Terra Sigillata

Sustained interest in K2 Spice, JWH-018, and related currently-legal cannabimimetic products

Tue, 25 May 2010 11:02:27 -0500

Just a quick post this morning as I am performing my professional responsibility to our nation's health research agency.

In yesterday's issue of USA Today (which I only read on the iPhone app or when staying at a hotel that gives it to us free), Donna Leinwand wrote about a currently legal substitute for marijuana called by various names such as K2, Spice, Black Mamba.

Nearly a dozen states and several cities are banning or debating bans on K2 -- a packet of herbs coated with a synthetic chemical that mimics a marijuana high when it's smoked -- amid fears that its use is spreading among young people.

Each of these products is comprised of a generic plant material fortified with one of more marijuana mimics, or cannabimimetics, originally synthesized in the 1990s by Clemson University organic chemist John W. Huffman and his graduate students. These compounds generally go by JWH followed by the lab's code number for the compound. The most popular of these is JWH-018.

These compounds are not considered cannabinoids since they are synthetic and do not bear obvious structural similarity to Δ⁹THC or other naturally-occurring cannabinoids. However, these compounds do bind cannabinoid receptors in the brain and appear to produce psychoactive effects similar to that of marijuana. Descriptions of various K2 Spice products, and now pure JWH compounds that have become available, are richly described by our commenters to the February post. In fact, a comment received this week, speaks of the risks of the variable levels of JWH compounds that might be sprayed on different products.

The primary driver of K2 use appear to be by cannabis enthusiasts who are either on probation or otherwise subject to urinary drug screening tests that detect THC but not (yet) the JWH compounds. Others simply wish to purchase a still-legal high rather than risk the variable ire of law enforcement officials around the US.

For much more on the pharmacology and risks of dependence on K2 or pure JWH-018, you can read two posts written under the ScienceBlogs masthead in February, one by me and one by my blog brother, DrugMonkey.

Brother Drug and I have been completely blown away by the sustained interest in each of our posts that has actually grown over the last 100 days. In both of our cases, approximately 50% of our readership lands on our February K2 posts. Perhaps this is no surprise given that each of our posts show up at the top, or at least the first page, of Google search results for "K2 Spice." On top of this, I was the beneficiary yesterday of Reddit member Travesura who recommended his followers to us with the teaser:

"Heard of that "K2 Spice" that everyone has their shorts in a wad over? Here is the best explanation that I have seen about what it is, and how it works."

Thanks to Travesura and the timeliness of Leinwand's USA Today article, our February K2 Spice was the landing site of 2,853 of our last 4,000 visitors.

Holy moly.

But I learned possibly of another trend: we received a fair number of hits yesterday from various US military IP addresses, some coming via search terms involving detection of JWH-018.

For our military readers, has any directive come down the pike that soldiers will now be screened for JWH-018 use? Or is this just a coincidence?

But I still have no explanation as to why both DrugMonkey and I are getting such sustained interest in this topic, even more than for previous posts that had short-term high readership such as herbal products adulterated with erectile dysfunction drugs and the Evolv water/M.D. Anderson kerfuffle.

Update: The always-excellent Erowid site has information on the approach to K2 Spice by the US military. The US Army has banned the substance and this January 23, 2010 article by Hope Hodge at the Jacksonville (NC) Daily News on the possible discharge of two Marines at Camp Lejune:

Marine Corps officials did not immediately respond to queries about working policies surrounding spice or how Marines aboard Camp Lejeune are briefed about it. Base officials said that, in place of specific guidance, the use of spice is illegal under SecNav Instruction 5300.28d and OpNav Instruction 5350.4c, which broadly regard substance abuse prevention and control.

Hodge followed up on February 5 with a report that the US Marines has issued a ban of 10 substances that include Spice and Salvia divinorum, the source of the disturbing hallucinogen, salvinorin A.

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

Sun, 23 May 2010 10:45:02 -0500

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.

What do we call the Law & Order "Immortal" rip-off of the HeLa story?

Thu, 20 May 2010 22:36:51 -0500

So I came home the other night to PharmGirl and PharmKid watching wide-eyed and jaw-dropped at an episode of NBC's Law & Order program's that seemed to be a thinly-veiled adaptation of the story of Henrietta Lacks and her family as written in Rebecca Skloot's best-selling book, The Immortal Life of Henrietta Lacks.

The story in the Law & Order "Immortal" episode bore striking similarity to the HeLa cell story, one of a Black woman whose cancerous tumor samples were taken without her consent that were then used widely for scientific discovery.

By thinly-veiled, I mean that the episode was entitled "Immortal" and used the example of a Black man whose lung cancer cells were taken without his knowledge - Nathan Robinson and the cell line name NaRo - and used by a company called Hema Labs. Some very personal details bore close resemblance to the HeLa story: a son who committed murder, a daughter institutionalized.

By "rip-off" - well - I'm unable to find a complete transcript of this Law & Order episode but a 7-minute clip can be seen here at the show's website.

