About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
Not Voodoo

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
Realizations in Biostatistics
ChemSpider Blog
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Eye on FDA
Chemical Forums
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa

Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
Gene Expression (I)
Gene Expression (II)
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net

Medical Blogs
DB's Medical Rants
Science-Based Medicine
Respectful Insolence
Diabetes Mine

Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem

Politics / Current Events
Virginia Postrel
Belmont Club
Mickey Kaus

Belles Lettres
Uncouth Reflections
Arts and Letters Daily

In the Pipeline

Category Archives

November 3, 2014

Job Interview Advice

Email This Entry

Posted by Derek

I find it very refreshing to be talking again, once in a while, about finding jobs in drug discovery. Via my Twitter feed, I note this fine article from Linda Wang in C&E News about job interviews. It's a very picky world out there in the job market (still not so many jobs, still a lot of good candidates), and this is very useful reading for people on the interview trail. (It appears, for example, that the good ol' put-'em-on-the-spot technique is not dead). I've never liked that one, although I don't have much better to offer, either - I've noticed over the years that I'm not very good at predicting how people will be from just an interview. Is anyone?

This book, just out, could be another resource: it's called Navigating the Path to Industry, and it's especially aimed at academic scientists (not just entry-level ones, either) who are looking at industrial research positions. That's always seemed like an alternate universe to a lot of people, and this book should fill a gap.

Comments (37) + TrackBacks (0) | Category: Book Recommendations | How To Get a Pharma Job

September 2, 2014

What If?

Email This Entry

Posted by Derek

I wanted to let readers know of a fun new book that's out this week. Randall Munroe, of webcomic XKCD fame, has written What If?: Serious Scientific Answers to Absurd Hypothetical Questions. There are a lot of truly odd ones in there, and he takes them on as best he can. I'm glad to say that I'm quoted in the chapter on "What would happen if you made a periodic table of cube-shaped bricks, where each brick was made of the corresponding element?" (That should give you an idea of the sorts of questions that come in to him; it makes my mail look fairly sane by comparison). And no, you wouldn't want to do that one - consider astatine and francium, for starters.

Comments (11) + TrackBacks (0) | Category: Book Recommendations

May 30, 2014

A New Med-Chem Reference

Email This Entry

Posted by Derek

Over the past few years, several readers here have recommended Silverman's medicinal chemistry book as an excellent introduction and reference. I wanted to mention that there's now a third edition: The Organic Chemistry of Drug Design and Drug Action, by Silverman and Holladay, which has just come out. Well worth a look for that part of the bookshelf.

Comments (11) + TrackBacks (0) | Category: Book Recommendations

February 3, 2014

A New Book

Email This Entry

Posted by Derek

Noted as a significant new book relevant to biopharma, but necessarily without any comment from me is Barry Werth's The Antidote: Inside the World of New Pharma, which is the sequel to his 1995 book, The Billion Dollar Molecule. The official release date is tomorrow.

Comments (23) + TrackBacks (0) | Category: Book Recommendations

December 20, 2013

Holiday Blogging

Email This Entry

Posted by Derek

Starting today, blogging here will move to the irregular holiday schedule. Look for recipes and the like over the next couple of weeks, interspersed with occasional relevant topics as they come up. I hope everyone with a break has a good one - I'll be working The Chemistry Book and the Things I Won't Work With collection (as well as lounging around, naturally).

I'd also like to thank everyone who's bought through the Amazon links in the "Science Gifts" posts I've put up in the last couple of weeks. The commission loot is very much appreciated, and I pledge to use it wisely. Fairly wisely.

Comments (7) + TrackBacks (0) | Category: Book Recommendations

December 3, 2013

Science Gifts: Running Experiments at Home

Email This Entry

Posted by Derek

Interesting science-gift ideas can be found in the "home experiments" area. There's been a small boom in this sort of book in recent years, which I think is a good thing all the way around. I believe that there's a good audience out there of people who are interested in science, but have no particular training in it, either because they're young enough not to have encountered much (or much that was any good), or because they missed out on it while they were in school themselves.

Last year I mentioned Robert Bruce (and Barbara) Thompson's Illustrated Guide to Home Chemistry Experiments along with its sequels, the Illustrated Guide to Home Biology Experiments and the Illustrated Guide to Home Forensic Science Experiments. Similar books are Hands-On Chemistry Activities and its companion Hands-On Physics Activities.

Related to these are two from Theodore Gray: Theo Gray's Mad Science, and its new sequel, Mad Science 2. Both of these are subtitles "Experiments that you can do at home - but probably shouldn't", and I'd say that's pretty accurate. Many of these use equipment and materials that most people probably won't have sitting around, and some of the experiments are on the hazardous side (which, I should mention, is something that's fully noted in the book). But they're well-illustrated from Gray's own demonstration runs, so you can at least see what they look like, and learn about the concepts behind them.

And there's copious chemistry available in a series of books by Bassam Shakhashiri, whose web site is here. These are aimed at people teaching chemistry who would like clear, tested demonstrations for their students, but if you know someone who's seriously into home science experimentation, they'll find a lot here. The most recent, Chemical Demonstrations, Volume 5, concentrates on colors and light. The previous ones are also available, and cover a range of topics in each book: Volume 4, Volume 3, Volume 2, and Volume 1.

