Women in science and medicine

Amy Bishop indicted for 1986 shooting murder of brother

terrasig — Wed, 16 Jun 2010 16:59:26 +0000

Amy Bishop indicted for 1986 shooting murder of brother

Was just checking the old SiteMeter stats before foraging for dinner and saw a surge in search hits for "Amy Bishop."

Yup. Lo and behold she has been charged with murder - for the 1986 death of her brother.

From an article an hour ago by Donovan Slack and Shelley Murphy at the Boston Globe:

The slaying of Seth Bishop was declared an accident by Norfolk County authorities at the time. But questions were raised about the investigation after Bishop, a college professor, was charged in February in a shooting rampage at the University of Alabama Huntsville. Three of Bishops' colleagues were fatally shot and three wounded in that case.

[District Attorney William R.] Keating said an indictment warrant has been lodged with Alabama authorities. He indicated that he would give the Alabama triple murder case priority. Asked whether Bishop would ever be tried in Massachusetts for murder, Keating said, "You never know.''

. . .Shortly after the Alabama shootings, Keating launched a review of the Braintree slaying and concluded that Bishop should have been charged at the time with assault with a dangerous weapon, unlawful possession of a firearm and illegal possession of ammunition.

Keating also found that police reports, along with crime scene photos, suggested Bishop may have intentionally shot her brother. One photo of her bedroom, where she had loaded the 12-gauge shotgun, showed a National Enquirer article chronicling actions similar to Bishop's that day. The article reported that a teenager wielding a 12-gauge shotgun killed the parents of actor Patrick Duffy, who played Bobby Ewing on the television show, "Dallas," and then commandeered a getaway car at gunpoint from an auto dealership.

Many a "what if?" reverberating across the Southland this evening.

The following list provides our previous posts on the gut-wrenching Amy Bishop murders at the University of Alabama - Huntsville:

UA Huntsville Dr. Amy Bishop holds active NIH R15 AREA award (Feb 13, 2010)
Amy Bishop UAH case: What role should personality or collegiality play in tenure decisions? (Feb 14, 2010)
Insider's take on Amy Bishop's gender-discrimination case (Feb 26, 2010)

terrasig Wed, 06/16/2010 - 12:59

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What does it take to knock off K2 Spice readership?

terrasig — Wed, 02 Jun 2010 05:32:33 +0000

What does it take to knock off K2 Spice readership?

Just the other day, I wrote about how DrugMonkey and I have experienced unprecedented and sustained blog traffic for posts we wrote in February on K2 Spice, one of a couple of marijuana-like "incense" products still sold legally in the United States.

Every morning, I dial up my SiteMeter blog statistics and take a look at what posts readers first land upon when coming to visit the humble world headquarters of Terra Sigillata.

Last week, 2,700 to 2,800 of the 4,000 most recent hits were landing on our February K2 Spice post. (You will also note below the sad state of my readership in that posts on Stiff Nights erectile dysfunction supplement and Horny Goat Weed products are the next most popular direct hits.)

Finally, one post has knocked it out of the top spot after nearly four months:

Monday's post about the memorial unveiling of the gravestone for Henrietta Lacks this past weekend.

I have been completely overwhelmed by the interest in this story. This widespread attention would not be possible without the Facebook and blog referrals by author Rebecca Skloot, The New York Times Science page, and the enthusiastic Twitter referrals by other writers who I respect greatly such as David Dobbs, Sara Goforth, Mike Rosenwald, T. DeLene Beeland, Ted Winstead, scribbler50, Eric Ferreri, - as well as the dozens of you sci/med bloggers and folks from other walks of life who found this post worthy of recommending to your friends.

Please accept my apologies if you were not mentioned by name - I don't have Bora Zivkovic's flair for aggregating and linking to every referral but you have my gratitude for further popularizing the story of Henrietta Lacks and her family.

And for those of you so inclined, here are images of the memorial program that weren't included in the last post:

terrasig Wed, 06/02/2010 - 01:32

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Hey Abel, glad the NYTimes widget sent some traffic your way, but I just thought I'd show you where I first saw the link to this post: the twitter feed of buyk2incense.

As I was saying over at Obesity Panacea about the difficulty of getting rid of sham weight loss ads from our automated ad network, algorithm-based advertising occasionally makes exactly the wrong decisions based on keyword optimization.

But, like spam, the sheer number of people who will click on anything related to sex, drugs, or free money is enough to make such errors totally irrelevant. This phenomenon ensures that Jonah Lehrer's article on gay animals and this short piece on women watching monkey porn will forever be two of SeedMag's most popular articles. You can imagine the search terms that got people there.

You are more than welcome, TS. Was a especially nice post, giving us both the flavor of the day and a feel for how powerfully Lacks' story, related so richly by Skloot, can affect not just you as a researcher and person but your relations with many circles of society. (Plus the pictures were cool.)

I take it this means you're finally finally over that cold!

Evan Lerner - note to self: sex, drugs, free money - but no rock 'n' roll???

David - you are too kind yet again but, yes, my inhaled corticosteroid-induced dysphonia has resolved to the point that I was actually able to speak in church Saturday. I'll be starting speech therapy in two weeks to strengthen my vocal cords and learn good vocal hygiene.

Oh, and by the way: K2/Spice is sadly back on top in this morning's ranking of the last 4,000 hits: K2 over Henrietta 1331 to 781.

Marking the magnificent memory of Henrietta Lacks

terrasig — Mon, 31 May 2010 12:02:09 +0000

Marking the magnificent memory of Henrietta Lacks

In addition to my own photos herein, Tom McLaughlin posted a nice slide show of the day at his South Boston News & Record.

Despite two trees that snapped and fell in my driveway within six feet of my car in an impressive thunderstorm Friday evening, I drove on Saturday morning to Clover, Virginia, for the dedication of a gravestone that finally marks the final resting place of Henrietta Lacks, a concrete honor, if you will, to recognize the source of one of the most valuable medical tools of the 20th century and today.

For those who are not regular readers, Henrietta Lacks was a rural tobacco farmer, mother, wife, daughter, sister, and friend from southern Virginia who developed an unusually aggressive case of cervical cancer while living in Baltimore in 1951. While being treated at Johns Hopkins University, surgeons excised pieces of her tumor in an ongoing effort by the laboratory of Dr. George Gey to establish a continuously growing human tumor cell line in culture, a feat that had only been previously accomplished with mouse cells. Ms. Lacks's cells are today known by the name, HeLa (hee-luh), and have been used from the fifties in testing the effectiveness of the original Salk polio vaccine up through today providing the basis for the new cervical cancer vaccines. I would not be overstating the case to say that most biomedical scientists have at one time or another worked with HeLa cells.

However, the identity of Henrietta Lacks as the unknowing donor of the cells that gave rise to so many medical discoveries - a poor Black woman, mind you - as well as the story of her family and their travails at the hand of the medical establishment had largely gone untold until the 1980s, even among scientists themselves.

But with the help of the family - especially Henrietta's late daughter, Deborah - scientists, historians, and her own tenacious investigative skills, journalist and author Rebecca Skloot spent the last ten years researching and gorgeously crafting a book on the HeLa story that has become this year's best-selling non-fiction gem, The Immortal Life of Henrietta Lacks. If you have not yet read the book, you are missing out on what Dwight Garner of The New York Times called, "one of the most graceful and moving nonfiction books I've read in a very long time."

A black woman, a white boy, and a PhD
My own interest in the story extends beyond my general fascination with the history of science and medicine. It is far more personal.

As I wrote in November on the 20th anniversary of my PhD dissertation defense, HeLa cells were the primary experimental system for my study of the anticancer drug target, DNA topoisomerase IIα. Moreover, HeLa cells were also the source of genomic DNA I needed to understand the enzyme's regulation when I started my own laboratory in 1992. They ended up providing the topic of the first published paper from my independent group: me, my first PhD student, and first technician.

So when I learned that from the South Boston (VA) News & Record that the Lacks family had planned a memorial dedication service for Ms. Lacks's headstone, I just had to attend.

The headstone was provided by a Morehouse School of Medicine donation from Dr. Roland Pattillo and his wife, Pat. Dr. Pattillo is an ob/gyn physician-scientist at the Morehouse School of Medicine who has largely been the medical guardian of the Lacks family and who provided the entré to Ms. Skloot after she convinced him of her sincerity in telling the story of the family and their matriarch. Pattillo is also himself a notable scientist of historic stature and a living connection to Dr. George Gey. Among his own four decades of accomplishments, Dr. Pattillo worked at Hopkins with Gey in the sixties on the hormonal aspects of neuroendocrine tumors and, as detailed in a 1968 Science paper, established the BeWo choriocarcinoma cell line, the first immortalized line to produce human chorionic gonadotropin (hCG). hCG is the hormone produced by the placenta that is detected in clinical and home pregnancy tests.

