Come to our new home at CENtral Science:

cenblog.org/terra-sigillata

CENtral Science is the blog presence of the weekly ACS magazine, Chemical & Engineering News

Well, as I’ve been alluding to, I’ve decided to leave this state of indie blog purgatory and join CENtral Science, the blog platform of the American Chemical Society’s Chemical and Engineering News.

C&EN is a weekly publication of the American Chemical Society, the world’s largest scientific society that counts 161,000 members across chemistry-related disciplines. Their blog, C&ENtral Science was retooled last March to establish seven blogs written by several C&EN editors and staff writers.

The CENtral Science blogs and their descriptions are as follows:

Cleantech Chemistry by Melody Voith with Alex Tullo

The Cleantech Chemistry blog will take a close look at the business and technology strategies of a number of companies – many of them new – that hope to serve the world’s need for renewable energy, sustainable agriculture, clean water, and non-polluting manufacturing and transportation, among other cleantech sectors.

Just Another Electron Pusher by Leigh Krietsch Boerner

Just Another Electron Pusher will keep you informed about non-traditional careers in chemistry. Here we talk to people who’ve pursued professions away from the bench about what they do and how they got there. We’ll also follow our blogging heroine in her quest for a satisfying job that uses her degree, but doesn’t involve running any %$@& columns.

Newscripts by Lauren Wolf, Bethany Halford, and Rachel Pepling

“Newscripts” is the companion blog to the like-named weekly C&EN column. Here you’ll find even more quirky news nuggets plus videos, polls, and photo galleries.

The Chemical Notebook by Alex Tullo with Melody Voith

The name directly encapsulates what the blog is meant to be. The topic is the chemical industry: those companies such as Dow, ExxonMobil, BASF, and DuPont that are engaged in the chemical transformation of one molecule to another as of part of a manufacturing stream that ultimately results in products suitable for daily use. By “notebook” what is meant is a reporter’s notebook. The blog aims to make use of those interesting tidbits of the sort found in a reporter’s notebook but might not fit neatly in the print edition of C&EN for one reason or another.

The Editors’ Blog by Rudy M. Baum and A. Maureen Vorhi

There’s nothing cute about the name of this blog or its contents. The only thing to note about the title is that “Editors” is plural, as both Rudy M. Baum, C&EN editor-in-chief, and A. Maureen Rouhi, C&EN deputy editor-in-chief, will host it.

The content you can always expect to find here is the current week’s editorial. We hope readers will use the Editors’ Blog to add their own point of view on the topic being discussed in the editorial. We’ll do our best to respond to comments as they come in. Occasionally, we’ll post an additional entry during the week when something of interest comes to our attention.

The Haystack by Lisa Jarvis and Carmen Drahl

C&EN editors Lisa Jarvis and Carmen Drahl weed through pharma’s molecular mountain to pluck out the drug developments worth noting. Coverage spans science and business context for drug industry news; spotlights on academic and industry conferences; interview outtakes and updates from drug discovery features in C&EN’s pages; and the employment prospects for chemists working in life sciences.

The Safety Zone by Jyllian Kemsley and Jeff Johnson

The Safety Zone covers chemical safety issues in academic and industrial research labs and in manufacturing. The blog is a place for exchange and discussion of lab and plant safety and accident information without the fanfare of a news article. The lead writers are C&EN associate editor Jyllian Kemsley and senior correspondent Jeff Johnson. The blog also includes contributions from other C&EN staff writers as well as health and safety experts in academia, corporations, and government.

I’m delighted to join this fantastic group of writers and will focus on the chemistry aspects of natural products – from prescription and OTC drugs to herbal and non-botanical supplements.

My initial welcome post at the CENtral Science home of Terra Sigillata provides the backstory on my move to my chemistry roots.

I apologize for moving again about a month after leaving ScienceBlogs but I’m grateful that you chose to follow me here. I hope that you’ll join me over at CENtral Science.

These are interesting times. The diaspora from ScienceBlogs and mergers with indie bloggers has brought together new partnerships, such as Scientopia, and strengthened existing ones, such as Lab Spaces.

To help you keep track of these networks, Dave Munger, Anton Zuiker, and Bora Zivokvic launched this week an aggregator of science blogging networks called – no surprise – scienceblogging.org. Many thanks to these fine North Carolina gents for including CENtral Science among their featured networks.

