How to promote a science blogging network at a national scientific meeting

Bora Zivkovic, DrugMonkey, and I have been really impressed by this idea by the online folks over at the American Chemical Society’s Chemical & Engineering News. This week, their blog network, CENtral Science, has been promoting their presence at the upcoming national ACS meeting in Boston.

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.

Yes, Weedhopper, you can have the “same” R01 for decades

A discussion ensued yesterday among several of my learned colleagues following this post by The Genomic Repairman. Therein, TGR noted that a senior person in their field had two grants in their 27th year and 26th year, respectively. In NIH grant parlance, one is called a R01 (and that’s R-zero-one, chief), an investigator-initiated grant that is the bread-and-butter type of support by which the mettle of most biomedical researchers is evaluated. The other is called a P01, or program project, a group of R01-sized projects with one or more core programs that support each other in what is intended to be synergy.

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

Support for Duke breast cancer colleagues post-Potti

I came home yesterday and looked at the mail with a shudder: the Summer 2010 issue of the biannual Duke Medicine DukeMed magazine greeted me with a cover on personal genomics in breast cancer.

Oh no.

As a twice-yearly publication, it was probably published weeks ago and was sitting in a warehouse ready for mailing. All this while when The Cancer Letter broke the story about credentials issues surrounding Dr. Anil Potti and raised awareness of widespread criticism in the field surrounding work from him and Dr. Joe Nevins on genomic signatures and drug sensitivity of patient tumors (our post with links to reports here).

Indeed, Potti and Nevins were still quoted therein (article text here, full issue 4 MB PDF here):

“Genomics will revolutionize cancer therapy,” says cancer researcher Anil Potti, MD. “It allows us to identify a fingerprint that’s unique to every individual patient’s tumor. If you can match that fingerprint with the drug that’s most likely to work for that patient, you can make cancer treatment more effective and less toxic. It brings us closer to a cure.”

Potti and Joseph Nevins, PhD, of the Duke Institute for Genome Sciences & Policy, have led the effort to look at gene expression profiles from large groups of tumor samples and compare those profiles with treatment outcomes, searching for patterns (or genomic signatures) that indicate the “personality types” of tumors — those that are likely to metastasize or not; those with good prognosis and poor prognosis; a tumor that is resistant to a drug or one that is sensitive to a drug.

But the vast majority of the article featured several other Duke oncology physician-scientists with quotes and profile photographs on other efforts there to personalize breast cancer treatment. Several of these folks are colleagues who I respect deeply and whose scientific ethics and clinical dedication are beyond question – all are tremendous physicians who’ve relieved the suffering of thousands of women with breast cancer (perhaps a couple tens of thousands – and a couple of hundred men with breast cancer as well.)  One I recognize as a heme/onc fellow I taught in an AACR laboratory workshop over 10 years ago.

Just as many of my esteemed colleagues in the pharmaceutical industry are tarred with sweeping generalizations following high-profile but individual cases of unforgivable impropriety, I fear that some of my valued Duke colleagues may be similarly viewed by the broad public.

I recognize that the pending internal and external investigation of the Potti case may reveal some collusion of institutional leadership and culture.

However, I wish to register my personal and professional support for my other Duke colleagues quoted in this issue of DukeMed.

If my mother had a recurrence of her breast cancer or could gain access to an experimental treatment in a clinical trial outside of those based on Potti’s science, I would still send her there in a heartbeat.

Disclosure: I was co-author with one of the named physician-scientists on a 2004 Journal of Clinical Oncology case report of a breast cancer patient who experienced a delayed-hypersensitivity reaction during chemotherapy following injection of a mistletoe extract by a naturopath. Another co-author was my spouse, a former Duke physician-scientist. Since 2001, I’ve also held an adjunct faculty appointment at Duke and am a member of their NCI comprehensive cancer center. I draw no salary or other compensation from these appointments.

Useful and dynamic departmental websites? Anyone? Bueller?