My wife had at first thought that Skloot and/or the Lacks family had provided screenplay or background guidance on the episode. However, this was not the case at all as she carefully watched the credits.

Perhaps most ironic is that the episode pontificated about how the family of the cell's donor had been taken advantage of, never compensated properly, and that justice must be served to end the legacy of exploitation of the fictional family.

The story of Henrietta Lacks had been told formally in fits and starts since Michael Gold's 1986 book, A Conspiracy of Cells, and a 1997 BBC documentary. A Law & Order episode on such a topic might have been aired anytime since the series debuted in 1990. Law & Order has advertised that their shows are "ripped from the headlines" but I don't believe I've ever seen such an episode adapted in coincidence with the publicity and release of a best-selling book.

June Thomas wrote of this convergence in Slate's culture blog, Brow Beat:

Even after 20 seasons of watching Law & Order and a year of chronicling the headlines that inspire the show's story lines, I can't recall an episode where ripped was quite so appropriate. Many of the particulars of the NaRo storyline were shockingly close to the true story. For instance, Nathan was buried in an unmarked grave at the Robinson family homestead, while Henrietta Lacks was buried in an unmarked grave in Clover, Va., where she grew up. One of Nathan Robinson's children lived in a care facility, as did one of Henrietta Lacks' daughters.

Over the years, the medical establishment sometimes claimed that the HeLa cells came from a woman called Helen Larsen or Helen Lane--a practice that robbed Henrietta Lacks of the fame and respect she deserved. It's ironic that her contribution has now been obscured one more time. The fictional prosecutors secured a payment to the fictional Robinson family--perhaps the producers of Law & Order should make a donation to the Henrietta Lacks Foundation. (Skloot is donating a portion of her book's proceeds to the foundation.)

(Disclosure: I have been asked to serve on the Board for The Henrietta Lacks Foundation as a result of my background in higher education and scholarship support of underrepresented groups).

I don't think that anyone would disagree that what Law & Order did was slimy. The Lacks family members only grew to trust Skloot over the ten years it took to develop the book on the condition that she tell the story fully and truthfully, letting the world know what their matriarch's unwitting gift had done for humanity and how the family was further exploited in the process. Skloot's vision has always been one to do something substantive for the family and to create a mechanism for other scientists and beneficiaries of HeLa cells to show their gratitude to the Lacks family.

I'm not a lawyer or publishing industry expert but this incident has gotten me thinking about where the line might be drawn between telling a story and doing something wrong. We see this all the time in music, for example, where riffs are taken from some songs and used in others in a different context. How much is a thematic adaptation and, in many cases, a tribute to the original composer, or subconscious copying such as in George Harrison's "My Sweet Lord" and The Chiffons' "He's So Fine."

As I understand from screenwriter John August's blog, the common movie and television disclaimer - "The events depicted in this show/movie are fictitious. Any similarity to any person living or dead is merely coincidental" - is primarily there to absolve a studio of libel or defamation of anyone living or dead. I don't believe it absolves one of intellectual property infringement. Entertainment law expert Mark Litwack offers his own opinions on what is required to write about life stories for the little or big screen - of course, his opinions carry their own disclaimer.

I'll be interested to learn what others think who know more about entertainment and publishing law or from anyone who deals in issues of thematic inspiration vs. actual copyright infringement.

(P.S. I might also add that what ADA Cutter did to Lt. Van Buren beginning at 4:37 of the clip at the website was also unconscionable - I love S. Ephatha Merkerson - her character, by the way, is a Black woman with cervical cancer just like Henrietta Lacks.).

This post is written as a personal, individual opinion and is not in any way an official statement of the Board of The Henrietta Lacks Foundation.

Agility of the community college system in preparing for BP oil spill landfall

Wed, 19 May 2010 11:02:56 -0500

The leadership team and all the staff here at Terra Sigillata world headquarters was taken aback yesterday when reports surfaced about the appearance of tar balls on the beach at Fort Zachary Taylor State Park and Bahia Honda State Park, the closest long beach to Key West, Florida. A Coast Guard marine laboratory in Connecticut is currently examining the content of the tar balls to determine if they are indeed from, as feared, the BP Deepwater Horizon well. (Someone in the field has to help me out here but I believe there are an awful lot of LC/tandem mass spectrometers at Florida's institutions of higher education and research institutes.).

We have spoken previously of our education and research work with colleagues at the Key West Tropical Forest & Botanical Garden together with Duke University conservation biologist, Stuart Pimm. This area holds great personal and professional meaning for us here. The apparent spread of the oil spill not only means that the Gulf Coast from Louisiana to the west coast of Florida will be affected but that oil may begin to find its way up the Atlantic coast. Not that any place is more or less important or environmentally sensitive, but the long range effects of the spill may be coming to realization.

We keep a subscription to Key West's The Citizen newspaper and I've been really impressed by how active the community has been in mobilizing for combating the spill. The maps and current profiles I see remind me of those we see when a hurricane is approaching. As such, Florida Keys Community College has launched today one of two planned, three-day training sessions for responding to volunteer to help mitigate damage from the spill. The $575 tuition also certifies one to meet OSHA requirements for Hazardous Material Technician.

