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History, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Did microbes mess with Typhoid Mary’s macrophages?

Did microbes mess with Typhoid Mary's macrophages?

macrophage with salmonella insideMary Mallon (a.k.a. “Typhoid Mary“) didn’t mean any harm to anybody. An Irish immigrant, she made her living for several years about a century ago by cooking for better-off families in the New York City area. Strangely, the people she cooked for kept on coming down with typhoid fever – but not Mary.

Mallon, alas, turned out to be a chronic asymptomatic carrier of Salmonella typhi, the bacterial strain that causes typhoid fever. Typhoid is a deadly disease that, while no longer a huge problem in the United States, infects tens of millions – and kills hundreds of thousands – of people around the world every year.

“She didn’t know she had it,” says Stanford microbiologist Denise Monack, PhD. “To all outward appearances, she was perfectly healthy.”

Salmonella strains, including one called S. typhimurium, also cause food poisoning in people and pets, taking an annual human toll of 150,000 globally. While S. typhi infects only humans, closely related S. typhimurium can infect lots of mammals.

Between 1 and 6 percent of people infected with S. typhi become chronic, asymptomatic typhoid fever carriers. Nobody has known why this happens, but it’s a serious public-health issue. To address this, Monack has developed an experimental mouse model that mimicks asymptomatic typhoid carriers. In a new study published in Cell Host & Microbe, she and her colleagues put that model to good effect, showing that Salmonella has a sophisticated way of messing with our immune systems. The bacteria set up house inside voracious attack cells called macrophages (from the Greek words for “big eater”). Macrophages, are known for their ability to engulf and digest pathogens and are called to the front lines of an immune assault against invading microbes. Ornery critters that they are, macrophages would seem like the last thing bacteria bent on long-term survival would want to meet.

But, as I wrote in my release about this study, a macrophage has two faces, depending on its biochemical environment:

“Early in the course of an infection,” [Monack] said, “inflammatory substances secreted by other immune cells stir macrophages into an antimicrobial frenzy. If you’re not a good pathogen, you’ll be wiped out after several days of causing symptoms.” But salmonella is one tough bug. And our bodies can’t tolerate lots of inflammation. So, after several days of inflammatory overdrive, the immune system starts switching to the secretion of anti-inflammatory factors. This shifts macrophages into a kinder, gentler mode. Thus defanged, anti-inflammatory macrophages are more suited to peaceful activities, such as wound healing, than to devouring microbes.

And, sure enough, Monack and her colleagues showed that salmonella germs have a way (still mysterious, but stay tuned) of taming macrophages, flipping an intercellular switch inside of these thug-like cells that not only expedites their champ-to-chump shift but induces them to pump out tons of glucose, the bug’s favorite food. What better place to hide than in the belly of the beast?
Previously: TB organism’s secret life revealed in a hail of systems-biology measurements
Photo by AJC1

Cancer, History, In the News, Science

Some resolution for the immortal cells of Henrietta Lacks

Some resolution for the immortal cells of Henrietta Lacks

We’ve written quite a bit here about Henrietta Lacks, the poor black woman who died in 1951 of cervical cancer, and whose cancer cells – taken without her knowledge – led to great advances in biomedical research. (Lacks’ story was told in the award-winning The Immortal Life of Henrietta Lacks.) Lacks’ family, in the words of Smithsonian blogger Rachel Nuwer, have “harbored a deep discontent about their relative’s stolen cells;” “they were never informed that Lacks’ cells were taken; they never received any royalties from the HeLa line; and researchers often ignored Lacks’ great personal legacy.”

Today, there’s big news about Lacks, with Nature reporting that the family reached a deal with the National Institutes of Health regarding access to the so-called HeLa cells. Ewen Callaway explains how the agreement came to be and also addresses the issue of financial compensation:

Some Lacks family members raised the possibility of [it],[NIH director Francis] Collins says. Directly paying the family was not on the table, but he and his advisers tried to think of other ways the family could benefit, such as patenting a genetic test for cancer based on HeLa-cell mutations. They could not think of any. But they could at least reassure the family that others would not make a quick buck from their grandmother’s genome, because the US Supreme Court had this year ruled that unmodified genes could not be patented. [Henrietta’s granddaughter Jeri] Lacks-Whye says that the family does not want to dwell on money — and that her father has often said he “feels compensated by knowing what his mother has been doing for the world.”