As you begin your week, I was hoping that I might impose upon you for some suggestions or examples from your neck of the woods.
Working with my talented and forward-thinking university Web Services colleague, Damond Nollan, I have the opportunity to craft from scratch a website for an academic department.
I’ve found many examples of good, individual laboratory websites and The Scientist even ran a contest two years ago for such sites.
However, I’ve not seen much attention on what makes a good academic department website, what people want to see in a departmental website, or good examples of such.
I like to see current information on what is going on in the department, general news, seminar programs, recent accomplishments, outreach activities, student and postdoc pages. But I’d also like to know of any sites that might have a chair’s blog, a newsfeed of topical stories in the field, links to social media, engagement of alumni and alumni accomplishments, and other attributes that don’t allow cobwebs to accumulate.
In fact, Jeffrey McClurken at The Chronicle’s ProfHacker blog recently spoke of creating an alternative departmental website that employs many of the dynamic aspects of the blog.
(P.S. You really should be reading ProfHacker if you aren’t – what a fantastic resource written by some of the best-wired profs around the US)
Of course, McClurken notes that some institutions are restrictive on design, graphics, and hosting for any site not under the purview of the university IT department. But his example of the site for the Department of History and American Studies at Mary Washington University is a good example of a site that is regularly updated and has the capacity for easy-updating by people who don’t know how to write code.
So, if you care to blow off a few minutes of your Monday, do you have any ideas on
1) what you look for on a departmental web
2) any good examples thereof
3) any caveats or cautions I have not mentioned?
Keep in mind that this is not limited to the biomedical sciences – I’m looking for common threads to department websites that are most useful for faculty, students, alumni, and staff, as well as prospective students, postdocs, faculty, and staff.

What’s the difference between HeLa and HeLa S3 cells? Part III: Theodore “Ted” Puck, PhD, and the first clonal isolation of human tumor cells

ResearchBlogging.org
This post is the third in a series on the origin and history of HeLa S3 cells. The first post details how I came about to ask this question when launching my independent research laboratory. The second post details the life and careers of the legendary physician-scientist pioneer, Dr. Florence Rena Sabin.
Today, we take up a discussion where we will finally learn the origin of HeLa S3 cells, complete with original literature citations.
A recap
We left our previous discussion with the final and still-productive years of Dr. Florence Rena Sabin. After graduating from Johns Hopkins Medical School in 1900, Dr. Sabin embarked on a nearly 40-year career at Hopkins and now-Rockefeller University, elucidating the developmental origin of the lymphatics and antibody responses to tuberculosis and training a generation of physician-scientists. She was truly a pioneer, becoming the first woman to be appointed to faculty at Johns Hopkins, their first female full professor, the first female full member (full prof-equivalent) at Rockefeller, and the first woman invited to join the National Academy of Sciences.
Upon her retirement in 1938, she returned to her native Colorado to join her sister, Mary. Near the end of World War II, she was tapped by the Colorado governor to lead a committee that would address existing public health issues in the state that would have to be solved while absorbing a large number of men and women returning from the war to civilian life. Although in her 70s, Sabin was highly effective and shared the 1950 Lasker Award for Public Service. In 1951, the University of Colorado School of Medicine honored her with the dedication of the Florence R. Sabin Research Building for Cellular Biology.
That same fall was a sharp contrast for the Virginia-born tobacco farmer, Henrietta Lacks. She, too, was spending time at Johns Hopkins. But in this case, it was because her life was being cut short at age 31 from an aggressive case of cervical cancer.
In the months before her death on October 4, 1951, cells derived from her tumor had been successfully cultured in the Hopkins laboratory of Dr. George Gey. These cells were called HeLa, so named for the first two letters of Henrietta Lacks’s names, and took a place in history as the first human cell line to be continually propagated in culture. They would live on in laboratories not only at Hopkins but around the world, including that of Colorado geneticist, Dr. Theodore “Ted” Puck.
From bacteria and bacteriophage to human genetics
Puck from Rowley obit.jpgTed Puck came to Colorado a few years earlier. His 1994 autobiography in the American Journal of Medical Genetics tells you far more than I can here. Here he shares his situation before the Sabin Building became available:

On my arrival in Denver in 1948, I first became aware of the magnitude of the responsibility which I had undertaken. The total contribution of the medical school to the budget of the Department of Biophysics was $5,000 per year. All the rest was to come from grant funds. I was the only faculty member in the newly formed department which was required to present a major course to the medical students, to institute graduate training leading to the Ph.D. degree in biophysics, to conduct a post-doctoral training program for
M.D.’s and Ph.D’s, to conduct a significant research program in biophysical science, and to raise the necessary grant funds for those activities. An old unused lumber room in the basement of the medical school was cleaned out, painted, and transformed into offices and a laboratory for the department.

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What’s the difference between HeLa and HeLa S3 cells? Part II: The life and careers of Florence Rena Sabin, MD

This post is the second in a series on the origin and history of HeLa S3 cells. The first post can be found here. In this post, we discuss the life and careers (yes, careers) of the remarkable physician-scientist, Florence Rena Sabin.
“Too bad you’re not a boy, you would have made a good doctor.”
Sabin birthplace home Central City Smith College collection.jpgFlorence Rena Sabin was born in the mining town of Central City, Colorado, on November 9, 1871, two years after her sister and lifelong companion, Mary. Florence’s father. George Sabin, had moved from Vermont to Colorado in the midst of the Colorado gold rush and a notable 1859 gold strike between the towns of Central City and Black Hawk. Her mother, Serena (Rena) Miner (yes, Miner), was a Vermont school teacher in Savannah, Georgia who moved sight unseen to Black Hawk to respond to an ad for a schoolteacher. (This photograph of their home, like many in this post, are derived from The Florence R. Sabin Papers, freely available from the National Library of Medicine’s Profiles in Science Collection.)
If you’ve driven I-70 from Denver International Airport to any number of Colorado ski areas, you have passed a highway specifically built to bring you to these two former mining towns for a different kind of gold: limited stakes casino gambling.
Tough, hardscrabble living in the mountains led the family to move to Denver while Mr. Sabin continued to work in the mining business. Sadly, the girls’ mother died in childbirth in 1878 and George Sabin enrolled his daughters in a boarding school called Wolfe Hall, where both would later teach. Mr. Sabin recognized how deeply the girls were devastated by the loss of their mother and his long absences didn’t help matters. The girls were sent to live with their uncle Albert in Chicago – though not the Albert Sabin of poliovirus vaccine fame. He brought them to visit and then ultimately live with their paternal grandparents in Saxtons River, Vermont.
I belabor this issue because it was then that Florence’s grandmother remarked that one of their ancestors, Levi Sabin, had been a doctor and her father had attended medical school for two years before moving to seek his fortune in gold. Observing Florence’s love of nature and biology, her grandmother remarked, “Too bad you’re not a boy, you would have made a good doctor.”
Florence apparently took this statement as a challenge, vowing to become a doctor anyway. She finished school in Vermont and attended Smith College where she was befriended by the school physician, Dr. Grace Preston. Preston took an interest in Florence, cultivating her interest in biology and chemistry and advising her about a new university in Baltimore whose medical school would be accepting women owing in part to an unusual turn of events.
Money talks: how wise women influenced a new medical school
Founder of that eponymous university, philanthropist Johns Hopkins, had counted on income from B&O Railroad stock to establish the medical school and recruit faculty. (N.B., the peculiar extra S was because his first name was actually a family surname – source.) However, the 1890s were economically volatile times and Hopkins only had funds to open the hospital but not the medical school. As documented in the history of the university, four daughters of the university’s original trustees offered to help, with conditions:

Martha Carey Thomas, Mary Elizabeth Garrett, Elizabeth King and Mary Gwinn, all unmarried, wealthy, well-educated and devoted to the new feminist movement – offered a deal. They would raise the $500,000 needed to open the school and pay for a medical school building, but only if the school would open its doors to qualified women. Arguments ensued, the pragmatists won out, and the women were given the go-ahead to try.
When the money was in hand by Christmas Eve, 1892, the Women’s Fund Committee added a strategic twist, making new demands that even the staunchest opponents of a coeducational school could not reasonably refuse. Garrett – who as daughter of the head of the B&O was able to donate about $350,000 to the effort herself – presented a list of stiff entrance requirements that would have to be met by any Hopkins applicant, male or female: proof of a bachelor’s degree, proficiency in French, German and Latin, and a strong background in physics, chemistry and biology. Hopkins’ leaders were taken aback; most of the demands appeared to have been lifted directly from an early letter by [first professor and dean, William Henry] Welch to University President Gilman – suggestions that even Welch, after he hired on, admitted he thought were impossible goals.

Yes, medical school standards varied widely at the time and these “impossible goals” pushed forward by the women established the new institution as one of the best in the United States.
To understand the prevailing attitude toward women in higher education, the following were the 1874 comments of Gilman’s colleague Charles Eliot, president of Harvard University, who called coeducation “a thoroughly wrong idea which is rapidly disappearing,” Hopkins trustees had Gilman call upon Eliot as a consultant on this issue:

“[S]tudents might fall in love, which could produce disastrous, socially unequal marriages; women would have trouble keeping up with the academic pace and hold up instruction for the men; the stress could prove so severe that the women might fall ill and destroy their chances of good marriages; and finally, a woman’s future was so different from a man’s that there was no point in educating them together.”

Thumbnail image for Sabin Smith College graduation.jpgUnfortunately, George Sabin’s mining company in Denver was also suffering financially for many of the same reasons that the Hopkins railroad investments delayed opening of the medical school. The 1890s were volatile economic times not to be matched until The Great Depression. As such, Florence could not afford to attend medical school after graduating from Smith College in 1893 (her senior picture is shown to the left) and would have to assume financial responsibility for any future education.
As a result, Sabin came back to Denver to teach at Wolfe Hall, where her sister Mary was already working since her own graduation from Smith two years earlier. In 1895, Florence returned to Smith to teach and then received a fellowship during the summer of 1896 to work at the renowned Marine Biological Laboratories at Woods Hole on Cape Cod.
With these experiences and now-sufficient savings, Sabin was able to apply and be accepted to Johns Hopkins Medical School for the 1896-97 academic year. Exemplifying the commitment of Hopkins to training female physicians, Florence was one of 14 women in a class of 45.
Sabin book American Women of Achievement.jpgWhat follows from her remarkable career is detailed at numerous sites on the web including a 1960 National Academies Press biography, the National Library of Medicine, and the Rockefeller Archive Center. But I detail these early life influences here because they are not widely accessible outside of archives at Smith College and the Colorado Historical Society and are covered only briefly in the 1960 National Academies biography. I learned most of the preceding story from a remarkable out-of-print 1990 book from a 50-book series entitled, American Women of Achievement. Written by New York freelance writer, Janet Kronstadt, this 101-page volume on Sabin can be purchased used on Amazon for only a few dollars, roughly the same cost as shipping.
The book and websites above chronicle the rest of Sabin’s remarkable life of medical achievement and public service but I’ll provide some of the highlights as follows.

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What’s the difference between HeLa and HeLa S3 cells? Part I: Launching the lab