The discerning science connoisseur have more and more choices out there and we appreciate your readership. The next time your leisure reading calls for a science blog, I hope that you’ll consider joining us at CENtral Science, the new home of Terra Sigillata.

Update your bookmarks and RSS feeds

Come to our new home at CENtral Science:

cenblog.org/terra-sigillata

Folks may not know this but ACS is the largest professional scientific society in the world with 161,000 members.

DrugMonkey, the king of science blogging schwag, has previously mentioned the benefits of such a promotion several times to another science blogging network but it never got traction with the powers-that-be.  But here’s the idea from CENtral Science – from this post:

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Here’s how to win:

• Six key words will be hidden among the blogs between August 15–22
• Collect all six key words and bring them to the C&EN booth #527
• Pick up your FREE CENtral Science t-shirt*
• Wear your t-shirt in the exposition hall Monday and Tuesday and you might be selected by C&EN staff to receive one of the VISA gift cards (worth up to $50) given out every half hour

*While supplies last

CONTEST RULES: This promotion is ONLY valid from 8/15 to 8/24. A total of 350 t-shirts will be given out (one per person) from 9:00 a.m. through 5:00 p.m. on 8/23 and 8/24 at booth #527 in the expo hall only. To receive a t-shirt each individual must present all 6 (correct) key words. Winners must be ACS members to participate. ACS staff and their families are not eligible. All gift card recipients must be wearing a CENtral Science t-shirt. There is no guarantee of winning any prize. Gift card winners will be chosen at random every half hour during published expo times.

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Now THAT’s how you do it.

You have to read the blogs to pick up each of the six keywords.

Three hundred and fifty T-shirts. 350!

And you wear them at the meeting.

And they give away a $50 $10, $25, or $50 gift cards every half hour for two days.

The T-shirt is very nice, by the way, and I’m grateful to C&EN Online editor, Rachel Pepling (Twitter) for sending me one. I will be wearing it for our panel discussion on Tuesday! Rachel’s also a Gator so she gets even more favor points from me.

Once again, hunt me down in Boston if you’d like to say hello.  I’ll be the one in the yellow CENtral Science T-shirt.

Blogging has been and will be light over the next few days while we are packing up things around here to move to our next, more permanent home.

In the meantime, you may have noticed here and on Twitter that part of my big news is that I will begin writing under my PharmMom-given name.

My dilemma has been that I have two Twitter accounts. @AbelPharmboy has been the one I use for all blog-related stuff as well as any other gems of my mind that can fit into 140 characters.  Thanks to you, I have 1,600 followers at that account. However, I also have a real name Twitter account that I used for my now-fledgling-and-almost-nonexistent music career and local banter with folks in the Durham-Chapel Hill area. That one only had 200 followers until I began announcing my metamorphosis.

With the pending blog move and melding of my IRL and online identities, one of my mentors, Twitter follower, writer, editor, and Johns Hopkins journalism professor, Mary Knudson, asked what I was going to do regarding the two avatars I use for each Twitter account.

One of my dear friends was enthusiastic about me coming up with a new avatar for the real name account but I’ve been worried about losing old followers who might not recognize the real name avatar.

But coming to the rescue from across the pond is my devoted reader and neuropharmacology enthusiast, Synchronium – world-famous for showing not one but both nipples in the British press.

Here is my metamorphosis:

Follow me now @davidkroll on Twitter.

More news on our move as it becomes available.

I'll get to meet one of my heroes. Image courtesy of Pharmagossip.

I’m really excited to be going up to Boston for a few days next week to attend the fall meeting of the American Chemical Society.

Besides presenting some of our collaborative work, the highlight of my time there will be with Carmen Drahl of C&EN and The Haystack blog hosting a panel on chemistry and pharmaceutical blogging. The session will be held 12 noon – 2 pm on Tuesday, August 24 with Derek Lowe (In the Pipeline), Ed Silverman (Pharmalot), Michael Tarselli at Scripps Florida, and your humble correspondent.

Here’s a PDF with more details. Fellow Haystack blogger and C&EN Senior Editor, Lisa Jarvis, will be livetweeting the session. So be sure to follow Lisa @lisamjarvis.