Comments (5) + TrackBacks (0) | Category: Book Recommendations | Science Gifts

November 21, 2013

The Chemistry Book

Email This Entry

Posted by Derek

I wanted to mention to readers here that I've agreed to write a book (for a general audience) on chemistry for Sterling Publishers (the publishing arm of Barnes and Noble). They've been putting out a series of books (Sterling Milestones) on various scientific topics, looking at 250 key concepts or historical events. There's a short essay on each of these, and an illustration on the facing page. Clifford Pickover did The Math Book, The Physics Book, and The Medical Book for them, and recently they've published The Drug Book, The Space Book, and The Psychology Book as well. So I'm doing The Chemistry Book, which occupies me on my train rides home after work and after dinner - my wife and kids have been involuntarily roped in as the test audience for the entries.

The book itself won't be out for a while - I'm delivering the manuscript next spring, and there will surely be a lot of editorial work after that. I have over 200 of the short chapters outlined so far, but I'm leaving some room for more topics as they occur to me (and as the chapters I'm writing suggest - sometimes I find that I have to include another topic to make the one I'm working on make sense to the eventual readers).

I don't want to give away the complete list of chapters just yet, not least because it's still changing around, but I would like to solicit nominations for events and ideas that anyone thinks I should be sure to cover. The book spans the whole historical record, up to the present day, in all fields of chemistry, so in one sense the challenge is narrowing it down to just 250 short essays. The other challenge is actually writing 250 short essays, of course. I'm doing OK against my list so far, but there are some topics that are difficult to do justice to in 350 words, as will be easily appreciated by the chemists around here.

So if anyone has some topics, obvious or nonobvious, that they think a book like this should be sure to include, please mention them in the comments. I'm sure some of them will already be on the list, but since I have room to add more, I certainly don't want to miss too many good opportunities. Thanks very much!

And yes, the "Things I Won't Work With" manuscript is being worked on as well. "The Chemistry Book" is giving me some practice at integrating a longer manuscript, and I've been adding some new material along the way. The trickier part of that one has been getting rid of some repetition that you notice when the original blog posts are stacked up together. But it's definitely in the hopper.

Update: a lot of good ideas in the comments! Many of them were already on my list, but I've already seem some that I wouldn't have thought of, and some others that I really should have but overlooked. Much appreciated! Anyone who hasn't added something and still wants to, though, feel free - I'll be checking this post pretty frequently.

Comments (146) + TrackBacks (0) | Category: Book Recommendations

May 2, 2013

E. O. Wilson's "Letters to a Young Scientist"

Email This Entry

Posted by Derek

I've been reading E. O. Wilson's new book, Letters to a Young Scientist. It's the latest addition to the list of "advice from older famous scientists" books, which also includes Peter Medawar's similarly titled Advice To A Young Scientist and what is probably the grandfather of the entire genre, Ramón y Cajal's Advice for a Young Investigator. A definite personal point of view comes across in this one, since its author is famously unafraid to express his strongly held opinions. There's some 100-proof Wilson in this book as well:

. . .Science is the wellspring of modern civilization. It is not just "another way of knowing", to be equated with religion or transcendental meditation. It takes nothing away from the genius of the humanities, including the creative arts. Instead it offers ways to add to their content. The scientific method has been consistent better than religious beliefs in explaining the origin and meaning of humanity. The creation stories of organized religions, like science, propose to explain the origin of the world, the content of the celestial sphere, and even the nature of time and space. These mythic accounts, based mostly on the dreams and epiphanies of ancient prophets, vary from one religion's belief to another. Colorful they are, and comforting to the minds of believers, but each contradicts all the others. And when tested in the real world they have so far proved wrong, always wrong.

And that brings up something else about all the books of this type: they're partly what their titles imply, guides for younger scientists. They're partly memoirs of their authors' lives (Francis Crick's What Mad Pursuit is in this category, although it has a lot of useful advice itself). And they're all attempts to explain what science really is and how it really works, especially to readers who may well not be scientists themselves.

Wilson does some of all three here, although he uses examples from his own life and research mainly as examples of the advice he's giving. And that advice, I think, is almost always on target. He has sections on how to pick areas of research, methods to use for discovery, how to best spend your time as a scientist, and so on. The book is absolutely, explicitly aimed at those who want to make their mark by discovering new things, not at those who would wish to climb other sorts of ladders. (For example, he tells academic scientists "Avoid department-level administration beyond thesis committee chairmanships if at all fair and possible. Make excuses, dodge, plead, trade." If your ambition is to become chairman of the department or a VP of this or that, this is not the book to turn to.

But I've relentlessly avoided being put onto the managerial track myself, so I can relate to a lot of what this book has to say. Wilson spent his life at Harvard, so much of his advice has an academic slant, but the general principles of it come through very clearly. Here's how to pick an area to concentrate on:

I believe that other experienced scientists would agree with me that when you are selecting a domain of knowledge in which to conduct original research, it is wise to look for one that is sparsely inhabited. . .I advise you to look for a chance to break away, to find a subject you can make your own. . .if a subject is already receiving a great deal of attention, if it has a glamorous aura, if its practitioners are prizewinners who receive large grants, stay away from that subject.