Sabin Rockefeller portrait cropped.jpgWhen I first started my independent academic laboratory in 1992, it was in a brand new facility across the parking lot from a then 40-year-old building named in honor of the woman to the right. I took on a big teaching load from day one and while I had some cash left from the $50,000 start-up package, I didn’t hire a technician immediately. So it fell upon me to do all the ordering of the basic supplies to get the operation rolling. No problem, right? I ordered much of my own stuff as a postdoc so it should be no problem to get everything I need to start the lab from scratch.
One of the most common buffers used in molecular and cell biology labs is “Tris,” short for a base called tris(hydroxymethyl)aminomethane. By adding different amounts of hydrochloric acid to it, you can create buffers from pH 6.8 to pH 9 so it’s pretty versatile.
So, I opened the old Sigma catalog (this was when companies were only just starting to get their catalogs online). There were five varieties of Tris and nine varieties of Trizma®, Sigma’s brand of Tris base (there are now six and 15, respectively).
So which do I order? The ACS reagent grade >99.8%, the JIS special grade >99% or do I go for the BioUltra Trizma?
But the Bioultra Trizma comes in two forms, one for molecular biology and another for luminescence. I definitely needed a molecular biology grade tested RNase-free that I could also use for cell culture.
Hmmm, how ’bout the “Biotechnology Performance Certified, meets EP, USP testing specifications, cell culture tested, ≥99.9% (titration).”
And so, for each chemical I needed to start the lab I had to go through and evaluate why I needed one form over another, and what the difference was between all of the terminology.
When it came time to bring in the cultured cell lines for my work, I decided that I was going to start all of my cultures from an original, traceable stock obtained directly from a cell repository instead of the more common practice of soliciting colleagues around campus for hand-me-downs of their established lines. You never know where someone’s cells have been, how long they might have been passaged, whether they have been cross contaminated, or if they have latent mycoplasma infections.
Thumbnail image for The Immortal Life of Henrietta Lacks 250px.jpgSo I knew I needed HeLa cells – those ones we’re hearing all about these days from Rebecca Skloot’s New York Times-bestselling book, The Immortal Life of Henrietta Lacks, about the 31-year-old rural black woman whose cervical carcinoma gave rise to the first immortalized human cell line.
The two most common vendors for original cell culture stock are the American Type Culture Collection (ATCC) and the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), or German Collection of Microorganisms and Cell Cultures. There are others, including major national research institutes, and dozens of other vendors have modified cells for a variety of specialized uses.
ATCC is a private, non-profit organization that traces its roots back to 1925 when scientists realized a need for a central laboratory that distributed certified strains of microorganisms. If you isolate your own cell line that you wish to make available to the scientific community, you can deposit it with ATCC and they will handle requests for it from other investigators, using sales fees to support their operation.
Not only does ATCC serve as a central repository but it also contributes to the continuity of the biomedical research enterprise. I had a physician-scientist colleague a few years back who was closing his research lab and moving to private oncology practice. But he had developed a series of very useful drug-resistant clonal populations of two, common human leukemia lines. These are very useful cells for investigating why cancer cells develop tolerance to drug therapy but since there would be no one left to distribute them, he deposited them with ATCC (example).
OK, so back to 1992: I open the ATCC catalog (again, before it was online) and, hmm, you’ve got HeLa cells (catalog designation CCL-2). Great. Let’s order ‘em up.
But then there are also HeLa 229 (CCL-2.1), and HeLa S3 (CCL-2.2).
Hrumph. I just want some freakin’ HeLa cells – what’s up with these other ones? They all kind of look the same, all from the same woman, all grown in the same medium.
So what the difference?
In her Los Angeles Times interview last month, Skloot remarked that the Lacks book began with a manuscript she was planning to meet the requirements of her MFA at the University of Pittsburgh:

“I was in class, and I got out a piece of paper and I wrote at the top ‘Forgotten Women in Science,’ ” she remembers. She planned to do 12 essays. “Number 1, I wrote Henrietta Lacks, and then I was like, hmmm.”

So over a series of posts this weekend, I wish to tell you about a woman in science indirectly related to HeLa cells. She may not necessarily qualify as a “forgotten woman of science” but her story is perhaps not well-appreciated today because her contributions occurred so long ago.
Florence Rena Sabin, MD (1871 – 1953), a daughter of a Colorado coal mining family, became a female pioneer in medicine and public health. With the simple notation of “S3″ she is forever linked to the first clonal population of these cervical cancer cells from the poor Virginia tobacco farmer.
Image credit: Sabin color portrait from Women in the Rockefeller Archive Center

Epigenetics Alert! UStream “Office Hours” with Duke’s Randy Jirtle today at noon EST

Here’s a great, last-minute opportunity to interact one-on-one with a major player in the field of environmental and dietary influences on gene expression. From the Duke University Office of News and Communications:
Thumbnail image for jirtle_280.jpgCharles Darwin famously reasoned that genetic traits change over many generations through natural selection, but the new field of “epigenetics” is finding that nurture can change nature more directly. Duke Professor Randy Jirtle will discuss epigenetics and answer viewers’ questions during a live “Office Hours” webcast interview at noon (17:00 GMT) Friday, Jan. 22, on Duke’s Ustream channel.