24-Hour OSHA HAZWOPER (Hazardous Waste Operations and Emergency Response Standard) Technician Level Training:

Wednesday May 19 - Friday May 24
8:00a.m.-5:00p.m. at FKCC's Key West campus
Cost: $575/person

Monday May 24 - Wednesday May 26
8:00a.m.-5:00p.m. at FKCC's Key West campus
Cost: $575/person

Description: The 24-hour course is designed for persons who respond to a hazardous materials incident for the purpose of stopping, containing, controlling and cleaning up the release. This level of training is also appropriate for persons performing limited tasks at an uncontrolled hazardous waste site and who are unlikely to be exposed above permissible exposure limits. This training meets all OSHA requirements for the Hazardous Material Technician (29 CFR 1910.120).

Please note: Those who have received the 4-hour Marine Oil Spill Cleanup course will be dismissed at 12:00p.m. on the last day of class.

For more information or to register, contact FKCC Director of Continuing Education Cathy Torres at 305-809-3250.

Not written in the workshop description is the likelihood that such training would place one at the top of the list should federally-funded employment become available for cleanup efforts as happened following the Exxon Valdez spill in Prince William Sound in Alaska.

I applaud my colleagues across the Lower Keys and at Key West Community College for mobilizing so quickly and providing timely education to serve the community. We take our community colleges for granted sometimes, so I want to draw attention to one of the underappreciated functions of this facet of higher education.

Dichloroacetate not yet an effective treatment for aggressive brain cancer

Fri, 14 May 2010 17:02:53 -0500

Dichloroacetate or DCA is a small molecule that has been in the press over the last four years due to its potential to inhibit aerobic glycolysis in cancer cells. The cells from each of us usually produce energy in the form of ATP from a variety of nutrient sources plus oxygen using a very efficient process called oxidative phosphorylation. However, when oxygen is partly depleted, such as in skeletal muscle when exercising strenuously ("going anerobic"), energy is produced from glucose by a far less efficient process called glycolysis. Glycolysis is the most primitive form of cellular metabolism [Note added: This last sentence is not correct; see below for correction from Prof Larry Moran. - APB]

The glycolytic pathway has become of renewed interest in cancer. Why? Because some but not all cancer cells differ from normal cells by using the inefficient production of ATP by glycolysis regardless of the amount of oxygen that's around. You'll hear the term "Warburg effect" used to describe this phenomenon because biochemist Otto Warburg published a famous 1956 paper in the journal, Science, suggesting that the origin of cancer lies in the ability of cancer cells to shift metabolism to glycolysis.

In the intervening years, debate has ensued that accelerate glycolysis in cancer cells is just a by-product of the oncogenic process. But we now appreciate that in some cases, the accelerating of glycolysis encourages cancer. For example, the greater level of the enzyme lactate dehydrogenase (LDH) in some cancer cells is now known to be a direct effect of the oncogenic protein, c-Myc, which by itself can cause normal cells to become cancerous.

The unusual nature of some cancer cells to rely on glycolysis even in the presence of oxygen presents an opportunity to possibly target cancer more selectively while minimizing damage to normal cells as occurs with classical chemotherapy drugs or radiation therapy. Indeed, the promise of targeting the Warburg effect in cancer is intoxicating.

At present, there are a few chemicals known to inhibit glycolysis that resemble some of the intermediates in the process but require extremely high concentrations. One is called 3-bromopyruvate - as I wrote here in 2007, this chemical inhibits both glycolysis and oxidative phosphorylation so it would have to be injected directly into the artery that feeds the cancerous tumor. The other chemical is dichloroacetate (DCA).

DCA has been around for a long time and has been used in people with inherited diseases of mitochondrial metabolism. In 2007, a group at the University of Alberta led by cardiologist Evangelos Michelakis demonstrated that very high doses of DCA can slow the progression of human tumor cells grown in immunocompromised rats. The response to this story was unbelievable with internet marketers popping up to sell the simple chemical and conspiracy theorists saying that because DCA was cheap and not patentable, no drug company would ever develop it, it was being kept a secret, and so. In truth, the work was in very, very early stages.

This didn't stop hopeful patients from seeking out DCA sellers even though DCA can be contaminated with other related substances that are far more toxic. And in the most egregious case among these DCA purveyors, an Edmonton man who purported to sell DCA online was recently arrested in Phoenix and pleaded guilty to five cases of wire fraud - not because he was selling DCA but rather a white powder comprised of some combination of sucrose, lactose, dextran, and starch.

Yes. Not even the unproven DCA. Fake DCA.

The best coverage of the DCA story was put forth by my blogging colleague, Orac at Respectful Insolence, who wrote over 20 posts on issues associated with the previous study and the internet marketing of DCA. At the bottom of this post where we wrote about this trial beginning, there is a list of links to Orac's posts as well as eight or nine of our own.