Here’s the description from Carmen:

These folks will each give a short talk, but the real highlight here is the panel. I’d love for people to show up with great questions. Want to talk about how blogs are playing a role in discussing layoffs and employment? How about the trickiness to promoting new drugs on the web? Or what role new media should have in critiquing papers? The panel’s as good a time as any to bring those issues up.

I’ll be moderating the event, which is slated for Tuesday, August 24, from 12 noon till 2PM in the Boston Convention Center, Ballroom West.

It costs $16 to sign up for the session, which includes lunch. You can register for the event at the main ACS meeting registration site here. It is listed as the MEDI Lunch and Learn/Ticket No. SE 19.

Get more information about the event from this promo flyer.

I’ll be honest with you folks – I’m peeing my pants with anticipation.

Derek Lowe is the grand master of pharma blogging. Derek is a medicinal chemist who has somehow managed to write from the standpoint of a pharmaceutical industrial chemist and give us insights that you’ll rarely find elsewhere in the blogosphere. In fact, it was an interview with Derek in The Scientist in August 2005 that led me to start this blog. Derek does us a great service in academia by helping our trainees learn what it’s like to work inside a drug company, a place that about half of my trainees and fellow Ph.D. students now work. The 52 posts in his “Academia vs. Industry” category is a great place to start reading.

Ed Silverman is the go-to writer for coverage of the pharmaceutical industry, at least on this side of the pond (hello, Pharmagossip!). I respect a lot of other pro writers and bloggers on that beat such as Matthew Herper at Forbes and Scott Hensley when he was at the Wall Street Journal Health Blog, but now editor of NPR’s Shots health blog.

But Ed wrote for many years at the newspaper of my childhood, the Newark Star-Ledger, at a time when I dreamed of working for a northern New Jersey pharmaceutical company. With 75% of US pharmaceutical companies having a presence within 150 miles of Newark, Ed was at the heart of the business and told it like it is.  In the new home of Pharmalot with Canon Communications, he continues to provide cutting edge news on the drug industry and current legal actions in the community. Ed’s off on summer break right now but will return in time for our talks and panel discussions.

I haven’t met Michael Tarselli yet but I’m excited to do so and learn about the Scripps presence in Jupiter, Florida, where I have a few old colleagues. I’ve already been fortunate to meet Carmen, a Princeton-trained PhD chemist-turned journalist – Bora Zivkovic has a nice interview with her from ScienceOnline2010.

For those of you who won’t be there, Carmen is asking folks to send in questions for the panel via this survey form.

I want to ask Derek how in the heck he got the okay to blog from the highly risk-averse environment of a pharmaceutical company and how he approached this when a plant closure required that he find another position. Did his blogging help him drum up prospects and did his ultimate employer view his visibility as a blogger as a plus?

And in the wake of the Pepsigate exodus from ScienceBlogs, what is the place for writing about being a scientist in industry without being a pawn of one’s employer? I think that it’s essential for there to be just as much blogging by industry scientists as by academics and professional science writers. In chemistry, it seems to be much more accepted that one will work in a corporation (my data-free impression only). But our fellow scientists trained in pharmacology, genetics, or molecular biology have just as much opportunity to work in industry, large and small. Why aren’t we doing more in the blogosphere to prepare our trainees for these opportunities?

What would you like to see discussed at this panel? Drop a line in the comments or go over to Carmen’s response page.

And if you’re in Boston, please come say hello!

This weekend, I saw a Lake Charles, Louisiana story from KPLC-TV coincident with the statewide ban on synthetic marijuana products that took effect on August 15th following legislation signed by Gov. Bobby Jindal in June. One convenience store owner remarked on how the ban will affect her business:

Patricia Maynard, co-owner of Westlake’s Quick Stop, said selling the herbal substances has allowed her to stay in business and keep her electricity on.

Now, that the state has banned synthetic cannabinoid, Maynard is worried her business will suffer. [APB: should be "cannabimimetic" not "cannabinoid" because the active compounds differ structurally from cannabinoids]

“Look how much revenue the state’s going to lose,” said Maynard. “I really don’t understand it. I really don’t understand their reasoning behind it and yeah, it’s definitely going to hurt my business.”

But the final sentence is what caught my eye:

Synthetic cannabinoid is still legal if prescribed by a doctor as a homeopathic drug.