To ask a question of Jirtle in advance or during the session, send an email to live@duke.edu, post a comment on the Duke University Live Ustream page on Facebook or tweet with the tag #dukelive.

The science of epigenetics explores the molecular activity that influences the expression of genes. Jirtle emerged as a pioneer in the field with a 2003 study in which he showed how the genetic expression of a baby mouse’s fur color could be altered by changing its mother’s diet during pregnancy. Recent stories on epigenetics by NOVA, Time and the Washington Post have cited his research. Jirtle’s lab chronicles developments in the field on the Geneimprint website

How much should you know outside of your field?

I’m a bit under the weather today but I wanted to at least share with you an interesting career development consideration pointed out by the always-excellent medicinal chemist blogger, Derek Lowe at In the Pipeline.
In his post, What Should Non-Chemists Know About Medicinal Chemistry, Anyway?, Derek posits:

Here’s a topic that I was discussing with some colleagues not too long ago: how much do we need to know about each other’s specialties, anyway? I’m assuming that the answer is “more than nothing”, although if someone wants to make the zilch case, I’d be interested in hearing it done.

A nice comment thread has developed there. Lowe writes from the perspective of a chemist in a pharmaceutical company but I believe that his considerations extend to academic research as well, especially with the increased emphasis on interdisciplinary and translational research.
I consider myself fortunate to have been trained in pharmacology when “true” pharmacology departments were more abundant (i.e., not just a bunch of in vitro biochemists). Having to interact with chemists, stop-flow enzyme kineticists, physiologists using in vivo and organ bath systems, and physicians with research laboratories, I feel that I can be somewhat conversant on a variety of issues outside my immediate research area. Being able to explain the chemistry of glucuronidation sites or the clinical pharmacology relevance of high plasma protein drug binding are obvious extensions of what I should know. I’ve also learned to recognize when it may not be appropriate to ask a chemist colleague for more than a milligram or two of a new compound.
But knowledge beyond that, I think, is even more important for my research program and department. I tell students that you never know where you will end up working and a breadth of knowledge is important to develop even while pursuing the myopic drilldown of PhD dissertation research. Particularly if one ends up in a drug company, you will have to interact often with team members across the drug development pipeline and many go/no-go decisions will be made because of limitations outside your area, no matter how novel your pharmacological target may be. And yes, it is a problem in trying to make a drug out of a compound that only dissolves in DMSO.
So I’ll throw open Derek’s question to those of you in academia: How much chemistry do you expect biologists to know or how much biology should we expect chemists to know? Some of it is simple courtesy and helps develop mutual respect among research colleagues. But some of my colleagues think that the wider you can think, the more likely it is for your research program to make greater impact. (I can’t find it right now but I recall Brown and Goldstein holding forth somewhere on how a strong basis in chemistry is essential for physician-scientists). There’s no one right answer and I am certain there is no consensus, and I feel that the need for breadth will vary based on how far along one is in one’s career.
But in your area, how much do you expect yourself and your trainees to know in areas afield?

NIDA researchers Hinds (Kentucky) and Torres (Pittsburgh) given Presidential Early Career Award

Hearty congratulations this morning to a group of early-career investigators who received this award yesterday in Washington, DC:

The Presidential Award for Early Career Scientists and Engineers was established in 1996 and is the highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers. [emphasis mine] Awardees are selected on the basis of two criteria: pursuit of innovative research at the frontiers of science and technology; and a commitment to community service as demonstrated through scientific leadership, public education or community outreach. Winning scientists are awarded a research grant for up to five years to further their studies in support of critical government missions. This year, eleven federal departments and agencies nominated 100 young scientists and engineers who showed exceptional promise for leadership in science and technology. Drs. Hinds and Torres are 2 of 12 NIH grantees to receive the prestigious PECASE award.