This week, the Michelakis group has published a follow-up paper in Science Translational Research that includes laboratory experiments with cell lines isolated from cancer of 49 volunteers and a phase I trial of DCA in five patients with advanced glioblastoma who were also receiving a standard anticancer drug temozolomide (Temodar®) and radiation therapy. Keep in mind that the purpose of a phase I trial is not to determine a drug's effectiveness but rather its dosing and side effect profile. This is important because DCA has never been systematically studied in patients with cancer. I have not seen the paper because my institution does not receive the journal or have electronic access. However, press reports are noting that of the four patients surviving out of the starting five, three experienced reductions in the size of their tumors.

However, we don't know if these changes were due to DCA or the other treatments the patients were also receiving - this information is not included in most reports I have read.

In fact, I've seen some reports such as this one whose title suggests that the compound is effective against aggressive brain cancer. Others are less dramatic but still misleading, using words and phrases such as "cure," "panacea," "breakthrough," and "clinical trials successful." Words such as "preliminary," "premature," or "guarded" are in short supply.

Elsie Stolte of the Edmonton Journal has written perhaps the most widely distributed article that is reasonably measured and focuses more on the fact that half the costs of the $1.5 million study was funded by individual contributions across Canada. However, even that article fails to mention that the other drugs taken at the same time may have contributed to the effects observed and there are few other slightly misleading comments.

Since I cannot yet access the paper, I wish to direct you to a superb and approachable review of the latest findings written by Dr Kat Arney at the Cancer Research UK blog, Science Update. The four closing paragraphs of her article include modified verbiage that Cancer Research UK has been using in patient information content about DCA since 2007:

It is clear that DCA is an intriguing drug - one of many currently being investigated by scientists around the world. It will be interesting to see the results of more extensive lab-based experiments and larger clinical trials of DCA. And cancer cell metabolism is certainly a productive area of research that we're actively funding.

The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK has secured a licence for an off-patent drug called fenretinide, which could be used to treat rare childhood cancers. And there is certainly no "conspiracy" by pharmaceutical companies to prevent research into DCA - there is just not enough evidence at the moment to support its widespread use to treat patients.

While these results are intriguing, it is unlikely that this one compound represents "the cure" for cancer - and it is also unlikely that DCA is the "wonder drug" that the headlines portray. Cancer is a complex and multi-faceted disease, and it can be caused by a range of different faults within the cell. It is unlikely that any single drug could ever treat all forms of the disease.

There are many promising new treatments for cancer currently in development, funded by organisations across the globe - including Cancer Research UK. If anything, these new results show why research is so important in bringing safe and effective treatments to people with cancer - they don't provide definitive answers, but they support further investigations which may yield benefits for patients in the future.

Pharmaceutical chemist Dr Derek Lowe who blogs at In The Pipeline also has a nice post on his perspective.

I look forward to reading the complete report and following up when I have more information.

Of course, you should also expect Orac to fire off a few thousand words about the paper as well.

What's my poison? Pulitzer-prize winning journalist, author, professor Deborah Blum

Tue, 11 May 2010 00:02:49 -0500

This is going to be a quick welcome to Deborah Blum (@deborahblum) who has just moved her blog, Speakeasy Science, to ScienceBlogs.

Why quick?

Because I am only 22 pages away from finishing her latest book, The Poisoner's Handbook: Murder and the Birth of Forensic Medicine in Jazz Age New York. This engaging tale of the race of science and medicine against chemical poisonings for profit and punishment features the true story of NYC chief medical examiner Charles Norris and toxicologist Alexander Gettler. Of course, the other actors are arsenic, methanol, chloroform, thallium, and radium, among others. In the teens through the mid-1930s, long before benchtop atomic absorption spectrophotometry and LC/MS instruments, Norris and Gettler devised methods to detect poisons in human tissues with high sensitivity. These advances led to the prosecution of some, the absolution of the wrongly-accused, and revealed that our own government poisoned citizens who dared to challenge Prohibition.

Blum's colorful biography accounts somewhat for her fixation with insects, chickens, monkeys, and chemistry, a discipline she pursued at Florida State University until setting her braid on fire and switching to journalism at the University of Georgia.

Blum won the 1992 Pulitzer Prize for beat reporting in a newspaper series that led to her book, The Monkey Wars, about the ethics and polarization of primate research. A couple of books (Sex on the Brain, Love at Goon Park, and Ghost Hunters) and a plethora of writing assignments since, Blum now holds an endowed chair at the University of Wisconsin and as the Helen Firstbrook Franklin Professor of Journalism.

But before I learned of her award-winning writing, I first came upon Deborah Blum as co-editor (with Mary Knudson and Robin Marantz Henig) of A Field Guide for Science Writers, the official guide of the National Association of Science Writers (NASW). The guide was recommended to me by Tom Linden, MD, when I joined the graduate advisory board of his medical journalism program at UNC-Chapel Hill in his attempt to give a scientist some background on the profession.