To the right is Dr. Pattillo at the gravesite with an unnamed science blogger showing off his 20-year-old dissertation. To the right are two Lacks family members sharing addresses on top of Skloot's book. You'll note that the gravestone is also in the shape of a book, representing the many stories that have come from the legacy of Henrietta Lacks.

The service began at St. Matthew Baptist Church in Clover, the church where Henrietta had been a member since 1932. My intention had been just to drive up and quietly pay my respects, maybe even get a photo of my dissertation at Henrietta's gravesite. Such intentions were derailed by one of the nice usherette ambassadors at St Matthew who asked if I was a dignitary (no) but then insisted that I sit with the press and go have a word with the pastor, Reverend Alfred Chandler. Reverend Chandler then asked that I speak to the standing room-only congregation that included dozens of Lacks family members about how my personal and professional life had been touched by the woman from Clover. Time was set aside for friends and family to share such brief reflections.

Just as an aside: I've now lived in the South for a third of my life. For the last ten years I've lived in a town with an equal 45% African-American and White population and am a prof at a historically-Black university. It never ceases to amaze me how warmly welcoming the Black community has been to me, everywhere from Virginia to Florida, and in a manner that belies the converse treatment of the community for centuries. In fact, if I could join a Black congregation, I'd probably still be going church.

I was beaming when I learned that the first scripture reading was the famous Ecclesiastes passage (3:1-8) upon which Pete Seeger wrote Turn! Turn! Turn! (The song was made popular by The Byrds in 1965 and discussed on this blog, with a Byrds reunion performance, here.). In the context of the other speakers, it was clear that this day was one to heal, build up, laugh, dance, and, most certainly, a time to embrace - I haven't been hugged so much since my last visit with my large family from New Jersey.

Opening words on behalf of the Lacks family were offered by Kimberley Lacks, daughter of Sonny Lacks, granddaughter of Henrietta Lacks. Kimberley stressed a major point that Skloot's book did so extraordinarily well: for us to remember that her grandmother was a real woman who worked in the fields, cooked, danced, and wanted the world for her children like any other parent.

Kimberley then expressed the families gratitude for those who did just that, first and foremost thanking Rebecca Skloot for her ten-year journey with the family and scientists worldwide to bring the Henrietta Lacks story to the attention of all people, not just us in science and medicine.

Then, Kimberley said something I want all writers to know:
"Thanks to the media for bringing the story of Henrietta Lacks to the world."

I joked with the writers and TV folks there as to when the last time was that they were expressly thanked for their work. But remember this, my journalism friends: you do make a difference. Because of this essential role you play in society, we just have to figure how to make the profession more financially viable for as many of you as possible in the new media landscape.

I had the distinct pleasure of being seated next to Attorney William Bryant Claiborne and his wife. Attorney Claiborne is a proud graduate of Virginia State University, a superb HBCU in Petersburg, and then earned a law degree at the University of Virginia. His colleagues thought he was out of his mind to come back to his rural home to practice but he reminded me that his home folk need legal services just as badly as those in Richmond and DC. Mr. Claiborne certainly walks that talk - also serving on the Halifax County Board of Supervisors. In this capacity, he presented the Lacks family (below) with a resolution honoring Henrietta Lacks, saying "we are so proud she lies in our county."

A rare experience for a scientist
While anxiously reflecting on the comments I was about to give, I recalled the fact that I felt embarrassed that my dissertation included nothing more about HeLa cells than the paragraph excerpted in this post, and certainly nothing about the woman from whom the cells were derived. Twenty years later, this is an even more glaring omission. So, I used the opportunity to thank the family for the gift of their matriarch. While I couldn't change the past treatment of the family, I can play a part in moving forward and was therefore honored to be asked by Rebecca Skloot to serve with Dr. Pattillo on the board of The Henrietta Lacks Foundation to bring scholarship support to today's young descendants. (Rebecca is donating a portion of book proceeds to the Foundation.)

And I didn't even think about this until I was standing before the congregation - I told the family that I would be honored for them to sign my dissertation because this PhD work was as much theirs as mine.

I also had a few other things to say regarding the impact of HeLa cells on me personally and professionally and on other scientists and physicians around the world and how literally world-famous Henrietta Lacks is now. This gift of their matriarch, through her own suffering, has facilitated our efforts to relieve the suffering of literally millions of other people. The use of HeLa cells (and other cell lines overtaken by HeLa cells) led to the development of some drugs that treated my own mother who was stricken with a lymph node-positive breast cancer when I was a junior in college, stimulating me to become a cancer researcher and allowing her to now be a 26-year breast cancer survivor.

I was also sure to address the young people in the audience, family and otherwise, to encourage them in science and medicine and offered our them an open invitation to visit with us in our laboratories and classrooms in the Research Triangle area.

These words got some applause and a few Amens and "Praise Jesus!" - affirmations and feedback that we rarely get in the context of university auditoriums and seminar programs. Knowing more about the Black church since moving to the South makes these affirmations even more meaningful.

I do not yet have the writing skills to adequately express how moving this experience was for me to have the opportunity to face the family and express my gratitude that the life I have today - the wife, daughter, house, guitars - stems from a story of injustice across the decades. Because of today's clinical guidelines for anonymizing human tissue specimens, we most often have no idea as to who exactly provided the biological research tools we use in the laboratory. But to be hugged by Sonny Lacks and literally and philosophically embraced by so many of the family is an experience I will never forget.

And now that several dozen members of the Lacks family have autographed and inscribed my dissertation, it somehow seems more complete.

Many of the family also put in their telephone numbers, quite ironic knowing how difficult it was for Rebecca to even get family members to return her phone calls for the first couple of years of her writing.

The guest speakers that followed were uniformly outstanding beginning with Rev. Kevin Chandler, president of the Halifax NAACP chapter. Rev. Ronnie Womack, mediator of the Banister Missionary Baptist Association, gave us some of the most motivating old-time preaching, stressing that the day was one for unification - implying, to me at least, that we were there to recognize that the gift of a Black woman has impacted the lives of all racial and ethnic groups - and "that when CNN rolls across the bottom of the screen that a cure for cancer has been found," that Henrietta Lacks will be part of that story.

The highlight for many of us was when Dr. Roland Pattillo took the pulpit to humbly note his role in the day and the generosity of he and his wife in providing the gravestone for Henrietta Lacks together with the Morehouse School of Medicine. In noting that over 60,000 peer-reviewed publications have made use of HeLa cells, Pattillo told us that even today, another such paper is published at a rate of one every two hours. Dr. Pattillo is deserving of his own blog post and I look forward to telling more of his story.

At the other end of the spectrum was the next speaker, a remarkable young man, freshman congressman Rep. Tom Perriello (I can say that because he's about a decade my junior). An undergrad and law graduate of Yale University, this native of Virginia's 5th district reflected on his work in West Africa where polio continues to afflict millions despite the millions saved in Western nations thanks to the role HeLa cells played early in vaccine development. Perriello excerpted a resolution he read into the Congressional Record last Friday honoring Henrietta Lacks ("Honoring Henrietta Pleasant-Lacks" full text).

As a side note, I drove past many advertisements for his Republican opponent, Robert Hurt, that read, "HURT U.S. Congress."

My immediate thoughts were, no thank you - you've hurt it enough already.

Perriello is an energetic politician who causes Republicans to froth because of his dedication to the military, international relations, workforce development, and establishment of faith-based aid groups while also putting forth such heresy and tyranny as affordable health care and asking his campaign workers to also "tithe" hours on community service projects unrelated to the election. His district runs from the North Carolina border to north of Charlottesville, home of the University of Virginia, where his support is quite strong. I took it as a compliment that Rep. Perriello stopped me afterward to say I'd make a good politician - if it meant being like him, I would.

Reverend Alfred Chandler then closed with words that I think we can all do well to remember - that when we see someone in our community and feel an urge to pass judgment, bear in mind that we have no idea as to that person's story.

Gravestone dedication
We were then off to the Lacks family cemetery on the property of the old home-house down Lacks Town Road, an absolutely beautiful stretch of rolling farmland. The photo below was taken looking south from the intersection of Mt. Laurel and Lacks Town Rd.

About 100 people remained from the church service to dedicate the Henrietta Lacks gravestone just to the left of that of her mother, Eliza Pleasant. Another gravestone also being dedicated was that for Elsie Lacks, Henrietta's daughter who died at age 15 at the Crownsville State Hospital, known then as The Hospital for the Negro Insane of Maryland. The story of Elsie and the visit there by Rebecca and Deborah Lacks has been cited by many as one of the most emotional parts of Skloot's book.

