Sir James Black (1924-2010) – Physician, Pharmacologist, Gentleman

Have you ever taken one of the now-over-the-counter heartburn relief remedies like Tagamet, Zantac, or Pepcid?
How about the beta-blocker atenolol (Tenormin) or metoprolol (Lopressor) for antihypertensive therapy, or the original less-selective beta-blocker propranolol (Inderal) for migraines, presentation anxiety or stage fright?
If you answered yes to either question, you owe a debt of gratitude to Sir James Black, the Scottish physician who left us earlier this week at age 85. The best obituary I have seen memorializing Sir James comes from the UK Telegraph.

Black was called the father of analytical pharmacology and was said to have relieved more human suffering than thousands of doctors could have done in careers spent at the bedside. Certainly, no man on earth earned more for the international pharmaceutical industry.
Yet though he became joint winner of the Nobel Prize for Medicine in 1988, Black derived little personal financial benefit from his discoveries. Among businessmen he had a reputation as an irascible maverick and this prickly independence, combined with an antipathy to big institutions, led him to flounce out of jobs whenever he felt corporate short-sightedness was getting in the way of research.

Others can be read at The Independent, The Times, The Guardian, The Scotsman, and BBC News.
It is rare for a scientist to discover one drug that makes it to market. Sir James not only led the discovery of two major drugs, propranolol and cimetidine. As if that were not enough, each drug was a “first-in-class” agent, the first approved drug that acts via a novel mechanism of action.

Correction to James Ray Sedona sweat lodge post

Our post on drugs and documents found in the Sedona resort room occupied by self-help guru James Ray requires a correction and a clarification related to the Michigan doctor of osteopathy who, according to publicly-available records, prescribed some of the drugs as detailed in these publicly-available documents.
1. Correction: Dr. John Crisler was referred to as an “Internet physician from Michigan.” To be clear, he is a physician with an office in Lansing, Michigan, with an internet presence at allthingsmale.com. On his website, he lists an “Office Visit Fee – Office or Virtual” for $60.00 and “Anti-Aging Consultation” for $495.00. The patient information link on this page leads to a “Coming Soon” placeholder.
2. Clarification: According to his website, Dr. Crisler’s medical practice specializes in “testosterone replacement therapy,” or TRT, to treat hypogonadism. His frontpage prominently displays his talks and memberships in the “anti-aging” community. Some of the drugs employed in TRT are also used by bodybuilders but the apparent intention of TRT is to restore normal testosterone levels. In the case of Mr. Ray, the publicly-available document from the search warrant affidavit simply refers to the drugs as “treatment therapy.”
For reference, this was the paragraph from the original post:

Dr. Crisler operates the website, allthingsmale.com, and offers in-clinic and online consultations. The frontpage of his site argues strongly that he is in the business of anti-aging therapies as shown lecturing to the American Academy of Anti-Aging Medicine and offering subscriptions to Life Extension Magazine. Further exploration of his website reveals that he specializes further in assessment of low testosterone levels, or hypogonadism.

I welcome any and all feedback to clarify this post. I would, however, encourage first that one read the original post in its entirety.
Questions came to light after two posts went up on discussion forums at the All Things Male MuscleChatRoom.com and the anabolic steroids section of Meso-Rx Men’s Health Chat at mesomorphosis.com. We received 98 and 90 hits, respectively, from each of those sites (barely 5% of our last 4000 visits) and several commenters protested that TRT was being unfairly conflated with bodybuilding anabolic steroids.

It really pisses me off the way that he keeps referring to it as anti aging/bodybuilding, as thou it were some undercover way of getting steroids for bodybuilding enhancement.

d00d, do you not see the irony that you wrote this on a forum called “MuscleChatRoom?”
But I do stand corrected and will refer to this drug combination as testosterone replacement therapy. I suspect that as I age and face the inevitable decline of testosterone levels, I may become a candidate for such therapy.
My original post did make a lengthy point that, in medical terminology, testosterone is a steroid with anabolic activity but that the general public thinks of anabolic steroids as the semi-synthetic compounds sold on the black market. Testosterone, instead, is a naturally-occurring anabolic steroid that is available by prescription as a transdermal patch, gel, or injection.
The primary purpose of the post was to document the backstory on my ABC World News Sunday appearance last week where I was asked to comment on whether these agents had the potential for inducing in Mr. Ray behaviors that could have contributed to his actions observed at the sweat lodge tragedy in October. Last Sunday’s article celebrating the life of Kirby Brown, a victim from Los Cabos, describes these events. I noted that I am not a board-certified endocrinologist, or a physician for that matter, and that I could only comment on the effects that the drugs could have in a hypothetical person. Moreover, I was not privy to Mr. Ray’s behavior prior to being prescribed these drugs.
However, I’ll leave it to the reader to peruse the forum threads at MuscleChatRoom and Mesomorphosis to observe the personalities of other TRT users. Props to anyman for rising above the fray.