Regular readers know that I am a huge fan of the history of science and medicine, so you can probably understand why I can't wait to get back to reading The Poisoner's Handbook. I was also originally trained as a toxicologist and published one of my first papers on heavy metals effects in the kidney before I moved to the discipline that chemicals are best used for therapeutic benefit. Hence, I am honored to now be writing under the ScienceBlogs masthead with a wonderful writer who has been one of my inspirations and with whom I share several passions.

But while I offer I warm welcome to Deborah Blum, a part of me also wants to warn those in her real life not to leave their beverage unattended in her presence.

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

Mon, 10 May 2010 08:02:19 -0500

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.

Another McNeil OTC drug recall: quality control issues not just for generic drugs

Thu, 06 May 2010 14:02:57 -0500

Let me just say at the outset that I generally pay extra to purchase brand name medications, prescription or over-the-counter (OTC), because of concerns I have about federal oversight of generic drug manufacturers.

However.

On April 30, McNeil Consumer Products issued a voluntary recall of a litany of children's cold products under the Tylenol, Motrin, Zyrtec and Benadryl brand names.

McNeil Consumer Healthcare, Division of McNEIL-PPC, Inc., in consultation with the U.S. Food and Drug Administration (FDA), is voluntarily recalling all lots that have not yet expired of certain over-the-counter (OTC) Children's and Infants' liquid products manufactured in the United States [in Fort Washington, PA] and distributed in the United States, Canada, Dominican Republic, Dubai (UAE), Fiji, Guam, Guatemala, Jamaica, Puerto Rico, Panama, Trinidad & Tobago, and Kuwait.

The complete product list can be found at the bottom of the press release (here) from which the above quote was derived.

McNeil noted that "some of the products included in the recall may contain a higher concentration of active ingredient than is specified; others may contain inactive ingredients that may not meet internal testing requirements; and others may contain tiny particles."

However, an ABC News story on the recall provides an FDA report (PDF) indicating that some of the remedies contained as-yet unidentified gram-negative bacteria.

Your humble blogger was contacted for this story and quoted therein but I had not known at the time of the bacterial contamination. All reports suggest that these problems are unlikely to present any risks to infants and children, pending identification of the bacteria, but this cannot be good - especially since this is the third recall by the manufacturer in the last eight months.

ABC News quoted a statement released Tuesday from Johnson & Johnson, the parent company of McNeil Consumer Healthcare:

"The quality issues that the FDA has observed, many of which we had recently identified in our own quality reviews and communicated to the FDA, are unacceptable to us, and not indicative of how McNeil Consumer Healthcare intends to operate," the Johnson and Johnson statement read.

This recall is also yet another blow to the widely-held belief in the higher-quality of a brand name drug product over generic drugs, at least in the case of over-the-counter products:
"This recall provides compelling evidence that quality assurance is an issue for all drugmakers, and is not specific to generic products, as many have implied," said Dr. Jerry Avorn, professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital.

What struck me was the report from the Associated Press and the FDA's own Q&A site that until these products are back on the market, parents use alternative products with the same ingredients on the labels - i.e., generic versions of the McNeil products - rather than trying to calculate how much of an adult-strength product to use in an infant or child.

I wonder how many parents might switch to the generics, see the incredible price savings, and switch permanently to one of these products.

Commenters at several of the news site also note that there has been much ado about quality control issues at drug plants outside the US; that excuse can't be invoked in this case.

Acknowledging chronic illness

Tue, 04 May 2010 08:02:19 -0500

Wow. I really don't deserve this but I truly appreciate your concern, advice, and best wishes sent over the last few days following my post on losing, and slowly regaining, my voice. I didn't know anyone was still reading but some of you must have seen my RSS feed pop up under the cobwebs on your reader.

What's interesting is that I generally look well in person other than getting winded when walking too fast or going up stairs (yes! I can walk up stairs now! w00t!). And to be honest, the loss of 14 lbs I didn't need has actually made me look a little more fit. I've still got a long way to go in my recovery but people think I look better than I actually am.

So among the comments I received in the last few days was an exceptionally prescient and timely one from Lisa Copen. She wrote the following in response to my February 7th post, "Meditations on those with chronic illness," a post I wrote when I was about at my worst.

Thank you for your kind simple words at the end of your post that say, "So today, my heart goes out to all of those who suffer with chronic illnesses every day. You have my admiration and respect."

As the founder of National Invisible Chronic Illness Awareness Week (and a patient of 17 years of rheumatoid arthritis) I can say that just hearing the simple validation from others is what people crave most. We did a survey a few years ago and with over 1500 respondents what they "hate" hearing the most is "but you look so good!" There is some part of our human nature, despite whatever kind of suffering we are going through, be it physical,mental, emotional, financial, whatever - that desires someone to say, "I don't know how you do it. I respect that it is hard and you inspire me."

Blessings on your continued endeavors.