Today’s our first day of classes so it’ll take me some time to dig into the laws governing homeopathics in Louisiana. Technically, a K2 or Spice product cannot possibly a homeopathic remedy because it actually contains measurable amounts of active components. I wonder how long it will take K2 manufacturers to take advantage of this loophole and how much  homeopathic “physicians” might charge “patients” for such a referral.

Click here to read my compilation of synthetic marijuana posts at the new home of this blog.
 

From the overnight e-mail referrals of PharmGirl, MD, whose insomnia fuels much of my blogging, comes a story from Middletown, Indiana, on the death of a 28-year-old woman from smoking a synthetic marijuana product.

From WXIN-TV in Indianapolis:

A mother of two is dead after using a synthetic-marijuana laced incense known as “Spice.”

Now her friends and family want the drug outlawed since more and more people appear to be dying from it.

“Yesterday I lost one of the most important people in my life,” says Heather Hogan, blinking back tears, still trying to make sense of a life taken so suddenly.

A common brand of "herbal incense" or "synthetic marijuana."

Several “herbal incense” products sold as K2 or Spice (usually Spice Gold) have permeated the media over the last year, in the US at least, as legal alternatives to marijuana. These products contain one or more synthetic chemicals designed to bind the same cannabinoid receptors in the brain as those affected by the active compounds in marijuana.  These synthetic compounds, called cannabimimetics, do not have the same chemical structure as marijuana’s THC but still have equal or greater potency and effectiveness. Most recognized among these chemicals is JWH-018, so named by the research team of Clemson University professor emeritus, John W. Huffman, who worked on these molecules as biological probes in the mid-1990s together with some of the best behavioral pharmacologists in the US.

For more reading, go to these posts by us, DrugMonkey, and Dr. Leigh.

However, if these compounds do indeed behave like those in marijuana, deaths associated with their use might not be expected.  However, there is at least one other Indiana death from May that is associated with Spice use. Unlike the current article, the May case has a statement from the coroner:

“Given that it was reported that the decedent may have used an unknown substance call “K 12 spice”, a synthetic drug being used by some smokers as a legal substitute to marijuana, we will review the toxicology results to determine what chemicals are involved. We know that there are current studies being done to determine the effects of this substance. We will follow this case closely and watch for other related types of unexpected deaths.”

The coroner probably meant K2, not K12. But regardless, could this stuff cause death?

DrugMonkey, Leigh, and I have been monitoring the literature and our comment threads but most of what we see are from users who report, at worst, some very unpleasant experiences with K2 or Spice use.  However, a couple of our commenters have noted that the products can cause seizures. And if severe enough, a seizure can cause death. (P.S. Leigh has started writing a new blog at Scientopia.org called Neurodynamics.)

This particular commenter of ours who purchased pure JWH-018 to make his own herbal blend reports that while one cannot usually overdose on marijuana, high doses of this compound are very different. Other habitual marijuana users report that some high-dose effects of K2 Spice reported sound similar to those of very strong strains of cannabis.

More and more of these kinds of products are popping up under other names such as Colorado Chronic, Dragon Spice, HUSH, and others.

So, what’s the story here? Let’s assume for a moment that these deaths can be causally linked to synthetic marijuana use.

Could lethal effects of K2 Spice be due to a synthetic contaminant?

My hypothesis is driven by pharmacology/toxicology history. In the early 1980s, young people started showing up in San Francisco hospitals with symptoms of shaking and muscle rigidity that looked just like Parkinson’s disease that usually afflicts folks in the 60s or, in the early-onset version, their 40s. The cases were traced back to an East Coast chemistry graduate student who had been trying to synthesize MPPP an analog of the synthetic opioid drug, meperidine, to prepare a “synthetic heroin.”

In this 1983 Science paper, J William Langston and other colleagues at Stanford identified the presence and activity of a neurotoxic by-product of illicit MPPP syntheses called MPTP. Langston’s group reviewed that case of the Maryland chemistry graduate student who had presented with similar symptoms in 1976 while using this 1947 synthetic scheme, part of a series of four piperidine synthesis papers in that issue of the Journal of Organic Chemistry. Davis et al. reported on this case in 1979 in Psychiatry Research that the student noted the onset of parkinsonian side effects when injecting the compound made after taking some synthetic shortcuts following several successful batches. The student, now known as Barry Kidston, died after a cocaine overdose and his brain slices are those shown in the Davis paper.