Previously: Do you have a ‘HeLa’ story? Share it with Rebecca Skloot, Will Henrietta Lacks now get her due?, Image of the Week: HeLa cells and Immortal cells: Henrietta Lacks lives on and on

Health Costs, Health Policy, History, Stanford News

The history of U.S. health care in about 1,000 words

The history of U.S. health care in about 1,000 words

“All men are created equal” may be the guiding legal principle for citizens of the United States, but not when it comes to health care coverage and outcomes, says Victor Fuchs, PhD, one of the nation’s foremost health economists and the Henry J. Kaiser Jr. Professor, Emeritus, at Stanford.

In a Viewpoint published today in the Journal of the American Medical Association, Fuchs provides a history lesson on how and why the U.S. health care system spends more than double on per-person health expenditures than other advanced nations, and he offers some strategies for controlling future costs.

“This is the best short piece on U.S. health care that I’ve ever seen,” Howard Bauchner, MD, editor-in-chief of JAMA, told me.

Beginning today, the Affordable Care Act expands the number of Americans receiving preventive care, providing new federal funding to state Medicaid programs that choose to cover preventive services. It also requires that states pay primary care physicians no less than 100 percent of Medicare payment rates for primary care services.

While the health-care reforms mandated in the act include some provisions to motivate health-care providers to become more efficient, less fragmented and more accountable, it doesn’t include revenue sources for all its new services. Fuchs says, “More comprehensive reforms are necessary to avoid financial disaster.”

According to Fuchs, there are three fundamental differences in the U.S. system — driven by its history — that make it difficult for the U.S. to adopt a less costly government-financed health care system. There is a distrust of large government that began when America broke away from the strong-armed British Empire. There is a reluctance to redistribute wealth across all citizens, in part because of the country’s cultural diversity. And there are “choke points” in the U.S. political system — such as the cost of election campaigns and the Senate filibuster — that give deep-pocketed special interest groups the upper hand in preventing sweeping reforms.

As a new Congress returns to work with health care reform high on its new year’s resolutions, Fuchs’ editorial provides a starting point, grounded in history, for a new round of negotiations.

Previously: Study: If Americans better understood the Affordable Care Act, they would like it more, Does the Affordable Care Act address our health-cost problem?, Stanford economist Victor Fuchs: Affordable Care Act “just a start” and An expert’s historical view of health care costs

From Dec. 24 to Jan. 7, Scope will be on a limited holiday publishing schedule. During that time, it may also take longer than usual for comments to be approved.

History, Medicine and Literature

Top medical reads of 2012 from Stanford Medicine’s editor

As the editor of Stanford Medicine, I think a lot about new research, new discoveries, new treatments. So it’s no wonder I find stories of long ago a refreshing change when I’m reading for pleasure. A look at my 10 favorites this year shows my predilection, though there’s lots of new here too. History fan or not, if you read just one, read about the immortal jellyfish! I can’t stop thinking about them.

Undead: The rabies virus remains a medical mystery, by Monica Murphy and Bill Wasik, Wired
An account of a modern attempt to cure rabies, with lots of history woven in.

Can a jellyfish unlock the secret of immortality? by Nathaniel Rich, New York Times Magazine
Including wondrous jellyfish that grow younger and a researcher who breaks the mold, and it’s told with humor and lyricism.

Two hundred years of surgery, by Atul Gawande, New England Journal of Medicine
For gems like this: “Liston operated so fast that he once accidentally amputated an assistant’s fingers along with a patient’s leg, according to Hollingham. The patient and the assistant both died of sepsis, and a spectator reportedly died of shock, resulting in the only known procedure with a 300% mortality.”

Post-Prozac nation: The science and history of treating depression, by Siddhartha Mukherjee, New York Times
Everything we knew about antidepressants like Prozac was wrong. But that’s OK.

The nature of the Knight Bus, by Chris Gunter, Story Collider
A look behind the scenes at top science journal Nature from one of the journal’s editors.