Lisa didn't mention it in her comment but she is also founder of a non-profit group called Rest Ministries, "a Christian organization that serves the chronically ill through a variety of programs and resources." I also added the link to National Invisible Chronic Illness Awareness Week because Lisa didn't have it. We get a lot of self-promotional stuff here in comments and e-mail but Lisa's comment clearly came from the heart. So, I'll promote her work for her because she's doing good stuff.

While I haven't vetted all of the medical information at Rest Ministries, it seems to have a lot of useful suggestions and tools for those with chronic illness and their caregivers and loved ones. A quick glance at their section on alternative treatments wisely notes the risks of infection with acupuncture and suggests instead more useful motion exercises such as tai chi. For folks needing help around the house, they note how to go about screening cleaning services. They have what looks like a good bookstore and I may even have to buy one of their $8.50 T-shirts that have 33 ways to encourage a chronically ill friend (jpeg of shirt back).

Even if you are of another faith, atheist, or agnostic, you may find something useful there.

Thank you, Lisa, for stopping by.

My voice has been absent from the blogosphere. . .

Sat, 01 May 2010 23:02:39 -0500

. . .because my voice has also been absent from the offline world.

Yes, the final gift to me from LungMutiny2010 is a case of inhaled corticosteroid dysphonia - and another opportunity to cultivate compassion for those with chronic illnesses and permanent loss of physiological functioning.

Here's a recap: After a three month battle with pneumonia, I returned to the university as much as I could about six weeks ago. I say "as much as I could" because, once again, I was amazed by how little my body would let me do after being confined to bed for ten weeks.

Some days I'd just be doing great and, without warning, hit a wall of complete exhaustion - the kind that even a triple-venti, quadruple-espresso shot beverage couldn't remedy. Other days I'd wonder why the soles of my feet were red and burning - I had to remind myself that my walk across campus the preceding day was a little much on feet that hadn't walked, much less seen shoes, for most of the year.

But even as my stamina is on an upward trajectory, I still had laryngitis as my pulmonary symptoms resolved. I kept waiting for it to improve as I tried to talk through the hoarseness.

Then three weeks ago, I lost my voice to all but a whisper.

Fortunately, one of our local academic medical centers maintains a voice care clinic out of their Division of Otolaryngology. I was able to get in within a week to see one of the senior docs in the group and an outstanding team of nurse practitioners and speech pathologists. After lengthy questioning about my allergy/asthma history and the course of my illness to date, they anesthetized my nasal passages with tetracaine spray and viewed my vocal cords with a strobscopic laryngoscope.

The technology was awesome to watch in the recorded video but confirmed that my vocal cords were bright pinkish-red and swollen with irregular edges. "That's about as bad as we see them around here," was the quote from my doc as he pointed to the monitor. I forgot to ask if there was a way for me to download some stills to show you here.

It seems likely that the large amounts of oral corticosteroids followed by inhaled steroids did a great job helping my lungs heal but set up my vocal cords for a Candida infection (fungal), steroid myopathy, or some combination thereof.

Yes, it's a major bummer to have what would be called an iatrogenic adverse effect but without these steroids, I'd still be on my back in bed. I make this point because no drug possesses absolute safety. All drugs have a some spectrum of benefits and risks of side effects - the setting in which they are used determines whether those benefits outweigh the risks. I would take these steroids again in a heartbeat. Remember, those who have followed this saga: I was coughing so hard that I was passing out (cough syncope) and I believe I either cracked a rib or tore a tendon from the months of hacking.

I did some reading after another colleague told me of the prevalence of this inhaled steroid side effect. Inhaled corticosteroid dysphonia was first widely described in the literature in 1983 by a group from East Birmingham Hospital in England. In recent years, this adverse reaction seems to have increased in incidence with the introduction of dry power inhalers, usually in the form of the longer-lasting steroid fluticasone.

This 2004 Laryngoscope article from the University of Pennsylvania describes the problem and the pathology quite well.

So, I've been ordered to a few things that include stopping the inhaler for the time being - something I can do since my lungs have improved so much. The bigger challenge is to steer clear of any irritants or allergens - a tall task in springtime in North Carolina. I've actually been directed to stay home and work on the computer but that's impossible given the number of thesis defenses and search committee interviews currently ongoing.

I've also been directed to a strategy to lower the viscosity of nasal and pulmonary secretions by drinking about a gallon of water each day - about six, 20 oz bottles of water (I use a big cup that I refill with filtered water to save the plastic from going into the landfill). That's about 3780 mL/day for non-US readers. An additional approach to minimize secretions and purge allergens has been to use nasal irrigation daily with a warm mixture of sodium chloride and sodium bicarbonate.

But the greatest challenge has been to follow the edict to completely rest my voice for two weeks - not even whisper.

For the first few days, I walked around with a pad of paper and an introductory statement about why I couldn't talk. But when people are standing over you waiting for you to finish writing, it becomes much faster to just whisper.

Yes, I know. I'm not supposed to whisper. If I could have stayed home and done all my work from there, I would have. I even had a nice letter from my doc to give to my boss and the HR department ordering me to work from home.