With all of the press attention, Sonny Lacks made it a point to introduce to all NPR "Butch" Forester, the groundskeeper who maintains the previously overgrown Lacks family cemetery in its now peaceful and reverent state.

I also had the chance to walk over to the home-house where Henrietta, her husband David, and children lived. It's tougher to see now than in the winter due to the trees and undergrowth but you can get a better glimpse of it from the photos then at Rebecca Skloot's website.

And before heading back on the road, the church and family had a nice repast dinner with fried chicken, green beans, potato salad, macaroni salad, meatballs, rice, and - nom! - chocolate cake.

Put simply, this was the single most moving day in my life as a scientist.

A roundup of press cover of the Henrietta Lacks headstone memorial dedication:

Lauren Compton and her videographer from WSET-TV in Lynchburg wrote this article and filed a segment from the station having only an hour to get back to the studio, thereby missing the repast. Beyond being a superb reporter, Ms. Compton did not have to refer to the songsheet to sing the words to the hymns.

I had a lovely time chatting with Denise Watson Batts of the Hampton Roads Virginian-Pilot who wrote "After 60 years of anonymity, Henrietta Lacks has a headstone." Denise also had an excellent interview earlier this month in Baltimore with Sonny Lacks, eldest brother, Lawrence, and cousin Sadie Grinnan.

A superb writer, editor, and a fine gentleman, Tom McLaughlin, wrote this nicely detailed article for his South Boston News & Record. Although the press took numerous photographs at the services, only Tom put up a slideshow of 49 photos within that story. Tom and his mother, Sylvia O. McLaughlin, editor of the News & Record, are extremely proud of their newspaper and readers know that I am a huge fan of local news. The level of detail that local writers and publishers puts into such stories (or should) reminds us of the importance of sustained local reporting. I'm grateful to Tom and his Mom for sending me home with a few issues of their paper that covered Skloot's book and the Lacks family stories. Tom's own review of the book speaks from the viewpoint of a Southside Virginia native.

Tim Saunders from WDBJ-TV in Roanoke, Virginia, birthplace of Henrietta Lacks filed this article and video, "Halifax County community pays tribute to world famous native," today.

A brief note appeared on June 1 on the website of Essence magazine.

Many thanks also go to Melissa Bell from The Washington Post and graduate of Northwestern University School of Journalism who patiently listened to my stories and whose work I look forward to reading.

I also want to publicly thank my lovely wife, PharmGirl, MD, and the illustrious PharmKid for understanding how much being away for this event meant to me. As always, I was on science time and a quick "couple of hours" trip took all of Saturday, a holiday weekend day we really needed to spend together after I've been out of town and away for other university events.

terrasig Mon, 05/31/2010 - 08:02

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Thank you very much for giving us this wonderful post.

What a beautiful story and an amazing post. You do all of us a proud by speaking with such feeling and authenticity. Thank you.

Thank you for telling this story, and describing the impact of Henrietta's life on your career as a scientist.

Thanks for sharing your wonderful photos, and this continuation of the Henrietta Lacks story, Abel. After hearing interviews with Rebecca Skloot on the radio several times, it's been in the back of my head that Lacks was quite young when she died of cervical cancer - but seeing that gravestone makes it especially poignant, somehow.

Thank you for this wonderful post. I have printed it and put with my Rebecca Skloot book about Henrietta.

Awesome that you were able to be a part of this, Abel. I read the book, and just loved it. The headstone is beautiful.

What a pleasure it was to read your entire post and see the photos from this long overdue and wonderful event. One thing you got wrong -- you DO have the skill to express in words how moving this was for you, because it comes through in your every sentence. So glad you go to have this experience, and thanks for sharing it with others.

Nice post! Just told Mr. Bill to read it!

Glad you were able to attend this event, Abel. I've lent my copy of Skloot's book to several colleagues and all of them said they had absolutely no idea where HeLa cells originated, why the cells were so named, and that they were reduced to tears at the unjustices done to the Lacks' family.

What a wonderful post about the memorial and dedication. My family is from Clover, and we had no idea about this wonderful woman until we saw in the paper about her tombstone placement. Next time I go back to Clover I want to head to Lackstown and place flowers.

I can't help but comment on your glowing review of our "Congressman" though. He is not from the district, he is a Yankee who came down and ran a smear campaign against our longstanding Congressman and managed to get elected because of the Presidential election. He is not well liked except in Charlottesville. Don't believe everything you hear.

Great post Dr.Kroll. Very moving!

Thank you for sharing your experience so vividly in this post!

Very, very nice, DM. A fine account of a splendid day.

Greetings, Dr. Kroll, it was such a pleasure to meet and talk with you at the Memorial Dedication for our grandmother. Our thanks and gratitude go out to people like you who took the time to attend this event. It was so memorable and I for one will not forget the many people that I had the opportunity to meet. I was thinking about a comment my uncle Lawrence made, "That GOD had a plan in his mother's passing". AND if you think about all of the lives that she has touched, from the cures of diseases to people like you. Who took an interest in her cells and became a successful doctor and still to this day, lives are being affected. Our family, would like to THANK YOU for such a beautiful post, and we will keep in touch. Please thank your family as well for allowing us to have you in attendance for this event. Best Regards

Abel, this is quite simply one of the most beautiful and well written posts I've ever read. On so many levels. Bravo, sir, and bravo to the family and spirit of Henrietta Lacks!

Once again, this story has brought me to tears. Thank you for sharing your day with those of us who could only be there in spirit.
And thanks to the Lacks clan for Henrietta's gift to humanity and their patience with the world's failure to acknowledge it...until now.

Wow...What a re-cap of the dedication! We drove down from Harrisburg Pennsylvania to attend and would not have missed it for the world.

Thank you for such a complete article.

Earl

Many thanks to all of my friends, old and new. I still don't feel that I completely conveyed just how remarkable this day was for me - certainly one that I will never forget for the rest of my life. (But thank you, Lisa Romeo @7, for your vote of confidence!).

First and foremost, Ms. Lacks @14 - Thank you again for being so welcoming of me on such a special day of celebration for your family. I consider it an honor and am ever so glad to be able to tell this story in this post and in others I've written on the blog over the last year.

Ms. Lacks @14 and Mr. Wilbourn @17 - I do have to say it was overwhelming to meet everyone at one time - the Clover, Baltimore, and Harrisburg Lackses. I could have easily spent hours talking with any one of you. I know that there will be other events and I very much look forward to participating and spending more time with you wherever and whenever I can. But please be sure to take me up on my promise to help the young folks in the family with their career plans, regardless of whether they include science or medicine.

anjou @8 - It is your Bill who has served for me as an example of how to hold in reverence all of those who came before us in the field of oncology therapeutics.

Professor in Training @9 - Your comment is exactly the reason I started my academic endorsement of the book with the statement, "No student or biomedical scientist should be permitted to broach the barrier of a cell culture hood without reading Rebecca Sklootâs, The Immortal Life of Henrietta Lacks."

Rasco from RIF @5 - Now *that* is an honor - thank you!

Barn Owl @4 - I was also reminded of just how young and vibrant Henrietta must have been when she died by looking at her granddaughters who are around 31 with their little ones.

Pascale @16 - What a perfect way to express to the Lacks family what so many of us feel: "And thanks to the Lacks clan for Henrietta's gift to humanity and their patience with the world's failure to acknowledge it...until now."

David Dobbs @13 and scribbler50 @15 - Your comments make me blush coming from two people whose writing I admire and aspire to (and fine gentlemen as well!)

Rose @10 - I'm so glad that you came to learn about the story here at our blog. What a wonderful honor and place in history for your hometown. But, goodness me, I hesitate to get much into politics more than my admiration for Congressman Perriello the man. He really is from Ivy, Virginia, and went to Yale for undergrad and law school, well, because he was smart enough to get into Yale. In fact, the smearing actually came instead from the campaign of Perriello's opponent, Rep. Virgil Goode, who depicted the challenger as a "swarthy New York liberal." (btw, Yale is in New Haven, Connecticut.)

Of course, I'm wary of any politician from any party but I was very impressed by his work to introduce the congressional resolution and in the depth of knowledge and sincerity of his comments on Saturday.

But, yes, please do go to the Lacks Town gravesite and lay flowers next time you are home. It is a beautiful site and a fitting resting place for a most noteworthy woman and her family.

Tremendous, David. Thank you for this moving post about your trip. Both are fitting tributes, and I feel privileged to share in this story.