One of the most interesting parts of the book for me is its take on two abilities that most lay readers would take as prerequisites for a successful scientist: mathematical ability and sheer intelligence in general. The first is addressed very early in the book, in what may well become a famous section:

. . .If, on the other hand, you are a bit short in mathematical training, even very short, relax. You are far from alone in the community of scientists, and here is a professional secret to encourage you: many of the most successful scientists in the world today are mathematically no more than semiliterate.

He recommends making up this deficiency, as much as you find it feasible to do so, but he's right. The topic has come up around here - I can tell you for certain that the math needed to do medicinal chemistry is not advanced, and mostly consists of being able to render (and understand) data in a variety of graphical forms. If you can see why a log/log plot tends to give you straightened-out lines, you've probably got enough math to do med-chem. You'll also need to understand something about statistics, but (again) mostly in how to interpret it so you aren't fooled by data. Pharmacokinetics gets a bit more mathematical, and (naturally) molecular modeling itself is as math-heavy as anyone could want, but the chemistry end of things is not.

As for intelligence, see what you think about this:

Original discoveries cannot be made casually, not by anyone at any time or anywhere. The frontier of scientific knowledge, often referred to as the cutting edge, is reached with maps drawn by earlier investigators. . .But, you may well ask, isn't the cutting edge a place only for geniuses? No, fortunately. Work accomplished on the frontier defines genius, not just getting there. In fact, both accomplishments along the frontier and the final eureka moment are achieved more by entrepreneurship and hard work than by native intelligence. This is so much the case that in most fields most of the time, extreme brightness may be a detriment. It has occurred to me, after meeting so many successful researchers in so many disciplines, that the ideal scientist is smart only in an intermediate degree: bright enough to see what can be done but not so bright as to become bored doing it.

By "entrepreneurship", he doesn't mean forming companies. That's Wilson's term for opportunistic science - setting up some quick and dirty experiments around a new idea to see what might happen, and being open to odd results as indicators of a new direction to take your work. I completely endorse that, in case anyone cares. As for the intelligence part, you have to keep in mind that this is E. O. Wilson telling you that you don't need to be fearsomely intelligent to be successful, and that his scale for evaluating this quality might be calibrated a bit differently from the usual. As Tom Wolfe put it in his essay in Hooking Up, one of Wilson's defining characteristics has been that you could put him down almost anywhere on Earth and he'd be the smartest person in the room. (I should note that Wolfe's essay overall is not exactly a paean, but he knows not to underestimate the guy).

I think that intelligence falls under the "necessary but not sufficient" heading. And I probably haven't seen that many people operate whom the likes of E. O. Wilson would consider extremely smart, so I can't comment much on what happens at that end of the scale. But the phenomenon of people who score very highly on attempted measures of intelligence, but never seem to make much of themselves, is so common as to be a cliché. You cannot be dumb and make a success of yourself as a research scientist. But being smart guarantees nothing.

As an alternative to mathematical ability and (very) high intelligence, Wilson offers the prescription of hard work. "Scientists don't take vacations", he says, they take field trips. That might work out better if you're a field biologist, but not so well for (say) organic chemistry. And actually, I think that clearing your head with some time off actually can help out a great deal when you're bogged down in some topic. But having some part of your brain always on the case really is important. Breaks aside, long-term sustained attention to a problem is worth a lot, and not everyone is capable of it.

Here's more on the opportunistic side of things:

Polymer chemistry, computer programs of biological processes, butterflies of the Amazon, galactic maps, and Neolithic sites in Turkey are the kinds of subjects worthy of a lifetime of devotion. Once deeply engaged, a steady stream of small discoveries is guaranteed. But stay alert for the main chance that lies to the side. There will always be the possibility of a major strike, some wholly unexpected find, some little detail that catches your peripheral attention that might very well, if followed, enlarge or even transform the subject you have chosen. If you sense such a possibility, seize it. In science, gold fever is a good thing.

I know exactly what he's talking about here, and I think he's completely right. Many, many big discoveries have their beginnings in just this sort of thing. Isaac Asimov was on target when he said that the real sound of a breakthrough was not the cry of "Eureka!" but a puzzled voice saying "Hmm. That's funny. . ."

Well, the book has much more where all this comes from. It's short, which tempts a person to read through it quickly. I did, and found that this slighted some of the points it tries to make. It improved on a second pass, in my case, so you may want to keep this in mind.

Comments (17) + TrackBacks (0) | Category: Book Recommendations | Who Discovers and Why

April 26, 2013

The Portable Chemist's Consultant

Email This Entry

Posted by Derek

I wanted to mention a project of Prof. Phil Baran of Scripps and his co-authors, Yoshihiro Ishihara and Ana Montero. It's called the Portable Chemist's Consultant, and it's available for iPads here. And here's a web-based look at its features. Baran was good enough to send me an evaluation copy, so I've had a chance to look through it in detail.