What's funny is that when you start to whisper, other people whisper back to you. Even when they know you are whispering because of voice restrictions, the automatic response is to whisper in reply.

Much of my communication with others has been via writing - and I've been writing a lot. That seems to be one reason that I haven't been blogging. Writing takes longer than picking up the phone so I've seemed to have very little discretionary time lately to write for fun.

But I've wanted to write - yes, about science - but also about this additional opportunity to think about something we take so much for granted: the ability to speak. I am lucky. My voice will come back. I've though a great deal about how fortunate I am.

What also came to mind was the now-famous Esquire article I read about movie critic Roger Ebert during the worst of my pneumonia in mid-February.

Ebert lost his voice permanently about four years ago following surgeries for thyroid cancer that had metastasized to his now-removed lower jaw, plus radiation treatments that caused a near-fatal breach of his carotid artery. The Esquire article by Chris Jones is brilliant in how it captures the man and his wife Chaz as their life has transitioned. While it is clear that Ebert misses the ability to speak, he deflects any pity noting how happy he is and how his writing has exploded in the past few years, not just in number of words but in the magnitude of attention to his work.

His online journal - a blog at the Chicago Sun-Times - counted 93 million hits last year and his individual posts can garner hundreds of comments.

Many folks who've lost their voices don't have the options Ebert has, such as working with companies on voice synthesis, particularly in mining his years of television and DVD shows to give his computer the ability to make him sound like Ebert again.

Most folks who lost their voices due to cancer or other diseases don't have the option I have - to whisper - or to hope that their voice will come back in a few weeks or months.

This short time without a voice has taught me just how valuable it is, just as months with pneumonia have taught me how important good health is. I never understood when my elders would say, "Well, at least you have your health." This year has helped me understand that much better.

I get scoped again next Friday to see how things are doing. Hopefully I'll be able to get back to some more blogging in the meantime.

I've missed y'all, so I hope that each of you are well in your parts of the world.

Attention Evil Geniuses and Kids: MakerFaireNC today!

Sun, 25 Apr 2010 10:02:09 -0500

So you ran any number of 5K charity races yesterday or went on the Piedmont Farm Tour. But it's a rainy Sunday in the Southeast and you're wondering what to do with a house full of cooped-up kids, especially if it's too soggy to do day two of the farm tour.

Let me suggest that you get to Durham, NC, to MakerFaire:NC.

Maker Faire is an annual event organized by the people who bring us MAKE Magazine. Maker Faire:NC is a fully sanctioned event but is being planned and coordinated by Raleigh/Durham locals. Our goal is to bring together Makers, Crafters, Inventors, Evil Geniuses, Scientists, Artists, and anyone else interested in learning from NC, SC, VA, DC, and beyond.

Maker Faire:NC is FREE to attend thanks to our generous sponsors and commercial exhibitors.

Just like the bigger Left-Coast version, Maker Faire:NC celebrates things people create themselves -- from James Bond-worthy electronic gizmos to Martha Stewart-quality "slow made" foods and homemade clothes. Inspiration is ubiquitous at the festival and there are surprises around every corner for people of all ages.

Regular readers who follow the creative activities of Toaster Sunshine at Mad Scientist, Jr. will know a little more about what these life and tech hackers do.

Here's the Quick FAQ but the details are:

Where: Indoors at Loehmann's Plaza, 1821 Hillandale Rd, Durham, NC 27705

When: Today, Sunday, April 25 - 9 am to 9 pm

Cost: $0.00

There will be wi-fi available for two bucks if you need it.

Here's a list of the exhibitors to get a flavor of the stuff that will be there.

MakerFaireNC is run by a professional events company under the local guidance of Jonathan Danforth, an audio/video/artist/multi-tech guy I first learned of from his expertise in daguerreotypes.

The PharmKid and I will be rummaging about. Follow us on Twitter @AbelPharmboy.

Overheard from a breast oncologist...

Fri, 23 Apr 2010 07:26:27 -0500

KFC and Komen?

BucketsfortheCure.com?

Why don't they just put a pink ribbon on a pack of cigarettes?

Cytogeneticist Dr. Janet Rowley receives AACR Lifetime Achievement Award

Mon, 19 Apr 2010 10:19:00 -0500

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.

Writing to publish vs. writing to be read

Sat, 17 Apr 2010 11:02:15 -0500

I've often remarked that the beauty of this blog is that more people read here every day than I would reach in even the largest class I teach. Moreover, far more people read this blog than will ever read my peer-reviewed scientific publications. And that's even considering that we have very modest traffic numbers here for ScienceBlogs.com. Of course, Terra Sig readers are very discriminating - and good-looking, erudite, and probably even smell good, too.

This morning, my Twitter feed brought me a post from the blog, University of Venus, as referred to me by HASTAC Director of New Media Strategy, Ruby Sinreich. (Local readers will recognize Ruby as the far-better half of Carrboro Creative Coworking founder and new media god, Brian Russell, and mother of Izzy.)

