Published by
Stanford Medicine


Addiction, Behavioral Science, Genetics, Neuroscience, Research, Stanford News

Found: a novel assembly line in brain whose product may prevent alcoholism

Found: a novel assembly line in brain whose product may prevent alcoholism

alcohol silhouette

High-functioning binge drinkers can seem charming and stylish. The ultimate case in point: Nick and Nora of the famed Thirties/Forties “Thin Man” film series (you can skip the ad after the first few seconds).

But alcoholism’s terrific toll is better sighted on city streets than in celluloid skyscraper scenarios. At least half of all homeless people suffer from dependence on one or another addictive drug. (My Stanford Medicine article “The Neuroscience of Need” explores the physiology of addiction.) Alcohol, the most commonly abused of them all (not counting nicotine), has proved to be a particularly hard one to shake.

Alcoholism is an immense national and international health problem,” I wrote the other day in a news release explaining an exciting step toward a possible cure:

More than 200 million people globally, including 18 million Americans, suffer from it. Binge drinking [roughly four drinks in a single session for a man, five for a woman] substantially increases the likelihood of developing alcoholism. As many as one in four American adults report having engaged in binge drinking in the past month.

While there are a few approved drugs that induce great discomfort when a person uses them drinks alcohol, reduce its pleasant effects, or alleviate some of its unpleasant ones, there’s as of yet no “magic bullet” medication that eliminates the powerful cravings driving the addictive behavior to begin with.

But a study, just published in Science, by Stanford neuroscientist Jun Ding, PhD, and his associates, may be holding the ticket to such a medication. In the study, Ding’s team identified a previously unknown biochemical assembly line, in a network of nerve cells strongly tied to addiction, that produces a substance whose effect appears to prevent pleasurable activity from becoming addictive. The substance, known as GABA, acts as a brake on downstream nerve-cell transmission.

Continue Reading »

Infectious Disease, Microbiology, Research, Stanford News

Why C. difficile-defanging mouse cure may work in people, too

Why C. difficile-defanging mouse cure may work in people, too

CdiffI wrote a news release last week about a study just published in Science Translational Medicine. The study, despite it having been conducted in mice, not humans, received a fair amount of coverage – by The Washington Post, Yahoo!, Fox News, NBC, CBS and Reuters, among other places – and deserved the attention it got. It demonstrated the efficacy of a small-molecule drug that can disable the nasty intestinal pathogen C. difficile without killing it – and, importantly, without decimating the “good” bacteria that populate our gut by the trillions.

That’s a big deal. If you want to see a lot of ugly weeds pop up, there’s no better way to go about it than letting your lawn go to hell.

C. difficile – responsible for more than 250,000 hospitalizations and 15,000 deaths per year in the United States and a $4 billion annual health-care tab in the U.S. alone – is typically treated by antibiotics, which have the unfortunate side effect of wiping out much of our intestinal microbe population. That loss of carpeting, ironically, lays the groundwork for a dangerous and all-too-common comeback of C. difficile infection.

A question worth asking about this study, conducted by what-makes-pathogens-tick expert Matt Bogyo, PhD, and a team of Stanford associates: Why should we think that what works in mice is going to work in people?

The only sure answer isn’t a torrent of language but a clinical trial of the drug, ebselen, in real, live people with C. difficile infections or at risk for them. (Bogyo has already started accumulating funding to initiate a trial along those lines.)

But there’s also reassurance to be drawn from the fact that ebselen isn’t an entirely exotic newcomer to the world of medical research. As I noted in my release:

Bogyo and his associates focused on … ebselen because, in addition to having a strong inhibitory effect, ebselen also has been tested in clinical trials for chemotherapy-related hearing loss and for stroke. Preclinical testing provided evidence that ebselen is safe and tolerable, and it has shown no significant adverse effects in ensuing clinical trials.

Continue Reading »

Autoimmune Disease, Chronic Disease, FDA, Immunology, Pediatrics, Research, Stanford News

Can a safe, cheap pill prevent type 1 diabetes?

Can a safe, cheap pill prevent type 1 diabetes?

happy pillType 1 diabetes, an autoimmune disorder once known as juvenile diabetes because it tends to strike during adolescence or earlier, affects one in every 300 people. With the diagnosis comes the certainty of a lifetime of insulin injections, made necessary due to the destruction of insulin-producing cells in the pancreas by a misguided immune system.