It's clearly based on his course in heterocyclic chemistry, and the chapters on pyridines and other heterocycles read like very well-thought-out review articles. But they also take advantage of the iPad's interface, in that specific transformations are shown in detail (with color and animation), and each of these can be expanded to a wider presentation and a thorough list of references (which are linked in their turn). The "Consumer Reports" style tables of recommended synthetic methods at the end of each section seem very useful, too, although they might need some notation for how much experimental support there is for each combination. For an overview of these topics, though, I doubt if anyone could do this better; I became a more literate heterocyclic chemist just by flipping through things. (Here's a video clip of some of these features in action).

So, do I have any reservations? A few. One of the bigger ones (which I'm told that Baran and his team are addressing) might sound trivial: I'm not sure about the title. As it stands, "The Portable Heterocyclic Chemistry Consultant" would be a much more accurate one, because there are large swaths of chemistry that fall within its current subtitle ("A Survival Guide for Discovery, Process, and Radiolabeling") which are not even touched on. For example, scale-up chemistry is mentioned on the cover, but in the current version of the book I didn't really see anything that was of particular relevance to actual scale-up work (things like the feasibility of solvent switching, heat transfer effects and reaction thermodynamics, run-to-run variability and potential purification methods, reagent sourcing, etc.) For medicinal chemists, I can say that the focus is completely on just the synthetic organic end of things; there's nothing on the behavior of any of the heterocyclic systems in vivo (pharmacokinetic trends, routes of metabolism, known toxicity problems, and so on). There's also nothing on spectral characterization, or any analytical chemistry of any sort, and I found no mention of radiolabeling (although I'd be glad to be corrected on that).

So for these reasons, it's a very academic work, but a very good one of its type. And Prof. Baran tells me that it's being revised constantly (at no charge to previous purchasers), and that these sorts of topics are in the works for later versions. If this book is indeed one of those gifts that keeps on giving, then it's a bargain as it stands, but (at the same time) I think that potential buyers should be aware of what they're getting in the current version.

My second reservation is technological. The book is only available on the iPad, and I'm not completely sure that this is a good idea. There's no way that it could be as useful in print, but a web-based interface would still be fine. (Managing ownership and sales is a lot easier in Apple's ecosystem, to be sure). And I'm not sure how many organic chemists own iPads yet. Baran himself seemed a bit surprised when he found out that I don't own one myself (I borrowed a colleague's to have a look). The most common reaction I've had when I tell people about the "PCC" is to say that they don't own an iPad, either, and to ask if there's any other way they can read it. Another problem is that the people that do have iPads certainly don't take them to the lab bench, which is where a work like this would be most useful. On the other hand, plain old computers are ubiquitous at the bench, thanks to electronic lab notebooks and the like.

All this said, though, if you do own an iPad and need to know about heterocyclic chemistry, you should have a look at this work immediately. If not, well, it's well worth keeping an eye on - these are early days.

Comments (15) + TrackBacks (0) | Category: Book Recommendations | Chemical News

April 24, 2013

A New Book on Longevity Research

Email This Entry

Posted by Derek

The University of Chicago Press has sent along a copy of a new book by DePaul professor Ted Anton, The Longevity Seekers. It's a history of the last thirty years or so of advances in understanding the biochemical pathways of aging. As you'd imagine, much of it focuses on sirtuins, but many other discoveries get put into context as well. There are also thoughts on what this whole story tells us about medical research, the uses of model animal systems, about the public's reaction to new discoveries, and what would happen if (or when) someone actually succeeds in lengthening human lifespan. (That last part is an under-thought topic among people doing research in the field, in my experience, at least in print).

Readers will be interested to note that Anton uses posts and comments on this blog as source material in some places, when he talks about the reaction in the scientific community to various twists and turns in the story. (You'll be relieved to hear that he's also directly interviewed almost all the major players in the field, as well!) If you're looking for a guide to how the longevity field got to where it is today and how everything fits together so far, this should get you up to speed.

Comments (17) + TrackBacks (0) | Category: Aging and Lifespan | Book Recommendations

March 29, 2013

Two New Books

Email This Entry

Posted by Derek

A colleague pointed out to me this week that there's a new edition of Copeland's Evaluation of Enzyme Inhibitors in Drug Discovery. I haven't seen this expanded and updated version, but the previous one was excellent. From the new preface:

. . .I have attempted to improve upon the first edition by substantially expanding most of the chapters with two overarching aims: to cover more completely the experimental aspects of the evaluation methods contained in each chapter and to enhance the clarity of the presentation, especially for the newcomer to applied enzymology. Toward these ends, a number of additional appendices have been added to the text, providing ready sources of useful information as they apply to quantitative biochemistry in drug discovery.

There are also two new chapters - one on residence time as a factor in enzyme inhibitor action, and another on the connections between in vitro enzymology and the factors in vivo that have to be considered for drug candidate selection. I have no problem recommending this one just on this basis.

And on a different (but still very useful) level, Erland Stevens of Davidson College has sent along a new textbook on medicinal chemistry that he's written for the advanced undergraduate/grad student market. I've looked it over, and it's a fine intro to the field, covering an impressively wide range of topics. All the classic stuff is there, but you'll also find references up to at least 2010, including things like George Whitesides' paper on linkers in fragment-based drug design, the structure of the P2X4 ion channel, and screening of crystallization conditions for API synthesis. If I were teaching a survey course on medicinal chemistry, I would be glad to use this as a text.