According to the NIDA press release:

Bruce J. Hinds, III, Ph.D., associate professor of chemical and materials engineering at the University of Kentucky, is being recognized for his work to improve the delivery of drugs that treat nicotine dependence through a novel skin patch. Gonzalo E. Torres, Ph.D., assistant professor of neurobiology at the University of Pittsburgh School of Medicine, is being cited for his research on cellular and molecular regulation in the brain and its relationship to psychiatric disorders and drug addiction.

As I’ve remarked previously, NIDA is one of the NIH Institutes and Centers with a very active public relations and news office so this was the only press release I found. However, ten other NIH-funded scientists also received the PECASE; here’s the complete list:

Thomas P. Cappola, M.D., Sc.M. (University of Pennsylvania School of Medicine)
His research on the use of genetic and genomic approaches for studying ventricular remodeling in humans is supported by a grant from the National Heart Lung and Blood Institute (NHLBI).
Pablo A. Celnik, M.D. (Johns Hopkins Hospital)
His research on the underlying mechanisms of plasticity in the central nervous system in order to develop novel therapeutic approaches that promote recovery of function following an injury is supported by a grant from the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD).
Felicia D. Goodrum, Ph.D. (University of Arizona)
Her research on hematopoetic progenitor cells and their influence on latency in human cytomegalovirus infections is supported by a grant from the National Institute on Allergy and Infectious Diseases (NIAID).
Bruce J. Hinds, III, Ph.D. (University of Kentucky)
His research on the use of gated carbon nanotube membranes for transdermal drug delivery is supported by a grant from National Institute on Drug Abuse (NIDA).
Helen H. Lu, Ph.D. (Columbia University)
Her work on the use of biomimetic scaffolds to promote chondrocyte-mediated regeneration of the interface between soft tissue and bone is supported by a grant from the National Institute on Arthritis Musculoskeletal and Skin Diseases (NIAMS).
Ulrike Peters, Ph.D., M.P.H. (Fred Hutchinson Cancer Research Center)
Her research on selenium and the interaction of genetic variations and nutrition on cancer prevention is supported by the National Cancer Institute (NCI).
Jeremy F. Reiter, M.D., Ph.D. (University of California at San Francisco)
His research on the role of the proto-oncogene Smoothened and its interaction with the primary cilium in the development of cancer is supported by a grant from the National Institute on Arthritis Musculoskeletal and Skin Diseases (NIAMS).
Marisa Roberto, Ph.D. (The Scripps Research Institute)
Her research on neuropeptides, neuronal function and synaptic communication related to alcohol and other drugs of abuse is supported by a grant from the National Institute on Alcoholism and Alcohol Abuse (NIAAA).
Erica Ollmann Saphire, Ph.D. (The Scripps Research Institute)
Her studies on the role of glycoproteins in the pathogenicity and immunogenicity of Ebola virus is supported by a grant from the National Institute of Allergy and Infectious Diseases (NIAID).
Oscar E. Suman, Ph.D. (Shriner’s Hospital for Children, University of Texas Medical Branch)
His research on supervised and structured aerobic and resistance exercise on muscle mass and bone mass in severely burned children is supported by a grant from the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD).
Kristin V. Tarbell, Ph.D. (National Institutes of Health Intramural Research Program)
Her research on the role of dendritic cells on T cell mediated autoimmune diseases such as diabetes is supported by the National Institute on Diabetes and Digestive and Kidney Diseases (NIDDK).
Gonzalo E. Torres, Ph.D. (University of Pittsburgh)
His research on cellular and molecular regulation of monoamine transporters in brain and the relationship to psychiatric disorders and drug addiction is supported by a grant from the National Institute on Drug Abuse (NIDA).

We often don’t do enough in the biomedical sciences to promote the work of early-career investigators. But these people are our future. Their current work and future promise should be promoted and, more importantly, supported financially.
Congratulations to all of this year’s Presidential Early Career Award recipients.