Dear Dr. Pharmboy:
This is a remarkable story and thank you for bringing your link into the narrative. This was a wonderful gesture on your part. The messages left witnin your thesis are quite moving, best to you and your work!

Thank you for a wonderful coverage story. I have just finished "The Immortal Henriette Lacks" and find greta satisfaction that there has been recognitation of her life and contribution.

How can we say thankyou to a great man who did not care to just write a thesis but cared to reach out and give his thanks and graditude. Once again on the behalf of my family the Lacks, we like to thankyou for coming to our memorial. Just you acknowleding HeLa as not just a cell or thesis but a mother, wife,grandmother, great grand, friend and most important a person means alot.

I see orher family members was just as excited like myself to say how great you are and give you thanks. Within the Lacks family we are forever thankful,we do hope to see you and your family again at our black tie affair as well as your family. You can contact my daughter at www.spencerveronica50@gmail.com for more info. thanks again!

I think your writing skills are just fine, Abel. You brought a tear to my eye and a lump to my throat. Thanks.

Its important to give Henrietta Lacks her due important as a donor.

Hi... I didn't read all that you wrote. I stopped when you said, "In fact, if I could join a Black congregation, I'd probably still be going church." Why can't you? I am a European American woman, and I have been blessed twice in my life to serve on the staff of African American congregations. I also found them very welcoming places, and places where my spirit was nourished and inspired. I think you should do it!

Nature asks eight "experts" about Venter's prosthetic genome work

terrasig — Sun, 23 May 2010 08:45:02 +0000

Nature asks eight "experts" about Venter's prosthetic genome work

Men. Check.

White. Check.

Grey. Mostly. That dude must use color.

Beards. Only two. Maybe three. Aw, hell, Church's makes up for the rest.

Article here.

Ed Yong (Asian-British, man, young, dark hair, no beard) also lists a great wrap-up of the week's commentary on the work.

terrasig Sun, 05/23/2010 - 04:45

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*sigh*

just b/c they're old white dudes doesn't make them not experts

and just b/c ed wrote an article about it doesn't make him an expert

8 old white dudes and Woese not among them? That's just BORING. (Woese on Venter is HILARIOUS, always)

All those white people look the same to me ;-p

It's all about the beards. Doesn't matter the specialty - sociology (Durkheim), economics (Marx), psychology (Wundt), biology (Darwin)... I could go on, but I don't have to. So, only a couple of them are credible... amirite?

Aside from the beard, Church also deserves an award for his penetrating stare. If I were a gene faced with that look I'd give up my secrets too.

Ah, the old days with Mom: baking, knitting, extracting DNA

terrasig — Mon, 10 May 2010 06:02:19 +0000

Ah, the old days with Mom: baking, knitting, extracting DNA

I did not turn on the computer yesterday (yes, it was glorious) so I missed Mother's Day coverage in our local newspaper. When we returned home, I was happy to see that on the front page of the print copy the dean of Duke School of Medicine, Nancy Andrews, MD, PhD, was featured with her daughter in the lab on their fun Saturdays together.

Also cited and pictured in the article was Duke vice dean for research and professor of pharmacology and cancer biology, Sally Kornbluth, PhD, and her daughter.

Written by News & Observer science editor Sarah Avery, the article describes how women are increasing in ranks in biomedical degrees earned while still lagging at the associate professor level and up. This trend was cited specifically for faculty and administrators in basic science departments of medical schools but is widespread in academic science and engineering.

In 2007, I wrote about Andrews becoming the first female dean of a top 10 US medical school and expressed my bewilderment that it took that long. In fact, local attitudes were such that Andrews recalled this recollection in a NEJM article about taking the dean's position:

...it continues to be true that we do not expect women to hold certain positions in society or medicine. Recently, I witnessed firsthand the persistence of such expectations, when my husband, our children, and I went to visit a school in North Carolina where Duke staff members had made an appointment for the family of the new dean of the medical school. As we entered the school, its principal vigorously shook my husband's hand and welcomed him, saying, "You must be the man of the moment." Unfortunately, it is quite understandable that it wouldn't have crossed his mind that I might be the "woman of the moment" instead...

It's always a Good Thing to see science featured on the front page of a region's major newspaper, especially the Sunday edition. And I recognize that it was a nice human interest piece for Mother's Day and you don't want to be a cynic on such a day. So, it's no surprise that the article didn't address the specific challenges that women face of achieving the academic heights of Andrews and Kornbluth.

And I see only one lab coat and no eye protection in the lead photograph.

terrasig Mon, 05/10/2010 - 02:02

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Add this on top of the declining intergenerational rates of education. Hard to compete with the WWII generation, but we're now actually below unity gain.

Usually didn't bring the kids to the lab, but my daughter got really good at photocopying articles in the library on snow days.

Hey Abel! Sarah Avery is a graduate of the Addiction Studies Program. Speaking of which, I need to contact you directly ASAP. My computer crashed Tuesday and I don't have a workable address. The one Duke lists for you bounces back!

Pls email me at srusche@nationalfamilies.org

Many thanks,

Sue

Cytogeneticist Dr. Janet Rowley receives AACR Lifetime Achievement Award

terrasig — Mon, 19 Apr 2010 08:19:00 +0000

Cytogeneticist Dr. Janet Rowley receives AACR Lifetime Achievement Award

The 101st Annual Meeting of my primary professional society, the American Association for Cancer Research (AACR), convened in Washington, DC, on Saturday and will run through Wednesday, April 21. The theme for this year's meeting is "Conquering Cancer Through Discovery Research," and focuses strongly on the translation of discoveries into cancer treatments.

Although the Eyjafjallajökull volcanic dust cloud has delayed many European participants, over 17,000 attendees are expected at the Washington Convention Center where over 6,300 presentations are to be given.

AACR was founded in 1907 by 11 eminent physicians and scientists of their time and while "American" is in the name, AACR is truly an international organization.

Seven years ago, AACR instituted their Lifetime Achievement Award in Cancer Research. This year the award went to one of my heroes of cancer research, Dr. Janet D. Rowley of the University of Chicago. Dr. Rowley is best known for her work in the 1970s on chromosomal abnormalities in human cancer, specifically the translocation that involves the "Philadelphia chromosome" and led to the drug to target protein kinases, imatinib (Gleevec or Glivec).

AACR posted a five-minute interview with Dr. Rowley here and I'll describe some history afterwards.

In 1960, David Hungerford at the Fox Chase Cancer Center and Peter Nowell at the University of Pennsylvania reported in the Journal of the National Cancer Institute that cells from patients with chronic myelogenous leukemia (CML) consistently had a smaller version of chromosome 22.

This short chromosome was called the Philadelphia chromosome after the city in which Penn and Fox Chase are located (as well as the headquarters of AACR).

Rowley advanced this work by examining chromosomes microscopically using a combination of staining techniques (Giemsa and the fluorescent antimalarial drug, quinacrine) to discern that the missing portion of chromosome 22 had been added to the long arm of chromosome 9 in CML patients. Remember that at this time there were no probes for doing fluorescent in situ hybridization (FISH). Rowley relied instead on the unique quinacrine staining patterns that appeared on partly elongated chromosomes generated by brief treatment of patient cells with the microtubule polymerization inhibitor, vinblastine. A figure of this work, published in Nature 1973;243:290-293, is shown here.

Finer techniques later showed that a small portion of chromosome 9 was translocated to chromosome 22 in a reciprocal manner.

Just prior to this work, Rowley had described the (8:21) translocation in acute myelogenous leukemia (AML) then later reported the (14:18) translocation in follicular lymphoma and the (15:17) translocation in acute promyelocytic leukemia (APL). The prevailing wisdom was that chromosomal abnormalities were merely after-effects of transformation but Rowley held that these specific changes could be causative in cancer. When she received the Presidential Medal of Freedom last year, she noted that her ideas were met with "amused tolerance."

Nora Heisterkamp and her colleagues first cloned the t(9;22) breakpoint on chromosome 9 in 1983. She later demonstrated this region encoded an aberrantly regulated c-abl oncogene, a tyrosine kinase, fused with a normal gene that her group proposed naming bcr for "breakpoint cluster region." (The name abl was derived from the viral version in the Abelson murine leukemia virus; hence the long name of the ABL protein is "v-abl Abelson murine leukemia virus oncogene homolog").

Condensing many years of work, the resulting BCR-ABL protein was later shown to cause leukemia in mouse models with the protein activating several pathways regulating cell proliferation while also inhibiting apoptosis. In the late 1980s, imatinib emerged from a chemical library screen for PDGFR and ABL kinase inhibitory activity at Ciba-Geigy, now Novartis. In 1996, Dr. Brian Drucker at the Oregon Health and Science University showed in a series of critical experiments that imatinib (also known then as STI571) selectively killed cells expressing BCL-ABL but not the parental line. The drug entered clinical trials in 1998 and imatinib mesylate (Gleevec/Glivec) was approved by the US FDA in 2001 for the treatment of CML.