Langston’s group later reported in Neuroscience Letters that MPTP is metabolized in the brain of non-human primates to the highly-reactive neurotoxin, MPP+ (interestingly, an equally high ratio of MPP+ to MPTP was observed in the heart but I’ve not read anything about cardiac effects of MPTP). I should also note that the use of non-human primates for this work was critical to understanding how this toxin caused parkinsonism – the effects were not seen in rats given MPTP.

Production of this highly-reactive pyridinium ion was later shown to result form neuronal metabolism by monoamine oxidase B, the same enzyme we normally use to inactivate dopamine. The MPP+ caused selective death of dopamine neurons in the substantia nigra, “comparable in severity to that usually seen in idiopathic parkinsonism.” (Quote from Langston et al, Science 1983; 219:979-80 about Kidston’s pathology)

For more reading on this topic, Langston co-authored a 1995 book entitled, The Case of the Frozen Addicts, that also fueled a NOVA special. A New England Journal of Medicine review of the book appears here.

MPPP, the intended illicit compound, and MPTP, the proneurotoxin that is oxidized in the brain to MPP+.

This remains an active area of research today because environmental causes of parkinsonism may be mediated similar by compounds we encounter daily – in the 1980s, Sol Snyder’s group at Hopkins showed that MPP+ is made in and exported from astrocytes to kill surrounding neurons and just last year another group at Rochester and Columbia showed that identified an organic cation transport protein, oct3, that’s responsible for this export.

In the case of JWH-018 and related compounds, they are not piperidine (a six-membered saturated ring containing nitrogen) but rather indoles, a five-membered nitrogen-containing ring connected to a benzyl ring. Both are heterocycles, meaning they are carbon rings with nitrogen and, like the methyl on the pyridine nitrogen in MPTP, the nitrogen in JWH-018 is modified with an aliphatic group (a five-carbon pentyl group, in this case).

The cannabimimetic, JWH-018, sold pure and in K2, Spice, and other "synthetic marijuana" or "herbal incense" products.

My question to my chemistry colleagues is whether something could happen in the JWH-018 synthesis to create a situation on the indole that could allow this to be activated to a reactive cation. I’m not sure how the carbonyl electrons one carbon off from the indole might influence things. But then again, we have indoles everywhere endogenously – in tryptophan and serotonin.

Just thinking out loud here – although I’m happy to partner with one of my chemistry colleagues to suss this out – but the cases of deaths reported with K2 Spice, if causally associated, seem too sporadic to be a general theme. The fact that these two cases (and perhaps three) in Indiana smells to me like a locally-restricted distribution of a “bad batch.” I anticipate that poison control centers and forensic analytical chemists in Indiana are on the case.

But here’s a case where I really wish I knew chemistry better. But, in true blog tradition, I’d rather open up this discussion to chemists of the blogosphere rather than try and be all secretive and see if this hypothesis can be quietly tested with my colleagues.

I see that some of my chemist friends have followed me over here from the old digs at ScienceBlogs – what say you, o learned ones?

Today, the Henrietta Lacks Foundation awarded its first ever grants thanks to donations from Rebecca Skloot, and many readers. The first awards cover full tuition and books for five descendants of Henrietta Lacks starting fall semester 2010, as well as an emergency grant for one of Henrietta Lacks’s sons. More information about the inaugural Henrietta Lacks Foundation grants coming soon. For more information on the foundation, or to make a donation, click here.

As some readers know, I have been a big fan of Skloot’s book, The Immortal Life of Henrietta Lacks, and I have been the beneficiary of the cervical carcinoma cell line established in 1951 from the Ms. Lacks’s tumor.

When Rebecca announced last year that she was to establish a foundation to funnel profits and donations to assist the Lacks family, one of her primary goals when embarking on this project more than ten years ago, she also asked me to serve on the board of the Foundation.

I’ll have more to say about this process when a formal press release is made. But for the time being, I consider myself incredibly fortunate to do my part to honor the memory of Henrietta Lacks and assist her descendants.

Some of my colleagues question the merits of the P01 program since some just appear to be a group of individual grants that really don’t function interdependently – I tend to think that good P01s do a great job (disclosure: our lab is part of a collaborative P01 subproject led by a great senior person in my field who is deeply committed to the development of junior scientists).