The island where people forget to die, by Dan Buettner, New York Times Magazine
On mellowing out on a Greek island to live to 100. It got me thinking about how to bring more mellowness into my life.

Fear fans flames for chemical makers, by Patricia Callahan and Sam Roe, Chicago Tribune
A great investigation into a chemical industry-funded front group’s deceptive campaign that fueled demand for flame retardants in furniture, electronics and baby products among many other items. The whole four-part series is worth reading. It also explains that the chemicals have been linked to cancer, neurological deficits, developmental problems and impaired fertility — and not only that, but they don’t work.

The measured man, by Mark Bowden, The Atlantic
On one man’s effort to use big data as a tool to guide him to better health. This is either insane, the future, or both.

A family learns the true meaning of the vow ‘in sickness and in health’, Washington Post Magazine
A heartrending, inspiring read for me, though not for all – as evident by the comments.

Previously: My top medical reads of 2011 (aside from those I edited)

From Dec. 24 to Jan. 7, Scope will be on a limited holiday publishing schedule. During that time, it may also take longer than usual for comments to be approved.

History, Medical Education, Medicine and Literature, Medicine and Society, Technology

From the archives: A 1949 satirical prediction of medical education and life in 2000

From the archives: A 1949 satirical prediction of medical education and life in 2000

Throughout history, mankind has been making predictions about what the future will hold. While many of us only think a few years ahead, two enterprising interns working in 1949 at STAT, a publication from the Stanford School of Nursing (which no longer exists), daydreamed what life would be like at the start of the new millennium.

A colleague of mine stumbled upon the authors’ fun and satiric article (.pdf) not long ago, and I decided to take a moment to compare their predictions with reality. The story is set in the year 2000, where everything is done on screens and the world runs on the latest technologies of a fictitious technology conglomerate named Tele-Tele Inc.

While the story presents a lot of far-fetched and comical ideas of life in 2000, the imagined world of Tele-Tele Inc. actually has a few similarities to modern-day life. In one part of the story, the narrator explores how the School of Medicine has changed:

…I decided to take a look at the old Med School. Surely, this would not be changed by Tele-Med. But to my utter amazement, I found only a large Tele-Transmitter, which I was to learn later, would be used to send Tele-Lectures to the New Tele-Med Students. I was also to learn that these Tele-Lectures could only be received on specially built ceiling screens, designed to put the students in an obviously comfortable position.

Could this have been an early prediction of YouTube and Skype as a way for students to follow lectures?

The article also foretells the impact that advancements in technology would have on patient health care. I spoke about this with article co-author Eldon Ellis, a 90-year-old retired surgeon, who told me:

It’s really important to not let the relationship between doctor and patient get lost in all the technology. Unfortunately, the good features of technical changes sometimes get overwhelmed, and the first thing someone gets is a batch of X-rays and lab studies. What we really need to do is look at the patient and talk to the patient.

The full article is worth a read.

Cancer, History, Public Health

Cigarettes and chronographs: How tobacco industry marketing targeted racing enthusiasts

Hot on the heels of reading about the tobacco industry’s connection to the Olympics, I’ve just come across a post on Hodinkee (a great watch blog) detailing a surprising relationship between Swiss watch manufacturer Uhrenmanufaktur Heuer AG (now TAG Heuer) and Brown & Williamson. According to Jeff Stein, the relationship arose out of a need to better position Viceroy cigarettes:

For years, Viceroy’s advertising theme had been balance–”not too strong, not too light, Viceroy’s got the taste that’s right.” A normal ad might depict a woman offering her companion one of her cigarettes, and he, surprisingly, enjoys the taste. The Viceroy was “less masculine than its key competition,” and the brand had a “feminine orientation,” according to internal documents. While the Viceroy couple shopped for flowers, the Marlboro man rode his horse straight into more market share.

The solution, Stein writes, was to make Viceroy the brand of the “auto racer.” To help shape that perception, Brown & Williamson partnered with Heuer to offer a discounted chronograph wristwatch ($88!) with the purchase of a carton of Viceroy cigarettes:

Brown & Williamson contacted Heuer in late 1971 with the idea of offering the Heuer Autavia in a Viceroy promotion. Throughout the 1960s, Heuer was a dominant presence at the racetrack. Its stopwatches, handheld chronographs, dashboard timers, and timing systems were the gold standards in their respective categories.