Another addition to the tribe and honor for physician and humanitarian, Dr. Robert A. Hingson

In discussing the Christmas birth of a son to ScienceBlogs launcher and science journalist Christopher Mims and his wife, I neglected to note another addition to our tribe of science, from a science blogger specifically.
ChemicalBiLOLogy blogger, Arlenna, gave birth on Christmas Eve to a beautiful girl, pictured here with Mr. Arlenna. In her brief post, “I had a baby!,” Arlenna posited:

. . .whoever invented epidurals and started using them in childbirth should win the Nobel Prize.

Despite my lack of training in anesthesiology or obstetrics, I thought I might look into this a bit. I had pondered this question before on behalf of PharmGirl, for whom epidural anesthesia played a prominent role in the Caesarian delivery of the PharmKid.

Clifton Leaf: “a legal frenzy that’s diverting scientists from doing science”

It’s Sunday morning on the US East Coast and I really need to put the computer down to get out for a hike in the crisp, autumn air. Sunday morning is a great time to catch up on long-form writing but I won’t be the one providing it for you.
Instead, I encourage you to take 15 minutes this morning to read an “old” (2005) article in Fortune magazine entitled, The Law of Unintended Consequences, by Clifton Leaf in Fortune magazine.
This article details the impact of a 1980 amendment to US patent and trademark law put forth by Senator Bob Dole and the senior Senator Bayh, Birch. The Bayh-Dole Act transferred the inventorship of discoveries from federally-funded research to the universities, institutes, or small businesses where the work was done (good overview here). Prior to 1980, the US government held the title to any discoveries made, say, with NIH funding and the vast majority of that technology languished unlicensed.
This is the reason, for example, why the co-discoverers of the anticancer drug, Taxol, never benefited financially from the work: because the discovery was made around 1970 and its mechanism of action was identified in 1977.

Sir John Crofton, TB combination therapy pioneer – a long and admirable life

Denise Gellene in the New York Times is reporting this morning that Scottish physician, Sir John Crofton, passed away on 3 November at age 97.
Crofton is best known for implementing a combination drug regimen to treat tuberculosis, the insidious lung infection with Mycobacterium tuberculosis which decimated the US early last century and still kills 2 million a year worldwide. The concept of using drug combinations to increase individual drug potency and slow the emergence of resistance is now a mainstay of therapeutic approaches for cancer, HIV, and other infectious diseases.
Gellene reports that Crofton first investigated streptomycin for TB shortly after the drug’s discovery and isolation at Rutgers by Selman Waksman and his then-graduate student, Albert Schatz. Waksman was sole winner of the 1952 Nobel Prize in Physiology or Medicine, with the oversight of Schatz ranked by Scientific American among the top 10 Nobel snubs.
Crofton’s original 1950 letter to the British Medical Journal on use of intermittent doses of streptomycin can be seen in this PDF.
Incidentally, the revered German physician, Robert Koch, was awarded the 1905 Nobel Prize in Physiology or Medicine for the discovery of M. tuberculosis. His medical microbiology criteria, known as Koch’s Postulates, became the rubric for establishing causation of an infectious agent.

“We figured out during the case that it was saying hamburger”

From today’s article by the always-interesting Sarah Avery at the News & Observer:

After several failed attempts to extract the item, Manley was referred to another doctor, who suggested removing the entire left lung. “I said, no, I wouldn’t be doing that,” Manley says.
That’s when he decided to seek a second opinion at Duke University Medical Center.

We’ve heard of “hot tub lung” and “popcorn lung” but my chest hurts just thinking about “jagged, fast-food implement lung.”
If this case does not make it into the New England Journal of Medicine, I will be disappointed.
Photo credit: Duke Hospitals via the News & Observer
Title quote: courtesy of Dr Momen Wahidi, director of interventional pulmonology at Duke

Watching Whooping Cough Way Out West

The other day Orac at Respectful Insolence wrote about yet another case where failure to vaccinate has caused a resurgence, in this case of measles in New Zealand.
Otherwise preventable and potentially fatal diseases are popping up in communities around the world as the importance of immunization is ignored by a generation of parents who never knew these diseases.
Well, looks as though they’re beginning to find out.
I’m keeping my eye on a similar case brought to my attention by my Twitter feeds from Colorado (if I can’t be there, I’ll at least read about it). This report from the Colorado Springs Gazette tells us that the US Centers for Disease Control and Prevention are currently investigating a burst of 101 confirmed cases of pertussis (whooping cough) in Durango, CO, and surrounding areas in La Plata country and the greater Four Corners region.
(Please note that while the colloquial abbreviation for the organization is CDC, prevention (by vaccination in this case) is a key component of disease control. However, CDCP doesn’t quite roll off the tongue the same way.)
Back in January the Durango Herald News ran a story about a pertussis vaccination program in the area; I love the logical invocation of the unwritten Code of the West:

Getting vaccinated is not only sensible in terms of personal health, it is the socially responsible thing to do. It is essentially a civic duty, not unlike how trimming flammable brush protects the neighbors’ homes from fire as well.
Parents who are unsure should check their children’s immunization status. Adults, too, can check with their doctors to ensure that they have had a pertussis shot.
For anyone who needs one, San Juan Basin Health Department will hold a pertussis vaccination clinic from 5 to 7 p.m. Thursday at its office at 281 Sawyer Drive in Bodo Park. A donation of $14.70 is requested, but no one will be turned away for lack of money.