But back to TGR. In his self-admitted angry rant, he asked:

Seriously to have two grants that old, um has there never been a fucking priority shift? Ever? At some point wouldn’t the NIH cutoff funding for the grant as this dude has probably drug this shit down the road for way to long.

TGR gets clever-points from me simply for the dead, driftwood photo in Figure 1 with the caption: “The overfunded PI with grants almost as old as I am!”

Believe it or not, grants funded under the same project name for more than 30 years are quite common.  In fact, a search of the NIH RePORTER database (the successor to CRISP), reveals this 62-year-old project as the longest I could find. The grant number is 5R01GM000091-62.

NIH grant nomenclature

As an aside, you can dissect this seeming gibberish by noting that the first number denotes the stage of the grant: Most common are Types 1, 2, and 5. Type 1 grants are brand-new, type 2 grants are competing renewal applications that are submitted after the original grant period expires, type 5 grants (like this one) are in the years of a funded grant period where the grant is renewed annually without additional peer-review. Other commonly-used definitions are the type 3 which is the award when an administrative supplement is requested, for example, to fund minority scientists for new studies related to the main thrust of the grant, or the type 7 which denotes a grant that has moved with the principal investigator to a new institution. Less common types I don’t know much about are the type 4 which seems to be a flavor of type 3 grants where additional funds are awarded and the type 9 which is used to describe grants whose primary funding institute has changed.

The two letter code, GM in this case, denotes the primary funding institute, National Institute of General Medical Sciences (NIGMS). Many folks in my field have CA designations for the National Cancer Institute.  My alcohol research colleagues will often have grants from NIAAA denoted AA and substance abuse research colleagues will have DA to denote projects funded by the National Institute for Drug Abuse.

The following six numbers are simply the sequential numbers of the grant that are assigned to each application regardless of whether it is ultimately funded. Yes, this was the 91st grant submitted to the NIGMS.

And, back to this discussion, the 62 denotes the year of the grant. You’ll see some grants where the last two numbers are followed by an A1 or the now-defunct A2, denoting a revised or “amended” application, or a S1 for a type 3 grant supplement. There are other designations that I’m sure other folks will drop in the comments.  Anyway, you can tell a lot about a NIH grant from its number.

Led until 2007 by Duke biochemistry professor emeritus, K.V. Rajagopalan, the most recent version of the grant investigated an unusual molybdenum co-factor, molybdopterin, as the central prosthetic group for almost all molybdenum-containing enzymes. Molybdenum deficiency is an autosomal-recessive trait that cause seizures in infants and invariably leads to childhood death. There is no known treatment. The activity of sulfite oxidase, a Mo-containing enzyme, has been a diagnostic test for the disease used since 1983 and many of the sequelae of the disease seem to be a result of sulfite accumulation and toxicity in neurons. This round-up from the International Molybdenum Association details some of the work on the role of molybdenum in human biology.

Dr. Rajagopalan has been a prolific biochemist with 199 papers on PubMed. Two of his first four papers in 1958 and 1959 were in Nature, and his last two in 2008 and 2010 were in Biochemistry and Journal of the American Chemical Society. One of my learned colleagues mused as to whether Dr. Rajagopalan was the original principal investigator on the grant (since NIH RePORTER doesn’t have records that far back – only to 1987 or 1989 in most cases). However, the first grant would have been awarded in 1945, assuming that grant periods were still one-year in length in those days. Of course, NIGMS wasn’t established until 1962 and the NIH, which traces its history to 1887, wasn’t established in name until the Ransdell Act of 1930 when it was called the National Institute of Health (singular).

So, it is likely that this longstanding grant was originally awarded to another P.I. – perhaps Dr. Rajagopalan’s mentor – in another institute, or perhaps just plain old NIH itself. It’s rather common, even today, for a well-qualified trainee to be named as P.I. of a grant when one’s mentor passes on to The Great Study Section in the Sky. Getting that grant renewed, however, is as tough as getting a brand new grant.

Longtime grantees – Deadwood? Driftwood? Or Clue Stick?

TGR may also care to note that the convention in the old days was to have a very broad grant title with the grant competitively reviewed for renewal on newly designed experiments. Much effort is expended on the merits on long-time renewed grants with young(er) folks like TGR criticizing longtime grantees as “deadwood” while more seasoned investigators note that a renewal means not only proposing new ideas but also being more carefully reviewed for progress on the previous aims of the grant.