Comments (2) + TrackBacks (0) | Category: Book Recommendations

January 7, 2013


Email This Entry

Posted by Derek

A couple of years ago, I referred to a journal article summarizing many recent examples of bioisosteres in medicinal chemistry. I've been meaning to mention a book that came out late last year, Bioisosteres in Medicinal Chemistry. It looks to be a compendium of all the latest information on functional group substitutions and their effects on solubility, pharmacokinetics, metabolism and the like. Worth a look if this is one of your interests - you can look over the table of contents at that Amazon link.

Comments (8) + TrackBacks (0) | Category: Book Recommendations

November 30, 2012

Science Gifts: Actual Med-Chem Books

Email This Entry

Posted by Derek

A few years ago, I asked the readership for the best books on the practice of medicinal chemistry and drug discovery itself. These may not be exactly stocking stuffers, at least not for most people, but I wanted to mention these again, and to solicit nominations for more recent titles to add to the list. So, here's what I have at the moment:

For general medicinal chemistry, you have Bob Rydzewski's Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research. Many votes also were cast for Camille Wermuth's The Practice of Medicinal Chemistry. For getting up to speed, several readers recommend Graham Patrick's An Introduction to Medicinal Chemistry. And an older text that has some fans is Richard Silverman's The Organic Chemistry of Drug Design and Drug Action.

Process chemistry is its own world with its own issues. Recommended texts here are Practical Process Research & Development by Neal Anderson and Process Development: Fine Chemicals from Grams to Kilograms by Stan Lee (no, not that Stan Lee) and Graham Robinson.

Case histories of successful past projects are found in Drugs: From Discovery to Approval by Rick Ng and also in Walter Sneader's Drug Discovery: A History.

Another book that focuses on a particular (important) area of drug discovery is Robert Copeland's Evaluation of Enzyme Inhibitors in Drug Discovery.

For chemists who want to brush up on their biology, readers recommend Terrence Kenakin's A Pharmacology Primer, Third Edition: Theory, Application and Methods and Molecular Biology in Medicinal Chemistry by Nogrady and Weaver.

Overall, one of the most highly recommended books across the board comes from the PK end of things: Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization by Kerns and Di. For getting up to speed in this area, there's Pharmacokinetics Made Easy by Donald Birkett.

In a related field, the standard desk reference for toxicology seems to be Casarett & Doull's Toxicology: The Basic Science of Poisons. Since all of us make a fair number of poisons (as we eventually discover), it's worth a look.

As mentioned, titles to add to the list are welcome - I'll watch the comments for ideas!

Comments (13) + TrackBacks (0) | Category: Book Recommendations | Science Gifts

November 17, 2011

Brain Cells: Different From Each Other, But Similar to Something Else?

Email This Entry

Posted by Derek

Just how different is one brain cell from another? I mean, every cell in our body has the same genome, so the differences in type (various neurons, glial cells) must be due to expression during development. And the differences between individual members of a class must be all due to local environment and growth - right?

Maybe not. I wasn't aware of this myself, but there's a growing body of evidence that suggests that neurons might actually differ more at the genomic level than you'd imagine. A lot of this work has come from the McConnell lab at the Salk Institute, where they've been showing that mouse precursor cells can develop into neurons with various chromosomal changes along the way. And instead of a defect (or an experimental artifact), he's hypothesized that this is a normal feature that helps to form the huge neuronal diversity seen in brain tissue.

His latest work used induced pluripotent cells transformed into neurons. Taking these cells from two different people, he found that the resulting neurons had highly variable sequences, with all sorts of insertions, deletions, and transpositions. (The precursor cells had some, too, but different ones, suggesting that the neural cell changes happened along the way). And this recent paper suggests that neurons have an unusual number of transposons in their DNA, which fits right in with McConnell's results.

The implication is that human brains are mosaics of mosaics, at the cell and sequence levels. And that immediately makes you wonder if these processes are involved in disease states (hard to imagine how they wouldn't be). The problem is, it's not too easy to get ahold of well-matched and well-controlled human brain tissue samples to check these ideas. But that's the obvious next step - take several similar-looking neurons and sequence them all the way. Obvious, but very difficult: single-cell sequencing is not so easy, to start with, and how exactly do you grab those single neurons out of the tangle of nerve tissue to sequence them? Someone's going to do this, but it's going to be a chore. (Note: McConnell's group was able to do the pluripotent-cell-derived stuff a bit more easily, since those come out clonal and give you more to work with).

Now, the idea that neurons are taking advantage of chromosomal instability to this degree is a little unnerving. That's because when you think of chromosomal instability, you think of cancer cells (See also the link in that last paragraph. It's interesting, as an aside, to see that those last two are to posts from this blog in 2002 - next year will mark ten years of this stuff! And I also enjoy seeing my remark from back then about "With headlines like this, I can't think why I'm not pulling in thousands of hits a day", since these days I'm running close to 20K/day as it is).