This is just one example of the impact of Rowley's original work. Rowley's identification of the (15;17) translocation in APL led to the use of all-trans-retinoic acid against this leukemia. She also demonstrated ten years ago that high levels of maternal ingestion of bioflavonoids could lead to chromosomal breakage and the MLL translocation responsible for infant leukemias. Her work has continued today to understand how breakpoints influence the expression of microRNAs involved in oncogenesis.

In the interview above, Rowley makes several noteworthy points. First, she notes that the Philadelphia chromosome translocation discovery was actually made on her dining room table when she was working part-time, bringing home the micrographs from lab and spreading them out at home. Rowley was noted elsewhere by Nobel laureate and incoming AACR president Elizabeth Blackburn as saying that working part-time actually gave her time to think, as opposed to all of the other activities that come along with a full-time position.

Rowley also mentioned that she made her major discovery at the age of 50. Noting that "we're not like mathematicians," Rowley encouraged young(er) investigators to be patient if things don't go right early on. She also stressed the importance to junior scientists of having a more senior advisor who is truly committed to helping one develop as an independent investigators.

I would have been curious to know if Rowley thought her approach to her career would brought her the same success if she were coming up in the academic ranks today, especially when pursuing a part-time position might be considered not being serious about your science (although I suspect some may have felt that way in the 70s as well).

Dr. Rowley elaborates on her personal story and the impact of her work this 2009 article in Annual Review of Genomics and Human Genetics. I strongly encourage this article to those interested in further reading about Dr. Rowley and chromosomal translocations in leukemias.

terrasig Mon, 04/19/2010 - 04:19

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Interesting. I've heard all kinds of rationalizations from women who were forced to take part-time positions for various reasons.

I think the comment that it's better than working full-time because it gives you time to think just goes to show how broken things are. Scientists should have built-in time to think. And full-time salaries to do it with.

This is why I blog: from rock bottom to top tier

terrasig — Sat, 10 Apr 2010 08:02:19 +0000

This is why I blog: from rock bottom to top tier

Last July we wrote about the 40th anniversary of the Apollo 11 moon landing and spoke of Buzz Aldrin's autobiography about his battle with alcoholism in the years following. The post drew a comment from a reader who I've renamed "Anon."

Thank you so much for this post.

I am a recovering drug addict and am in the process of applying to graduate programs. I have a stellar GPA, have assisted as an undergraduate TA, and have been engaged in research for over a year.

I also have felony and was homeless for 3 years.

I don't hide my recovery from people once I know them, but I sometimes, especially at school, am privy to what people think of addicts when they don't know one is sitting next to them. It scares me to think of how to discuss my past if asked at an admissions interview. Or whether it will keep me from someday working at a university.

I've seen a fair amount of posts on ScienceBlogs concerning mental health issues and academia, but this is the first I've seen concerning humanizing addiction and reminding us that addiction strikes a certain amount of the population regardless of status, family background or intelligence.

I really appreciate this post. Thank you.

Regular readers know that while I am not a substance abuse researcher, many drugs of abuse do come from my research area, natural products. Think cocaine, morphine and other opiates, psilocybin, mescaline, etc.

I also have special compassion for folks with the biochemical predisposition to substance dependence, especially as I come from a long line of alcoholics including my beloved father who I lost way too early.

With that said, I'm sure you understand how Anon's comment hit me and how grateful I was for her appreciation. So moving was her comment in fact that I raised it to its own post. Since many of you readers are in academia and serve on graduate admissions committees, I figured you'd have some good advice for Anon.

Well, you did. Here's the comment thread as a reminder.

And guess what? I got this e-mail from her a couple of days ago.

Hi! Remember me from last fall? You graciously posted a letter I wrote you in response to an article about alcoholism, and I got advice from people about how to go about applying to grad school given my criminal record...forgive me, but I no longer have our previous emails, and so also, your actual name. I apologize!
Well, I wanted to drop you a note and let you know how it all turned out...it went smashingly well. I was accepted at every school I applied to, and I will be attending [Ivy League U] in the fall! I did great, even received a [major fellowship award].

About half of the schools I applied to specifically asked about a criminal record. After reading the comments on your blog around how some schools separate the criminal questions from the remainder of the app, I called each school that asked and inquired about how their process worked. They all separated that section, and it was reviewed by the Deans usually. While I had to provide additional explanation of exactly how I ended up in the position to commit my crimes (homeless and addicted is the easy answer) at one institution, each institution that asked about my record accepted me in the end.

So, exciting days for me! Just thought I'd let you know how it wrapped up...or is just beginning, depending on how it's looked at! By the way, I also recently celebrated 5 years clean. Now, I'm atheist, so my H.P. [Higher Power] doesn't REALLY work like this, but check it out. I received my acceptance letter and offers of full financial support from [Ivy League U] and [another Ivy League U] at the beginning of March. They were both dated March 2. Which is my clean date. Hot damn, ain't life something?!?

Thank you for your help last year, I appreciated it a lot!

Take care!
[Anon]

Hot damn, indeed!

As you might guess, I am beside myself with joy for my dear commenter. I am most encouraged that the system worked in a way that a former addict has been rewarded for busting her ass and getting her life back together.

And even after four years of doing this bloggy thing, I am amazed at the wonderful people we draw here. Yes, yes, the internet is often an ugly place. But this community - I'm talking to you, Dear Reader - put up over 60 comments of advice for Anon at this post on how she might approach the grad school application process and interviews, particularly in having to explain a three-year gap in her work and education history on top of the concern in addressing her criminal record. You gave someone who needed it some very unique insights that I doubt would have been possible before this medium existed.

Wow. Just wow.

So to those of you who dial us up every day: take pride in the assistance you've offered this outstanding and dedicated woman and helped her achieve her dream.

Congratulations, Anon - and thank you, readers.

terrasig Sat, 04/10/2010 - 04:02

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I love this! Love it! This is what I love about the internet.

i got all choked up reading this

Congrats Anon. Best of luck in grad school!

That is FANTASTIC. Best of luck, Anon. Knock 'em dead in grad school!

that is great. congrats! I'll praise the Lord for you! Amen.

Wonderful! It's good to hear about people growing and moving forward and using resources like this community.
Keeps me going to work another week.
Of course, it'll probably help me justify staying up too late online, but, hey, I'm opportunistic.
I heart the internets.

Thank you all!! I also &hearts the internet and the community it can offer! Thank you for your support, advice and encouragement, and I am SO looking forward to grad school...

anon

Congratulations, Anon! Your story (and others like yours) helps to give me back some of my faith in humanity and hope for the future.

I wish you all the best in grad school!

I remember the original comments and posts very well, as they did a great impression on me, and it's great to hear this - congratulations anon.

One of my best students was a former San Quentin inmate (for manslaughter). This man had a huge impact on my whole class (English comp.) by being volunteering often to go over this topic and how he planned to approach the essay structure while the rest of the class remained timidly silent (mostly younger folks). I won't soon forget him, though I do not remember his name. His history: Navy Seal discharged for having asthma; drug addict alcoholic unable to deal with life beyond being a Navy Seal; bouncer at a bar where he killed a patron; San Quentin inmate; over-the-road trucker paralyzed from the waist down in a tragic accident; father, husband, grandfather; best community college student ever. Even introduced me to Billie Holiday's "Strange Fruit," which I played to each class over subsequent semesters. To all of you out there with struggles, I say, "Keep on keeping on." You'll get there. And who knows who you'll impact for the better, once you turn your life to the better.

This made me smile.

A lot.

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

terrasig — Tue, 16 Mar 2010 21:02:43 +0000

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

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
Ted 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.

A native of Chicago, Dr. Puck did both his undergraduate (1937) and graduate training (1940) at the University of Chicago. His doctoral mentor in Physical Chemistry was Dr. James Franck, a physicist who had shared the 1925 Nobel Prize in Physics. Puck's PhD work focused on the atomic transitions in chlorophyll necessary for photosynthesis.

At the end of his PhD, World War II had begun and Puck remained at Chicago as a research associate to work with Dr. O.H. Robertson on the potential of polyethylene vapor to kill airborne microorganisms for the Commission on Airborne Infections of the Office of the Surgeon General of the Army. The relevance of this project during wartime was exemplified by Puck publishing five papers in Science and six papers in J Exp Med on this work. While on this project, he worked with Phil Marcus, a master's student who would later join him in Colorado.