For example, one of the fathers of my field – and one of the most encouraging people I have ever met in cancer research – Joe Bertino, had a grant entitled, “Mechanism of Action of Folate Antagonists,” that expired in year 45 only six weeks ago. Bertino was, and is, still doing cutting edge work on a class of drugs represented by methotrexate, whose clinical use he launched with Bruce Chabner and others quite early in his career. Even with a couple of high level administrative positions at the Cancer Institute of New Jersey and the University of Medicine and Dentistry of New Jersey, Bertino led a project on microRNA regulation of dihydrofolate reductase (DHFR) that appeared recently in PLoS ONE. Bertino’s group showed that miR-24, a tumor-suppressor microRNA normally modulates DHFR activity (required for nucleotide biosynthesis and cell proliferation) but a polymorphism in the DHFR 3-UTR prevents miR-24 action leading to high level production of DHFR that contributes to neoplastic transformation. Melding novel concepts of carcinogenesis with a career of work on DHFR is an example of the kind of thing that longtime grant renewals support.

Grant renewals were the norm when I was coming up in the 1980s and my tenure decision in the 1990s was highly dependent on the renewal of my first R01 that came through a few months before the review committee met. I don’t have statistics handy but my anecdotal experience on NIH study sections over the last decade of so have led me to think that grants renewed more than twice are becoming less common.

So rather than view double-digit-year grants as evidence of driftwood or deadwood, I would argue to TGR that such grants are evidence of a long career of investigator productivity together with the sustained ability to compete at the top 10-15 percentile of scientists in the field. Does a grant with a -26 influence a reviewer’s perception, especially a first-time grant reviewer? Perhaps. But in both ways. Some reviewers, especially first-time reviewers, might feel that they might be missing something if the grant appears to be shite while others might simply dismiss the -26 before they even start reviewing as though the grant carries a “Kick Me” sign.

My personal opinion is that most grants with more than 20 years of support have clearly earned it. I can’t argue individual cases whose history I don’t know – especially those outside my field as the example of TGR seems to be. However, my dear weedhopper may care to consider some of these points in his angry rant.

Real deadwood would be faculty who occupy positions without any grant funding who also shirk teaching responsibilities, resist any change or innovation by junior faculty, hold forth with painful, droning, and meaningless diatribes at faculty meetings, and bitch to you about the tough old days (when grants were funded at the 35th or 40th percentile) when they had to synthesize phosphate buffer from the elements..uphill, both ways, in blinding snow and ice.

But, then again, young investigators are supposed to be full of piss and vinegar.

ADDENDUM: Colleagues who have also weighed in:

DrDrA – Blue Lab Coats

JUNIORPROF

I read the Denver Post all the time online but I somehow missed last week’s photo gallery of rare color pictures taken in the US during the Depression and World War II:

These images, by photographers of the Farm Security Administration/Office of War Information, are some of the only color photographs taken of the effects of the Depression on America’s rural and small town populations. The photographs are the property of the Library of Congress and were included in a 2006 exhibit Bound for Glory: America in Color.

The color plates are absolutely breathtaking. The images bring a time alive that many of us only heard of through our grandparents or saw in detached black-and-white photographs. I was not fully prepared for how the color made me think differently about those times and have more empathy for those who lived through those hard times.

Two photographs are particularly noteworthy to me: #54 and #66.

The first shows a group of women railroad workers having lunch in 1943, a time when so many men were off to war that workforce necessity overruled the gender roles that permeated the post-war 1950s and beyond.

The second photo shows an African-American woman installing rivets into an airplane in a scene reminiscent of the motivational “We Can Do It!” war campaign of Rosie the Riveter. Rosie the Riveter was based on a Norman Rockwell painting I had the good fortune of seeing displayed one summer in Aspen, Colorado. Not well-appreciated about the original painting (which appeared on the May 29, 1943 cover of The Saturday Evening Post) is that the stout woman is shown eating her sandwich on a stool with her riveter while resting her foot on a copy of Hitler’s Mein Kampf.

The Wikipedia entry on this campaign is fascinating and, interestingly, features photo #66 as the first in the entry.

I’m not an anthropologist but I find these images striking because they represent a time when societal needs outweighed our feeble penchant for racial and gender discrimination.

Many thanks to Maggie Koerth-Baker at Boing Boing for making us aware of this photo gallery.