So, on some level, are our brains akin to tumor tissue? You really wonder why brain cancer isn't more common than it is, if these theories are correct. There may well be ways to get "controlled chromosomal instability", though, as opposed to the wild-and-woolly kind, but even the controlled kind is a bit scary. And all this makes me think of a passage from an old science fiction story by James Blish, "This Earth of Hours". The Earthmen have encountered a bizarre civilization that seems to involve many of the star systems toward the interior of the galaxy, and a captured human has informed them that these aliens apparently have no brains per se:

"No brains," the man from the Assam Dragon insisted. "Just lots of ganglia. I gather that's the way all of the races of the Central Empire are organized, regardless of other physical differences. That's what they mean when they say we're all sick - hadn't you realized that?"

"No," 12-Upjohn said in slowly dawning horror. "You had better spell it out."

"Why, they say that's why we get cancer. They say that the brain is the ultimate source of all tumors, and is itself a tumor. They call it 'hostile symbiosis.' "


"In the long run. Races that develop them kill themselves off. Something to do with solar radiation; animals on planets of Population II stars develop them, Population I planets don't."

The things you pick up reading 1950s science fiction. Blish, by the way, was an odd sort. He had a biology degree, and a liking for James Joyce, Oswald Spengler, and Richard Strauss. All of these things worked their ways into his stories, which were often much better and more complex than they strictly needed to be. Here's a PDF of "This Earth of Hours", if you're interested - it's not a perfect transcription, though; you'll have to take my word for it that the original has no grammatical errors. It's a good illustration of Blish's style - what appears at first to be a pulpy space-war story turns out to have a lot of odd background dropped into it, along with speculations like the above. And for someone who didn't always write a lot of descriptive prose, preferring to let philosophical points drive his plots, I find Blish's stories strangely vivid, particularly the relatively actionless ones like "Beep" or "Common Time". He's pretty thoroughly out of print these days, but you can find the paperbacks used, and in many cases as e-books. Now if you're looking for someone who always lets philosophical points drive his stores, then you'll be wanting some Borges. (As it happens, I've had occasion to discuss that particular translation with an Argentine co-worker. But this is not a literary blog, not for the most part, so I'll stop there!)

Comments (30) + TrackBacks (0) | Category: Biological News | Book Recommendations | Cancer | The Central Nervous System

October 18, 2011

A New Book on Chemical Patents

Email This Entry

Posted by Derek

I wanted to mention a book I've received a review copy of recently: Writing Chemistry Patents and Intellectual Property: A Practical Guide. The description is accurate. It'll be most useful for people who don't have access to a lot of well-paid legal talent - or at least would like to get things into shape as much as possible before calling them in and starting the meter running. It goes into detail on what makes a valid application, what patent examiners are trained to look for, and how to draft an application that will stand the best chance of surviving scrutiny. It's not a replacement for a patent attorney - you're still going to need one - but it can keep you from wasting the time of one, or from spending your own money while doing so.

Note added for legal reasons: that's an Amazon affiliate link, meaning that Amazon will (without raising the price to you) rebate a small amount of each purchase you make to me - not just that book, but whatever else you might purchase at the same time. I promise to spend it on the sorts of riotous living that one can fund only through Amazon gift cards.

Comments (4) + TrackBacks (0) | Category: Book Recommendations | Patents and IP

July 26, 2011

Data Handling in Collaborations

Email This Entry

Posted by Derek

I wanted to mention a book I've received, courtesy of the editors: Collaborative Computational Technologies for Biomedical Research. It's a multi-author look at various ways to handle data in all sorts of research partnerships - precompetitive consortia, academia-industrial collaborations, open-source discovery, and so on. Several levels of information are dealt with - patentable IP, raw data, notebook-sharing, etc.

Different readers will find different chapters of use - there's a lot of material covered here, with some unavoidable overlap - but anyone who's having to deal with these issues should definitely have a look.

Obligatory semi-regular note: that's an Amazon link, and this blog is an Amazon affiliate. Any purchases will send a small fee my way, which comes out of Amazon's hide, not yours.

Comments (5) + TrackBacks (0) | Category: Book Recommendations

July 13, 2011

Book Review: The Quest for the Cure

Email This Entry

Posted by Derek

I wanted to mention that I have a review up at Cell for a new book by Brent Stockwell (at Columbia): The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines. I found it a good summary of recent drug discovery, and a look at the attempts to attack "undruggable" targets like protein-protein interaction, transcription factors, and so on. It's written for an educated general readership, and one of the things I wondered about was how books like this find an audience.

Comments (45) + TrackBacks (0) | Category: Book Recommendations

June 8, 2011

Garage Biotech: The Book

Email This Entry

Posted by Derek

I haven't read it yet, but there's a new book on the whole "garage biotech" field, which I've blogged about hereand here. Biopunk looks to be a survey of the whole movement; I hope to go through it shortly.

I'm still on the "let a thousand flowers bloom" side of this issue, myself, but it's certainly not without its worries. But this is the world we've got - where these things are possible, and getting more possible all the time - and we're going to have to make the best of it. Trying to stuff it back down will, I think, only increase the proportion of harmful lunatics who try it.

By the way, since that's an Amazon link, I should note that I do get a cut from them whenever someone buys through a link on the site, and not just from the particular item ordered. I've never had a tip jar on the site, and I never plan to, but the Amazon affiliate program does provide some useful book-buying money around here at no cost to the readership.