The latter point I have put in boldface is key: while we at ScienceBlogs often criticize parents, largely of comfortable means, for their anti-vaccination stances, a large swath of vaccination failures in the US is a result of an inability to pay for or access to vaccines.
Time will tell whether the latest outbreak of pertussis in the Four Corners is associated with vaccination failures.

Dr Charles is back in The Examining Room

Great news hit my e-mail box overnight: one of the premier literary physician-bloggers of my childhood days in the blogosphere has returned.

Hi all, I missed you. I missed blogging.
Just wanted to let you know that I’m returning to writing at http://theexaminingroom.com
I hope you’ll stop by, and I look forward to catching up with you all!
Dr. Charles
back from 2007 retirement

This is VERY good news for all of us, especially if you never had the pleasure of reading The Good Doctor before.
I cannot write with his clarity, of course. But I can say that Dr. Charles has a tremendous gift for communicating the depth of the emotional experience of the physician in a way that 1) restores/enhances one’s faith in the idealism of medicine, 2) makes you wish Dr. Charles was your personal physician, and 3) gives voice to the suffering and triumphs of the human condition.
From his “Opening Shop” post:

I found that in writing about medicine, I was a better doctor for it. The poetry of people’s lives, their loves, ills, and struggles was more easily perceived and appreciated. In writing about the ever-improving body of medical knowledge, I stayed better informed. In writing about my life in medicine, I sustained my energies in a healing art that has existed for as long as people have felt pain and tried to help one another with it. The reflective moment, embodied in the art, analysis, and literature we create, brings light to our present endeavors.

Several of my medblogger colleagues, many here at ScienceBlogs, do this exceedingly well when it is their focus (examples in links: (PalMD, Orac, Dr Signout). But for Dr Charles, it is a vocation.
Dr Charles actually did a short stint here at ScienceBlogs himself before closing shop. He is also the author of the 2005 book Legends of the Examining Room and was also kind enough in Fall 2006 to share with some of us trinities: writings in three, experiences of two, reflections of one.
While he is still adding to some of the back end of his pages, I certainly hope he will tell all of us where to find these books again. Dr Charles is also peppering his site with beautiful images from the NIH/National Library of Medicine online exhibition, Dream Anatomy, something I am sure will please readers and writers like Professor Tom Levenson.
Welcome back, Doctor. I’m feeling better already.
(P.S. – Doc, I am honored to be on your list of the first dozen med bloggers, especially since I am not a physician)

With love and admiration: Congratulations PharmGirl, MD!

Dear PharmGirl,
We wanted to make this note public today because a great many of our blog friends know of your dedication as a physician, wife, and a mother.
Yesterday you finished an association with an academic medical institution where you have been for half your life. From young women with breast cancer to old men in the V.A. Hospital, literally thousands have been touched by your gifts of intelligence, remarkable clinical judgment, and, perhaps most importantly, compassion. The recognition from your patients was abundant and we were privy to the personal notes of just how much you have made a difference to families faced with one of the most feared of diagnoses. Dozens of students, interns, and residents have been the beneficiaries of your tutelage and example as they pursued their own sacred paths in medicine.
But while closing this chapter for now, today you embark on a new journey and a new application of your medical training and dedication to relieving human suffering. We understand the magnitude of fortitude and soul-searching you invested to get to this day. It takes great courage to change direction in an academic medical career but we all know this is the right choice for you. In this venue, you will no doubt help thousands, if not millions, with your new knowledge and training.
You are a tremendous inspiration to your daughter of just what a woman can do with enough determination and hard work. And you are a role model for your husband to dig down deep and be the best person and soul mate that he can.
We are thrilled to be taking this exciting journey with you.
Love,
Pharmboy and PharmKid

Pediatric cancer patient checks in at age 55; beneficiary of Dr Charlotte Tan’s actinomycin D work

I love it when new readers stumble upon old posts.
Such was the case when I received the following delightful comment from Seattle-based psychologist, Dr Gary Grenell, on my April 2008 post about the passing of Dr Charlotte Tan, a pediatric cancer chemotherapy pioneer:

I was probably in one of her earliest actionmycin-D trial groups for Wilms tumor in 1957. Now at age 55, 52 years later, still going strong!

Most of you scientific youngsters today probably only know of actinomycin D as a laboratory tool for inhibiting RNA synthesis. But here in the following repost, learn about the bacteria-to-bench-to-bedside application of actinomycin D:

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This post appeared originally on 4 April 2008.
Childhood cancer chemotherapy pioneer, Dr Charlotte Tan, dies at 84
http://scienceblogs.com/terrasig/2008/04/childhood_cancer_chemotherapy.php
Actinomycin D was the first antitumor antibiotic isolated from Streptomyces parvallus cultures by the lab of 1952 Nobel laureate, Dr Selman Waksman, at Rutgers University. However, it took a young Chinese physician and the confidence in her by a future US Surgeon General for this natural product drug to positively impact the lives of children with cancer.