After the war, Puck did formal postdoctoral work on the genetics and kinetics of bacteriophage interactions with bacteria at the California Institute of Technology with Max Delbrück, who later shared the 1969 Nobel Prize in Physiology or Medicine with Alfred Hershey and Salvador Luria (yes, Luria broth). Delbrück was originally a physicist and obviously contributed to Puck's early enthusiasm for "applying physicochemical approaches to problems of biology."

Clonal populations of mammalian cells
Puck's work with phage impressed upon him that studying human genetics would require that similar techniques be developed to manipulate human cells. Because HeLa cells were taken from the tumor of Henrietta Lacks, they contained several populations of cancer cells. Puck and his then-graduate student Phil Marcus and Steven Cieciura were trying to figure out how to grow clonal populations from single cells.

Establishing "clones," or colonies that grew from a single cell, was first accomplished with mouse L929 cells in 1948 by Katherine Sanford and Gwendolyn Likely in the laboratory of Wilton Earle at the National Cancer Institute (JNCI 1948; 9:229). Earle is credited with the isolation and propagation of the first continuously cultured cell line, mouse L cells. This heterogeneous population was originally isolated in October 1940 as an outgrowth of subcutaneous connective tissue from mammary fat pads excised from a 100-day-old C3H/An mouse (JNCI 1943: 4:165). The cells acquired a malignant phenotype in culture and could produce sarcomas when injected back into mice.

Just as an aside, Earle's group acknowledged the cell culture work of Lewis (Science 1935; 81:545) and Fischer and Davidsohn (Nature 1939; 143:436). The 1935 paper from Warren H. Lewis was his presidential address to the American Association of Anatomists where he reported the continuous culture of rat sarcoma cells for 2-4 years, although no photographs or formal data were shown. Albert Fischer and Fanja Davidsohn reported carrying mouse adenocarcinoma cells for up to 12 years. But while both Lewis and Fischer had lengthy careers, I'm unable to find any follow-up literature on these respective cell lines. Hence, the most continually documented work of Earle's group is most deserving of the "first" designation.

Recognizing that L cells came from a heterogeneous cell population, the Earle group worked on isolating single cells and propagating clonal cultures from those cells. At the time, the composition of cell culture medium was not fully refined and attempts at growing out cells from small populations were unsuccessful. Earle's group recognized that using medium "conditioned" by growing cells produced diffusible factors that encouraged growth of small cell populations. To produce single clones, Earle's group painstakingly transferred single L cells to small capillary tubes together with a small amount of conditioned medium, producing the first clonal cultures of immortalized mammalian cells. The most widely studied of these is clone 929, known more properly as NCTC L-929 cells, the first immortal mammalian cell line offered by ATCC, appropriately as CCL-1.

The capillary approach to cloning seemed too cumbersome to Puck and he wanted to develop a method that was more analogous to isolating clonal bacteria cultures from distinct colonies that had grown from individual cells. Moreover, quantitative assessment of cellular sensitivity to drugs or radiation would not be possible using the capillary method. Because he was interested in human genetics, he decided to work with HeLa cells. As cited below in references 1 and 2, he obtained his original HeLa culture from the George Washington Carver Foundation of historically black institution, Tuskegee University in Alabama, rather than from George Gey at Hopkins who had originally isolated the cells.

From Hopkins to Minnesota to Alabama to Colorado
The role of Tuskegee in the polio treatment and vaccination effort is an engaging story in its own right that is told by Rebecca Skloot in her book and worthy of expanding into its own separate post. The National Foundation for Infantile Paralysis (NFIP), known today as the March of Dimes, had funded a HeLa mass production laboratory at Tuskegee to provide a uniform source of cells in tests of the Salk polio vaccine after having had established a hospital there in the late 1930s to care for black polio victims.

William Scherer and Jerome Syverton at the University of Minnesota (together with Gey) had shown that HeLa cells could be infected with all three strains of the poliomyelitis virus circulating at the time which could then be neutralized by incubation with antibodies to the virus (J Exp Med 1953; 97:695). To test the efficacy of the vaccine, 23 sites around the country were charged with taking post-vaccine blood samples from over 2 million children to test the ability of their serum to neutralize the virus in culture as an indication of antibody titer. The Carver Foundation at Tuskegee supplied these cells, but also provided samples to researchers such as Puck. When starting the production facility, Tuskegee scientists Russell W. Brown and James H.M. Henderson traveled to the laboratory Scherer and Syverton at Minnesota to learn HeLa culturing techniques. Scherer was one of the first recipients of HeLa cells from George Gey and in fact had maintained an original culture, something Gey himself had not. So, when ATCC later asked Gey to submit a culture for the repository, Gey had to solicit Scherer. When you look up the original HeLa culture (CCL-2) at ATCC, you will see that Scherer, not Gey, was the submitter.

Clonal isolation of HeLa S3
Puck hypothesized that a highly conditioned medium could be produced by a monolayer of cells that had been rendered incapable to dividing by irradiation. By providing conditioned medium in a large vessel capable of supporting colony growth, it would be easier to quantify the efficiency with which clones were produced while optimizing media composition. He defined such replication-incompetent cells as "feeder layers." In initial experiments with postdoctoral fellow Dr. Roshan Christensen, they attempted UV radiation but it was insufficient to damage the cellular DNA. They were about to move on to X-rays when Christensen became pregnant. She and Puck made the decision that use of X-rays was not in the best interest of her baby and she moved on to other projects until the next person joined the lab.

That next person was Phil Marcus, the MS research associate Puck had known from the University of Chicago. Marcus was recruited by Puck with the intention of having him join the new PhD program at Colorado once he met the course requirements. Around the same time, famed atomic physicist Leó Szilárd was visiting Puck's lab to learn about molecular biology. This is the same Szilárd whose work with Enrico Fermi on the Manhattan Project led to the atomic bomb. As Puck noted in his autobiography, Szilárd began involving himself in the project without advance discussion, instead talking privately with Marcus.

Initially, Puck had wanted the feeder layer to be irradiated and new HeLa cells plated on top of them to grow into colonies in empty spaces on the Petri dish. Szilárd appears to have understood that the feeder layer was necessary but had not known of the idea to irradiate the cells. Therefore, he suggested privately to Marcus that he construct a glass slide platform above a freely growing feeder layer on which single HeLa cells would be plated. Over the course of time, hard feelings developed between the young professor and the senior scientist. The ultimate outcome, however, was the combination of the two ideas: Szilárd's platform above Puck's irradiated HeLa feeder layer.

The drawing above comes from a 1955 PNAS paper by Puck and Marcus (1) where Szilárd's contribution is noted in the acknowledgments. The irradiated feeder layer of cells is at the bottom. The microscope slide showing the colonies generated was originally prepared by plating a dilute suspension of HeLa cells containing only 5 to 100. The cells were allowed to attach to the slide for 5 hours, then placed in the media with the irradiated feeder layer. After 8-10 days of incubation, colonies of 800-2,000 cells grew out from the original plated cells.

But how to harvest the clones? In a subsequent 1956 paper in the Journal of Experimental Medicine (2) Puck, Marcus, and Steven Cieciura describe the use of trypsin to harvest the colonies using what we today call cloning rings. Here is the original text:

This single passage is notable in that it describes not only clonal isolation and propagation of cells but establishes the basis for clonogenic assays of cancer cells (a measure of a given cell's ability to replicate into colonies) and also the more stringent soft-agar assay which measures a cell's ability to form three-dimensional colonies.

And finally after three blogposts, we learn what HeLa S3 cells are: they were the third clone isolated and propagated from the heterogeneous HeLa culture with the letter S in honor of Dr. Florence Rena Sabin, for whom the building housing Puck's new laboratory was named in December, 1951.

Why S3 and not S1 or S238?
But I couldn't stop there. I wanted to know why Puck continued working with the S3 clone and why that is the one deposited with ATCC and sold as CCL-2.2.

Puck's laboratory continued this work in an attempt to better define media components necessary for growing these cells at high clonogenic or "plating" efficiency. First Puck and Harold Fisher followed the observation that HeLa S1 cells formed smaller colonies that HeLa S3 cells grown for the same number of days. In their 1956 J Exp Med paper (3), they demonstrated below that in the absence of a feeder layer, the S3 clone could still form colonies at very low concentrations of human serum used in the growth medium. (By the way, the human serum was also provided by the Carver Foundation at Tuskegee from who paid local donors with funds from the NFIP contract - we know today that HeLa cells can be grown with fetal calf serum instead).