Comments (10) + TrackBacks (0) | Category: Biological News | Book Recommendations

October 12, 2010

Drug Discovery History

Email This Entry

Posted by Derek

One of the speakers here yesterday recommended Walter Sneader's Drug Discovery: A History, which I haven't read. It looks good, though, for a look back on how we got here. He also showed some drug structure "family trees" from Sneader's earlier book, Drug Prototypes and Their Exploitation. I haven't seen a copy of that one in quite a while, and no wonder: the only copy shown on Amazon is used, for $500. Sheesh.

Comments (16) + TrackBacks (0) | Category: Book Recommendations | Drug Industry History

September 24, 2010

Serendipity in Medicine

Email This Entry

Posted by Derek

I came across this book the other day, and bought it on sight: Happy Accidents: Serendipity in Modern Medical Breakthroughs. From what I've read of it so far, it's a fine one-stop-reference for all sorts of medical discoveries where fortune favored the prepared mind (as Pasteur put it). There are drug discovery tales, surgical procedures, medical devices, and more.

Even the stories I thought I knew well turn out to have more details. Albert Hoffman's famous discovery of LSD, for example - what I hadn't known was that some of his colleagues didn't believe him when he said he'd taken only 0.25mg of a compound and hallucinated violently for hours. (From what we now know, that was actually a heck of a dose!) So Ernst Rothlin, Sandoz's head of pharmacology, and two others tried it themselves. "Rothlin believed it then", Hoffman noted. Those days will never come again!

Comments (9) + TrackBacks (0) | Category: Book Recommendations | Drug Industry History

May 21, 2010

Friday Book Recommendation

Email This Entry

Posted by Derek

I'm going to be off helping out with my daughter's field trip today, so it's not like there are going to be a lot of posts around here. But I did want to mention this book, "The Elements", by Theodore Gray.

That's this guy, Theodore Gray of Wolfram Research and of Wooden Periodic Table fame. He's clearly a wild man for chemical elements, and good for him. Now what someone needs to do is a coffee-table book on photogenic chemical compounds - dissolving potassium permanganate, crystals of chromium (III) chloride, hunks of copper (II) sulfate. It would (as those examples suggest) be mostly inorganic chemistry, but what the hey. . .

Comments (25) + TrackBacks (0) | Category: Book Recommendations

March 5, 2010

Friday Book Recommendation

Email This Entry

Posted by Derek

Here's another outside the field - in fact, it's outside of a lot of people's fields. Where Is Everybody? presents fifty possible solutions to the Fermi Paradox: if there are a lot of planets in the galaxy, and if life is pretty easy to get going, and if it's possible to travel or just communicate between solar systems. . .why haven't we seen anything? Enrico Fermi, in his typically disconcerting way, ran the math on this question during a lunchtime conversation in 1950, and realized that at least one of the common assumptions behind it must be off, and by a great deal.

I was thinking about this last night, because this weekend I'll have swarms of fourth graders and their parents looking through my telescope (if the weather cooperates), under the auspices of the Amateur Telescope Makers of Boston. And it's impossible to look at the night sky without wondering what life might exist out there and what form it might take. That Wikipedia article is quite good, but if you find it interesting, this book goes into the question in greater detail. I should note that a new book, The Eerie Silence, has just come out on the same topic, but I haven't seen that one yet.

Comments (27) + TrackBacks (0) | Category: Book Recommendations | Life As We (Don't) Know It

February 26, 2010

A Friday Book Recommendation

Email This Entry

Posted by Derek

This isn't exactly med-chem, but its focus probably overlaps with the interests of a number of readers around here. I recently came across a copy of A Field Guide to Bacteria and enjoyed it very much. I don't think there's another book quite like it available: it describes where you're likely to find different varieties of bacteria (from hot springs to your fridge), how they behave in a natural environment (as opposed to a culture dish) and how to identify them by field marks, if possible. It's not written for microbiologists, but it can provide a different perspective even if you work in the field (since many people that do focus on pathogens - really a very small subset of bacteria, when you get down to it).

I'm already inspired to set up some Winogradsky columns with my kids, perhaps with some unusual chemical additives to see what happens. If we discover anything, I'll report back. . .

Comments (11) + TrackBacks (0) | Category: Book Recommendations | General Scientific News | Infectious Diseases

January 15, 2010

Physics, for Dogs and Others

Email This Entry

Posted by Derek

Allow me to recommend a book I received a copy of recently, Chad Orzel's How to Teach Physics to Your Dog. Chad's a fellow scientific blogger from way back, and I have had a chance to consume chicken wings and trade lab stories with him. His new book is a fine addition to the what-the-heck-is-quantum-mechanics field, with some very good analogies and explanations. The format is conversational (which has a long history in the teaching of science), but this time, Orzel's dog is holding up the other end of the dialog. It's a device that lets him get at some pretty complex subjects - complex even for humans, I mean. (The famous Gary Larson "Far Side" cartoon, about dogs being so cute when they try to comprehend quantum mechanics does come to mind). Definitely worth a look.

