Lowe's Laws of the Lab," actually: Your Project Is In Big Trouble If Other People Know More About It Than You Do.

There was an experience early in my research career that got me on that path. I had been asked, as a student, to make a cyclic compound as a test system to look at some unusual reactions. There was a synthesis worked out for me; I looked it over and it didn't seem obviously crazy, so I went with it. (Keep in mind that I knew some organic chemistry, but certainly not as much as I could have used.) These compounds hadn't been made before, so I was willing to take a crack at them.

First step, not too bad. Second step, no problem. Third step. . .needed to be fixed a bit. It was a reduction of a triple bond to a double bond, which calls for the more mystical end of the hydrogenation catalyst field (one whose mainstream was accurately described to me in my first organic course as "witchcraft.") But I got it to work: an old-fashioned Lindlar catalyst, plus some quinoline to make it even less reactive. It's the sort of reaction that a chemist in 1952 would have felt very comfortable with. But those reaction still work just fine - it's one of the things I like about chemistry, that good reactions never go out of style.

So far, so OK. Now it came time for a ring closure, making a cyclic ether, and the way that my betters had mapped out for me was to use something called the Mitsunobu reaction. My fellow organic chemists will start to hear the faint sound of alarm bells right about now, because that's not the most reliable method for that sort of thing. For many kinds of rings, there isn't a most reliable method for that sort of thing, but you can usually hack something out.

Except in this case, and for good reason. Shop talk for my colleagues: you'll have to remember that I was very early in my career when I tell you that one of the reacting centers was neopentyl. For those outside the field, that means that the Mitsunobu reaction, and a host of others that depend on the same sort of attack, was doomed from the start. The two end of the chain I was trying to link together were too lumpy and crowded; I'd have been lucky to get it to work in a diamond anvil under geologic pressures.

Well, it took a little while for this realization to creep up on me, but it finally got my attention, and I sat down to think about why I was wasting my time like this. Surely someone had made ugly hindered cyclic ethers before? I went down to the bound volumes of Chemical Abstracts, and this was before the days of access to computer-based searching of that mighty database. Not long before - by the next year, I was sitting in front of a terminal doing ASCII-based structure searching - but there was no way at the time to do it than by hand.

It's a lost art, and it deserves to be a lost art. One semi-effective way was to find the name of your parent system of interest, and to cruise down the columns in the Name Index, looking for likely compounds in their alphabetic ranks. My cyclic ether was easy to localize, and I started down the list. . .and it wasn't long before, to my complete consternation, I found the exact compound I was trying to make.

But hold on - this was a new compound, right? What was it doing in Chemical Abstracts? Well, it was presented to me as a new compound, because (as it turned out) no one had bothered to see if it had ever been made before. I jotted down the reference number, hopped immediately over to the abstract volume (you used to have to do that, folks,) and from there to the original paper itself. I still have the copy of it that I made that night.

It's in my files, turning a bit yellow around the edges after twenty years or so. I'll never throw it away. These folks had made the compound I needed, in one step, from two things that you could buy from the Aldrich catalog. They used a reaction I'd actually never heard of, which made me feel a bit better (at least I hadn't missed something I supposedly knew.) But there was my last few weeks of on-and-off work (I was taking classes, too,) which could have been accomplished in an afternoon if I'd had the sense to look the thing up before I started. If I'd had the sense not to just take what was handed to me, that is. Believe me, you deserve what you get. My career since then has been an effort to get as little of it as I can.

[Corante: In the pipeline]

Memories. Doing literature searches is one of the most important lessons most of us learn doing our graduate work. You are scared to death that someone else is working on the same thing and is further ahead. You look for clues in the published literature, sure that their paper has been published in some obscure journal, just to make you more paranoid.

In the pre-Internet days, you had to do these searches by hand. There was Chem Abstracts and Index Medicus. You would get the year-end indices from Science, Nature, etc. and hope you could find a review article. Those were gold, becuase the reference list lead you directly to the article you needed. You could then spread from there and hope to find some link to the knowledge you needed. Almost all of us did something similar during our graduate days.

Yet, when we become a professional, many never do a literature search again. In today's world this is ridiculous. I have not used Chem Abstracts or Index Medicus in 10 years. Online searching is too easy. I can find out what is going on in a field so rapidly know that I just smile when thinking of the old days. So I just do not understand why so many scientists never do this. They may rely on someone in the library to send them the results of a weekly search in 'Cytokines' but never much on their own. I just shake my head.  9:51:43 PM