We know today that the feeder layer "conditioned" the media with peptide growth factors but there were also some important biochemicals they provided that were missing from the media used at the time. In their 1957 Science paper (4), Gordon Sato, Fisher, and Puck showed that HeLa S3 cells required inositol to form colonies in the absence of a feeder layer but were inositol-independent when a feeder layer was present. In other experiments, they showed that the HeLa S3 cells also required cholesterol.

But when they analyzed the series of S clones for their requirements across the board, the S3 clone was the most hardy and grew with the highest plating efficiency under optimized condition. The authors also noted that the S3 phenotype seemed to be the most predominant in the original heterogeneous HeLa cell population.

Today, as we have gone away from the use of high concentrations of human serum toward low(er) concentrations of fetal calf serum, I wonder if mixed HeLa cultures still contain the less robust S1 cells. As I said in an earlier post, the HeLa S3 cells look more compact and uniform than most HeLa cultures I have worked with. But these have been carried separately under varied conditions over the course of decades. So, your choice of HeLa or HeLa S3 cells for your work may be one more of semantics than practicality.

I welcome comments from others who may have personal lab experience with either cell population.

What was so special about HeLa cells?
I know that Rebecca Skloot has gotten this question ad nauseum while on her book tour. It is the obvious question: what about HeLa cells made them the first continuously culturable human cell line out of the hundreds of tumor specimens that came from Johns Hopkins surgical wards and into the laboratory of George Gey?

I thought more about this while reading this old papers. We know today that HeLa cell DNA contains portions of a human papillomavirus genome and it overexpresses telomerase, both mechanisms by which normal cells can be transformed. But many cells are virally-transformed and many more overexpress telomerase. And even though HeLa cells are billed as growing rapidly, their 24 hr doubling time is shared by a great many tumor cell lines.

Instead, I think that the tumor cells from Ms. Henrietta Lacks were somehow capable of tolerating the incomplete nutritional conditions of the cell culture media used in the early 1950s. We know from Puck's work that the cells grow optimally in the presence of inositol and cholesterol but other cell lines have much more stringent requirements for non-essential amino acids, substrates for oxidative phosphorylation, and only tolerate very narrow ranges of pH. I've not conducted any formal comparative investigations but I think that Henrietta Lacks's tumor cells were so aberrant that they had minimal nutritional requirements relative to cells from other tumors that made it to the Gey laboratory.

This, I suspect, is also why Ms. Lacks's cancer was so unique and voracious as described by the pathologist at that time. It grew at metastatic sites that may have been suboptimal in terms of availability of biochemicals and maybe even tolerated hypoxia and/or acidic pH better than other cervical cancers. I know that many labs have new students first try their hand at culturing HeLa cells because they are hardy and forgiving of bad technique.

Perhaps what makes HeLa cells so easy to culture are the same reasons that made them so deadly to Ms. Lacks.

I have more to say about Dr. Ted Puck because he was truly a remarkable scientist and gentleman. He made many other contributions in his 50+ year career and I'd like to share that with you in another post.

But now you know the difference between HeLa and HeLa S3.

References:
(1) Puck TT and Marcus PI (1955). A rapid method for viable cell titration and clone production with HeLa cells in tissue culture: the use of X-irradiated cells to supply conditioning factors Proceedings of the National Academy of Sciences, 41 (7), 432-437 DOI: 10.1073/pnas.41.7.432

(2) Puck TT, Marcus PI, and Cieciura SJ (1956). Clonal growth of mammalian cells in vitro: growth characteristics of colonies from single HeLa cells with and without a "feeder" layer Journal of Experimental Medicine, 103 (2), 273-284 DOI: 10.1084/jem.103.2.273

(3) Puck TT and Fisher HW (1956). Genetics of somatic mammalian cells: I. Demonstration of the existence of mutants with different growth requirements in a human cancer cell strain HeLa Journal of Experimental Medicine, 104 (3), 427-434 DOI: 10.1084/jem.104.3.427

(4) Sato G, Fisher HW, and Puck TT (1957). Molecular growth requirements of single mammalian cells Science, 126 (3280), 961-964 DOI: 10.1126/science.126.3280.961

terrasig Tue, 03/16/2010 - 17:02

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please consider submitting your post(s) about Dr Sabin to the Diversity in Science carnival for March, celebrating women's history month.

Hela cells were not the first to be immortalized in culture. Read hayflicks letter to science for details(latest issue).

Should the title say Ted Puck, PhD?

@DNLee - Hello and congratulations to the newly-minted Dr. Lee!!! Yes, indeed, I'll submit the previous post to the Diversity in Science Carnival for Women's History Month.

@Canada - I believe that you are referring to a letter from Dr. Hayflick to Nature about Steve Silberman's review of The Immortal Life of Henrietta Lacks. Mr. Silberman simply left out the word "human" from his description of HeLa as the first immortal line.

As Dr. Hayflick pointed out, and as I wrote about extensively above, the first immortal cell line was the mouse L cell line isolated by Wilton Earle in late 1940, published in 1943.

@MitoScientist - Yes, you are correct. I will make the change to PhD in the title. Thanks for catching that.

Many, many thanks for reminding me of the origin of the cells which I have worked with daily for over 30 years. Very well done.

For the record, I didn't leave anything out of my Nature review of Skloot's wonderful book. The Nature editors left the word "human" out of the subhead, that's all.

Thank you Professor Racaniello for your kind words. Your work on books, podcasts, and other outreach is an inspiration to me - I've learned a great deal of virology from you and use some of your materials in my classes. It was a delight to go back and read some of these old papers and think what it was like to do this work at the time.

Steve, that's a very good point, one that all readers should note. While I have the luxury of titling my posts whatever I want, print writers are generally at the mercy of editors when titles are selected for their articles.

So, I stand corrected on my comment above - Mr. Silberman did not leave out "human." The editor did. I hope that information makes its way back to Dr. Hayflick.

I thoroughly enjoyed this series and am glad that others are speaking out for the researchers who developed cell culturing. I was thrilled to hear that Howard Jones is still with us. His wife and he were legends when I arrived in Baltimore in the early seventies.

I believe that the biography of Henrietta Lacks painted some of the same generation poorly.

I'm not a scientist, working in IT myself. Stumbled upon a display of HeLa cells in the Exploratorium in San Francisco couple of months ago. Was interviewed on site by a lady researcher about the effectiveness and usefulness of the display, too.

I vaguely remembered reading something about these cells years ago, and that display kindled my interest again. So have been following these articles with much interest.

Amazing details, and lots of new names for me to explore and read about.

Well done.

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

terrasig — Sun, 07 Mar 2010 11:02:34 +0000

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."

Florence 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."

Unfortunately, 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.

What 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.

A career of "firsts"
At Johns Hopkins, Sabin worked with anatomist Franklin Paine Mall and published in 1901, the year after her graduation, An Atlas of the Medulla and Midbrain, that served as an neuroanatomy text for the next three decades (see here at Google Books). Her 1900-01 internship with famed physician Sir William Osler is credited with planting the seed of her interest in tuberculosis that came back to serve her in the laboratory in the 20s and 30s and in public health in the 40s.

In 1903, Sabin became the first woman faculty member at the Johns Hopkins School of Medicine and was noted for her work on the origin and development of the lymphatic system. Her 1913 book arguing that lymphatics derive from the venous system and not tissues spaces is probably the most complete compilation of the nine critical publications documenting her early work, also accessible here at Google Books. In 1917, she was appointed Professor of Histology, the first woman full professor at Johns Hopkins and in 1924 became the first woman president of the American Association of Anatomists.

But when Mall died in 1917, Sabin was passed over as head of the anatomy department in favor of her own former student, Dr. Lewis Weed. She continued in her work but, not surprisingly, was ripe for recruitment to Rockefeller Institute for Medical Research by Dr. Simon Flexner, the original director of Rockefeller and elder brother of Alexander Flexner. (Discussed here in a 2006 NEJM review, Alexander Flexner's 1910 report defined the standards of American and Canadian medical schools for the rest of the 20th century.)

In joining Rockefeller as a full member, a full professor equivalent, Sabin was the first woman to hold such a position at that institution as well. Her work had turned to the immune system's response to the bacillus that causes tuberculosis, monocytes in particular, and how fibrotic "tubercles" develop and contribute to the destruction of surrounding tissue. In April, 1925, Sabin became the first woman elected to the National Academy of Sciences. This link will take you to a PDF of her notification letter from The Florence Rena Sabin Papers.