Mary Churchill wrote a post there entitled, "Why Do Academics Write?," a common theme that has emerged in her recent off-blog conversations. Therein, she muses about writing narrow academic books for promotion and tenure that appeal to the select elite in your field versus writing for a broader audience, in her case, on the University of Venus, "a collaborative blog venture bringing together the voices of GenX women in higher education across the globe."

For those of us in the sciences whose productivity is measured in peer-reviewed research manuscripts, one can ask why we write blogs. Personally, I enjoy the conversation with all of you, fellow scientists as well as folks far afield who happen to be interested in science and drugs. The blog also allows me to explore outside of my field - cancer research - and learn more about such areas as neuroscience and geology and even further to music, history, and, yes, writing. Through this community I've also been able to continue my education by learning about issues of gender and racial and ethnic diversity in both the sciences and society. I definitely feel more well-rounded as both an academic and a human being by writing here and engaging with this community. And I am still learning.

As for the argument that blogging is a waste of time and a distraction - well, I may spend about an hour a day writing and give up watching one episode of NCIS. Maybe an additional sporadic half hour doing literature searching, scanning news articles, and reading the writing of others I enjoy and respect or those they recommend.

I've also found the blog to be valuable academically, especially in teaching, as a place I can go back to for lecture topics complete with images and links and notes about papers I have read. Comments and related links offered by readers allow me to learn even more because these suggestions come from people who are expert in those fields. Plus, I can also find information on my blog much easier than I can in my file cabinet.

But I'm more interested in why those out there who must write professionally also write for fun, because you want to, not because you have to. I'm not looking only for comments from bloggers but also from those of you who might write poetry, curate a discussion group.

So, why do you write when you don't have to?

Indiana University student's suicide due to hydrogen sulfide (H2S)

Wed, 14 Apr 2010 22:02:50 -0500

Down on the left sidebar you'll see a little gizmo for SiteMeter, a service that measures one's blog traffic and gives all sorts of tidbits about how readers got to the blog and a very general idea of where they are coming from. Most bloggers pay attention to the numbers of visitors but I have always been more interested in how readers get here and what posts they are reading.

One value of SiteMeter is to keep tabs on search terms that bring people here to learn of breaking stories. So, when I saw a bunch of hits starting yesterday with search terms like "hydrogen sulfide," I feared the worst: that another young person had committed suicide by mixing household chemicals to release the toxic and potentially fatal gas and search engines were driving traffic to one of my earlier hydrogen sulfide posts.

Indeed, this story is more heartbreaking than usual (not that any suicide isn't) because it was a highly-promising young man who was an academic standout in the sciences and a musician:

Gregory Willoughby was an academic standout at Warren Central before he began his study at IU. This community as well as the Bloomington campus is shocked to hear of his death as police continue to search for answers.

A junior at Indiana University, Gregory Willoughby was an accomplished academic and musician. A biochemistry major with minors in mathematics and psychology, Willoughby was a chemistry tutor who played the cello. [According to the IU student newspaper, Willoughby was co-principal chair in the All-Campus Orchestra in spring 2008.]

In 2007 he was named a Wells Scholar, one of the most competitive and prestigious awards offered at an American university.

The young man was found in his closet with a bucket of liquid, a sign on the door reading, "Warning H2S," a common feature of recent cases of suicide by this method. As in this other case we wrote about, the victims seem to care more about the safety and welfare of others than that of themselves.

The account from the Indiana Daily Student leads me to believe that Mr. Willoughby lacked a support network. The medical examiner estimates that young man was dead for seven to ten days. Caitlin Johnston writes that few people in the Willkie dormitory actually know one another and it is described as "a closed off community for independent people." So even if Willoughby had been experiencing suicidal thoughts that might have been evident in his behavior or language, it doesn't seem that anyone would have known.

However, he is reported to have been a research assistant in the Cognitive Neuroimaging Laboratory in the Department of Psychological and Brain Sciences. Beyond no one there recognizing any warning signs, I'm surprised that his absence was not noted by anyone in the laboratory. Or by any of his professors in class.

But then again, suicidal signs are not always evident. Early in my career, a top student in my pharmacology class committed suicide with sedatives over a weekend. She had sat in the front row, right in front of the lectern, and her best friend said she had been to the opera with her the very night she overdosed without any indication that she was distraught.

I have yet to find any comments in any news stories to date that come from any friends or family. [Since writing this, a great many friends, family, lab co-workers, and fellow students have come forward to comment below and in subsequent coverage by the Indiana Daily Student. According to commenters below, reporters (with the exception of Caitlin Johnston at the student paper) were less than sensitive in seeking background information.]

This case makes me very, very sad.

Addendum April 15th: You will see in the comments below the outpouring of love for Gregory from people who knew him. One noted specifically that they chose not to respond to interview requests. I am grateful to those of you who have taken the time to express your sentiments and share your stories. You have my personal condolences on the tragic loss of this fine young man who you know and love.