Comments (12) + TrackBacks (0) | Category: Blog Housekeeping | Book Recommendations

November 28, 2009

Recommended Books For Medicinal Chemists, Part One

Email This Entry

Posted by Derek

I asked recently for suggestions on the best books on med-chem topics, and a lot of good ideas came in via the comments and e-mail. Going over the list, the most recommended seem to be the following:

For general medicinal chemistry, you have Bob Rydzewski's Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research. Many votes also were cast for Camille Wermuth's The Practice of Medicinal Chemistry. For getting up to speed, several readers recommend Graham Patrick's An Introduction to Medicinal Chemistry. And an older text that has some fans is Richard Silverman's The Organic Chemistry of Drug Design and Drug Action.

Process chemistry is its own world with its own issues. Recommended texts here are Practical Process Research & Development by Neal Anderson and Process Development: Fine Chemicals from Grams to Kilograms by Stan Lee (no, not that Stan Lee) and Graham Robinson.

Case histories of successful past projects are found in Drugs: From Discovery to Approval by Rick Ng and also in Walter Sneader's Drug Discovery: A History.

Another book that focuses on a particular (important) area of drug discovery is Robert Copeland's Evaluation of Enzyme Inhibitors in Drug Discovery.

For chemists who want to brush up on their biology, readers recommend Terrence Kenakin's A Pharmacology Primer, Third Edition: Theory, Application and Methods and Molecular Biology in Medicinal Chemistry by Nogrady and Weaver.

Overall, one of the most highly recommended books across the board comes from the PK end of things: Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization by Kerns and Di. For getting up to speed in this area, there's Pharmacokinetics Made Easy by Donald Birkett.

In a related field, the standard desk reference for toxicology seems to be Casarett & Doull's Toxicology: The Basic Science of Poisons. Since all of us make a fair number of poisons (as we eventually discover), it's worth a look.

There's a first set - more recommendations will come in a following post (and feel free to nominate more worthy candidates if you have 'em).

Comments (21) + TrackBacks (0) | Category: Book Recommendations | Drug Development | Life in the Drug Labs | Pharmacokinetics | The Scientific Literature | Toxicology

February 18, 2009

Business Books: The Enantiomers

Email This Entry

Posted by Derek

Since I wrote about business books the other day, and not in a complimentary fashion, reader David Shaywitz sent along a note about his piece in Forbes on reading for newly-humbled CEOs.

Included are intriguing titles like The Halo Effect: ... and the Eight Other Business Delusions That Deceive Managers, which is billed as "a tart takedown of fashionable management theories" and vigorously named Hard Facts, Dangerous Half-Truths And Total Nonsense. Worth a look for people who need (or want) to read about management, but don't find themselves with much to work with from the big bestsellers.

Comments (6) + TrackBacks (0) | Category: Book Recommendations | Business and Markets

February 11, 2009

A Med-Chem Book Recommendation

Email This Entry

Posted by Derek

As per the comments to the last post, this book, Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization, looks like a very nice overview of these issues for the practicing medicinal chemist. From what I've seen of it, there's a lot of you-need-to-know-this information for people getting up to speed, and it also looks to have collected a lot of more advanced topics into one convenient place. If this is your thing, give it a look.

Comments (6) + TrackBacks (0) | Category: Book Recommendations | Drug Development | Pharmacokinetics | Toxicology

February 22, 2007

Inspirational Reading?

Email This Entry

Posted by Derek

An undergraduate reader sends along this request:

I was wondering if you had some recommended readings for a second year student, eg books that you have read and made a palpable impression on you when you were my age.

That's a good question, despite the beard-lengthening qualification of "when you were my age". The books that I would recommend aren't the sort that would require course material that a sophomore hasn't had yet, but rather take a wider view. I would recommend Francis Crick's What Mad Pursuit, for one. It's both a memoir of getting into research, and a set of recommendations on how to do it. Crick came from a not-very-promising background, and it's interesting to see how he ended up where he did.

Another author I'd recommend is Freeman Dyson. His essay collections such as Disturbing the Universe and Infinite in All Directions are well-stocked with good writing and good reading on the subject of science and how it's conducted. Dyson is a rare combination: a sensible, grounded visionary.

Another author to seek out is the late Peter Medawar, whose Advice to a Young Scientist is just the sort of thing. Pluto's Republic is also very good. He was a fine writer, whose style occasionally comes close to being too elegant for its own good, but it's nice to read a scientific Nobel prize winner who suffers from such problems.

I've often mentioned Robert Root-Bernstein's Discovering, an odd book about where scientific creativity comes from and whether it can be learned. I think the decision to write the book as a series of conversations between several unconvincing fictional characters comes close to making it unreadable in the normal sense, but the last chapter, summarizing various laws and recommendations for breakthrough discovery, is a wonderful resource.

Those are some of the ones that cover broad scientific topics. There are others that are more narrowly focused, which should be the topic of another post. And I'd also like to do a follow-up on books with no real scientific connection, but which are good additions to one's mental furniture. I have several in mind, but in all of these categories I'd like to throw the question open to the readership as well. I'll try to collect things into some reference posts when the dust eventually clears.

Comments (26) + TrackBacks (0) | Category: Book Recommendations | General Scientific News | Who Discovers and Why