Accounts of her time at Rockefeller indicate that she was a tireless mentor of young investigators, men and women, and life in New York City fed her diverse interests in theatre and music. This 1941 version of her personal bookplate reflects her literary interests, work ethic, and love for science. Her National Academy biography notes this comment from a co-worker at the time:

"The great joy and pleasure which she derived from her work were like a contagion among those around her so that all were stimulated in much the same manner that she was. I have never known any other person to be quite so buoyed up by intellectual stimuli as she was. Dr. Sabin was one of those people who, however strenuous the previous day might have been, waked at the crack of dawn with great enthusiasm for what the day was to hold. She was nearly always the first one at the laboratory, and greeted every one with a joie de vivre which started the day pleasantly for all of us. . . . Despite the fact that she was the first to arrive in the morning, she was often the last to leave in the evening."

Photos: Above: Dr. Sabin with her Rockefeller laboratory group in 1930; Below: At her scope, The Rockefeller Archives

"Retirement" on the Health Committee of Colorado's Post-War Planning Committee
When she retired from Rockefeller in 1938, the signature book for her retirement reception (here) reflected the deep admiration her students and colleagues felt for her, including a pre-World War II version of a smiley emoticon from Thomas Rivlin and the inscription, "All blood cells love you and wish you many more happy years." Other inscriptions include, "with ten years of memories that are with each succeeding year more deeply significant, " and another that noted her work in the women's suffrage movement: "with appreciation and admiration of the National Women's Party."

At age 67, Dr. Sabin returned to Denver to live with her sister, Mary, living another career in "retirement." This photo with Mary on the left was taken in 1939, shortly after Florence returned to Denver. (For those of you who know Denver, Florence and Mary lived in the Stanley Arms apartments at 1321-1333 E 10th Ave, just west of Cheesman Park and the Denver Botanic Gardens)

After living in Baltimore and New York City and working at the nation's top medical centers, Sabin was appalled at the state of public health in her native Colorado. As World War II drew to a close, she was tapped by Gov. John Vivian (and then under the next governor) to lead a group examining health services in anticipation of the needs of returning soldiers. A PDF of the letter of invitation can be viewed here.

She traveled to all 63 Colorado counties and lobbied politicians to gain passage in 1947 of four of six proposed "Sabin Bills" to improve preventative health and facilities for existing tuberculosis patients, general sanitation, and an overhaul of the state's Board of Health. She then served on the board of what is now Denver General Hospital and then the Denver Department of Health.

As an example of her impact, Sabin's encouragement of chest X-ray screening resulted in a 50% reduction in the death rate from tuberculosis in Denver within two years. The incidence of syphilis dropped by 90% during the same time period (from 700 to 60 cases per 100,000). In 1951, Sabin received a Lasker Award, not for her laboratory career but instead for her work in public health.

Sabin turned 80 on November 9, 1951, just one month after a woman named Henrietta Lacks had died of cervical cancer at the hospital where she had been a professor. On December 1, the University of Colorado School of Medicine honored Dr. Sabin on this milestone with the formal dedication of the Florence R. Sabin Building for Research in Cellular Biology, the site where the black tobacco farmer and medical research would become intertwined.

On October 3, 1953, Sabin died of a heart attack while recovering from pneumonia at her Denver apartment. Her biography notes that she died while watching her beloved Brooklyn Dodgers on television in the World Series. I find it noteworthy that today a handwritten letter from Dr. Sabin goes for $1,800 whereas a photo signed by 11 members of the 1953 Dodgers can be had for $375.

The story of Florence Rena Sabin is still recognized and examined in pockets of the academy as evidenced by this 2009 article in Gender Forum, an internet journal for gender studies. Entitled. "The Quiet Feminism of Dr. Florence Sabin: Helping Women Achieve in Science and Medicine," by Dr. Patricia J.F. Rosof of St. Francis College, this detailed and painstakingly referenced historical perspective documents Sabin's semi-stealth activism in women's rights extending back to her 1900 graduation from Johns Hopkins Medical School.

A statue of Sabin at her microscope was presented in 1959 as the first of Colorado's representatives in The National Statuary Hall Collection at the U.S. Capitol. Each state is granted only two statues to honor the persons most notable in their history. The other Colorado statuary representative is that of the Apollo 13 astronaut, John L. "Jack" Swigert, Jr., the Denver native who was portrayed by Kevin Bacon in the movie, Apollo 13.

Back to the story of HeLa S3
At the time of Dr. Sabin's death, a physician-scientist named Theodore "Ted" Puck was working on cellular genetics in his University of Colorado School of Medicine laboratory in the building carrying Sabin's name. Recruited to Colorado in 1948 as the founding chair of the Department of Biophysics, Puck played a major role in the application of bacterial culture methodologies to assessing the growth requirements of human cells in culture.

On page 100 of Rebecca Skloot's book, The Immortal Life of Henrietta Lacks, she makes a very brief reference to the role of Colorado scientists in isolating and expanding the first clonal populations of human tumor cells. In the research building named in honor of Dr. Sabin, Ted Puck and his graduate students selected these clones from the mixed culture of HeLa cells. These are the cells that had been circulating amongst researchers for five or six years since first expanded from Mrs. Lacks's tumor in 1951 by technician Mary Kubicek in the laboratory of Dr. George Gey at Johns Hopkins.

In the next post of this series, we'll discuss how Puck and his graduate students provided this immortal link between Dr. Sabin and Henrietta Lacks.

terrasig Sun, 03/07/2010 - 06:02

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Awesome post, holmes! BTW, the Flexner Report was written by Abraham Flexner, not Alexander.

Thanks, brudda, for the compliment and the correction. I can't tell you how many similar mistakes I caught before I hit "publish." I knew it was Abraham, read the NEJM review and saw Abraham, and still wrote Alexander.

Old age, dude. I'm getting old.

Thank you for this.

I'm ashamed to say, I'm from Colorado, and yet I never knew who Dr. Sabin was, or any of this story. This enlightenment is late, but I'm glad of it.

Great, great post, Abel. Makes ya' think about all the potential talent that went untapped because of this ignorance. Yeesh!!

Wonderful history. Can't wait for the next installment.

@Luna - no worries, I didn't know the whole story until I started looking at the original papers on these cells and then read up on Dr. Sabin. I think it's because it was more than one generation before us and people who knew her weren't around when we came up.

@scribbler50 - always great to hear from you, good sir! At least there were some forward-thinking women with the financial wherewithal to make a difference for some.

@Pascale - thanks, doc! I hope to get the rest of this up on Wednesday.

As a Baltimorian, it is very strange to me to read about the actions of people like Gilman and Garret, who I knew only as people for whom private schools and buildings at private schools were named. (Gilman is one of the major boy's private schools, and Garret is a founder of the Bryn Mawr School for girls, where they still take Latin.)

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

terrasig — Sat, 06 Mar 2010 10:40:44 +0000

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

When 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, â¥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.

So 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 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

terrasig Sat, 03/06/2010 - 05:40

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Great hook. I'll be back for the complete story.

I look forward to the next installment!

You fucker! How can you leave us hanging like that?

Don't worry, CPP, you won't have to go looking up 1950s papers yourself. I've just been working on this post in fits and starts throughout LungMutiny2010 and it got too long even when I tried to abbreviate it.

Thanks Carpus and Jaime. Hope the rest hold your interest.

I'll be waiting with impatience, myself....

more! more!

Just cruel. I'm with PP.

Nice intro. I'll be watching for the rest of this story. I've always loved narratives that combine the history with the science.

You may be interested in the following article:
Capes-Davis A et al. (2010): Check your cultures! A list of cross-contaminated or misidentified cell lines. Int J Cancer. 2010 Feb 8 [Epub ahead of print]

[...], we have compiled a list of known cross-contaminated cell lines. The list currently contains 360 cell lines, drawn from 68 references. Most contaminants arise within the same species, with HeLa still the most frequently encountered (29%, 106/360) among human cell lines

Fabulous post -- I hope you continue. And, please, if the rest is as good, turn it into a book. Immortal Life might be a well-written book, and Henrietta Lacks may have been a good & worthy person, but a person of science she was not. All the attention on the person whose cells have been studied only shows the confusion of our society about what's important. It's the Florence Sabins who we need to know more about. A delightful intro for that subject here if you ask me.

@Luna, BioE, Pascale, chezjake - thank you and I hope you'll now move on to Part II here. I'm just realizing it's a rather long post that I could have broken up even more. Part III will go up Monday and will describe the clonal isolation of HeLa S3. It's actually been a lot of fun putting this together.

@sparc - Yes, HeLa contamination is everywhere, still. Thanks so much for the heads-up on this latest paper.

@Albion - I'm glad you enjoy the post but please do take the time to read the Immortal Life. The author interspersed the family stories with some quite detailed chapters on the science and the stories behind the scientists. These chapters are well-annotated with the original literature as well, something you don't see in many books.