I don’t want to spoil the rest of the entry, so head over to Hodinkee if you’d like to see another example of how the tobacco industry has, in Jackler’s words, “affiliated its products with cherished and admired cultural icons.”

Previously: A discussion of the tobacco industry’s exploitation of “smoke-free” Olympic Games

History, In the News, Surgery

Release of WWI medical records may help reconstruct historical developments in plastic surgery

Release of WWI medical records may help reconstruct historical developments in plastic surgery

An article that appeared in The Telegraph today announced the release of medical records documenting World War I plastic surgery operations on wounded British soldiers.

Although many of the records are only available to descendants of the veterans, the article features an amazing set of before and after photos for one particular soldier. The images may be hard to look at for some, but they also illustrate the breakthrough work of plastic surgery pioneer Harold Gillies, MD, and his brilliant contributions to the field of reconstructive face surgery.

Family historian Debra Chatfield explains in the article:

The medical world owes a great deal to Dr Gillies, as do those who were treated by him in the early twentieth century and anyone who has ever received plastic surgery treatment since then. Without his pioneering developments in this field, plastic surgery might not be as advanced as it is today.

These records are an important source of information for historians, the medical world and those interested in learning about the reality and aftermath of World War I.

Previously: In scar wars, a new hope

History, Medicine and Literature

Slideshow of beautiful and important scientific texts

Wired Science has a nice, succinct slideshow highlighting a selection of important scientific texts. Among them, of course, is Gray’s Anatomy. Tanya Lewis writes:

Without the work of intellectual giants like Einstein, Newton and Darwin, we might still be in the dark ages. But how many scientists still read the dust-ridden texts where these luminaries first expounded their theories? Thanks to the internet, you no longer have to hunt down these yellowing tomes in a moldy library vault. Here’s the story of 9 famous publications that spun the scientific world off its orbit.

If you have a few minutes, it’s worth looking through.

Photo from Gray’s Anatomy from Wikimedia Commons

History, In the News

Rediscovered report details Lincoln’s final hours

As has been covered widely in the news, a researcher hunting through the National Archives for letters by Abraham Lincoln recently uncovered a doctor’s report of the 16th president’s assassination.

Army surgeon Charles Leale, MD, attended the theater the night the President was killed and was the first doctor on the scene. The report reads:

“Having been the first of our profession who arrived to the assistance of our late President, and having been requested by Mrs. Lincoln to do what I could for him I assumed the charge until the Surgeon General and Dr Stone his family physician arrived, which was about 20 minutes after we had placed him in bed in the house of Mr. Peterson opposite the theatre, and as I remained with him until his death, I humbly submit the following brief account.”

A news article from CNN captures the reaction of the researcher, Helena Iles Papaioannou, who works for Papers of Abraham Lincoln:

“You get a sense of helplessness,” said Papaioannou. “I think it was fairly immediate that he realized that the president wasn’t going to recover.” Papaioannou said that, to her, the most moving part of Leale’s report is his account of covering Lincoln shortly after the president was carried to a back bedroom of the Peterson House.

“He talks about how the president’s legs — his lower extremities, from the knees down — were cold, and they brought him hot water bottles and hot blankets. I find that a very touching part of the report.”

The report largely confirms other accounts of the assassination, but adds a few details about times and pulse rate during the night.

via 80beats
Image by the Papers of Abraham Lincoln

History, Videos

TEDMED talk highlights the medical facets of the first manned mission to the moon

TEDMED talk highlights the medical facets of the first manned mission to the moon

TEDMED curator Jay Walker took the stage at last month’s conference to share a medical artifact from the historic Apollo 11 mission. In the brief talk above, Walker recounts the heartstopping tale of the first manned mission to the moon and displays Buzz Aldrin’s electrocardiogram readout in the final moments before Neil Armstrong uttered the iconic phrase “the Eagle has landed.”

Via Medgadget

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