Insulin is a hormone that alerts the body to the presence of glucose in the blood, typically after a meal. In insulin’s absence, the body’s tissues fail to take up glucose, a key energy source. Without several-times-daily insulin shots, type 1 diabetes patients’ blood sugar levels can shoot up to dangerous heights – a condition called hyperglycemia.

There’s never been any way to prevent type 1 diabetes, although it can be predicted based on the detection of self-targeting antibodies in a blood test. But screening for type 1 diabetes this way hasn’t been particularly useful, because there’s been nothing to be done for patients diagnosed in the asymptomatic phase except wait for them to become hyperglycemic and put them on insulin.

Now, an elaborate mouse study by Stanford immunologist and structural biologist Paul Bollyky, MD, PhD, shows that it might be possible to intervene during the asymptomatic stage of type 1 diabetes – using a pharmaceutical compound that’s been on the global market for more than 40 years and has a terrific safety record – thereby stopping the immune system’s stupid but relentless destruction of the pancreas’s vital insulin-producing cells, and stave off hyperglycemia indefinitely.

Bollyky and his colleagues first showed that a particular substance, hyaluronan, builds up near insulin-producing cells in mice developing the murine equivalent of type 1 diabetes, confirming earlier findings in postmortem human pancreatic tissue that had been supplied to Bollyky’s team by the Juvenile Diabetes Research Foundation.

“We wondered what would happen if we prevented that buildup,” Bollyky told me when I interviewed him for my news release on the study. “And we knew a drug that does that.”

Continue Reading »

Humor, Media, Medicine and Society, Neuroscience, Research, Stanford News

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?


Almost two years ago, in a Scope blog entry titled “Can Joe Six-Pack compete with Sid Cyborg?” I posed the question: “Just how long will it be before we can no longer tell our computers from ourselves?”

I think it’s safe to say we’re not there yet. Either that, or extraterrestrials have been reading my news releases and finding them puzzling.

Last week we put out a news release I’d written about a dramatic discovery by Stanford radiologists Mike Zeineh, MD, PhD, Brian Rutt, PhD, and their colleagues. In brief, they’d analyzed postmortem slabs of brain tissue from people diagnosed with Alzheimer’s, compared them with equivalent brain-tissue slabs taken from people who’d died without any Alzheimer’s-like symptoms, and noticed some striking and intriguing differences. In a key brain region essential to memory formation, Zeineh and Rutt had spotted – only in Alzheimer’s brains, not normal ones – iron deposits engulfed by mobile inflammatory cells. This observation’s potentially big implications were plenty newsworthy.

It so happened that, on the day we issued the release, a high-powered five-day-long meeting on Alzheimer’s sponsored by the eponymous Alzheimer’s Association was in session in Washington, D.C. As a result, many of the brain-oriented science writers to whom my news release was targeted were preoccupied.

I was a little anxious about that. So, the other day, I turned to my favorite search engine to see if the release had managed to get some traction in the popular press. As I’d feared, the Washington conference had sucked up a lot of the oxygen in the earthly neuroscience arena.

But apparently, the release had done better in Outer Space. I saw that it had been picked up by, for example, Red Orbit (a website that I’ve always assumed, based on its name, emanates from Mars).

My eyes were next drawn to a link to an unfamiliar outfit called AZ News, which bills itself in a tagline as an “International Online News Site.” I clicked on the link, and saw a news report with the same title as my release. I started reading the text below.

The first words were: “In autopsy mind hankie from people not diagnosed with Alzheimer’s…” I don’t know what an “autopsy mind hankie” is, but I suspect it’s a mind-blower.

I checked our release. That’s not what I’d written at all. What I’d said was, “In postmortem brain tissue from people not diagnosed with Alzheimer’s…”

It seemed pretty clear that the release had been translated into some language – I had no idea which – and then, for some reason, reverse-translated back into English. I read on.

Continue Reading »

Global Health, HIV/AIDS, Immunology, Research, Stanford News, Women's Health

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

virally infected cellsWhen it comes to immune cells, “it takes all kinds” isn’t too bad a description of what makes for the best composition of our fighting force for warding off viruses, bacteria and incipient tumors. But in a study just published in Science Translational Medicine, Stanford infectious-disease immunologist Catherine Blish, MD, PhD, and her colleagues have found, unexpectedly, that high diversity in the overall population of one particular type of immune cells strongly correlates with an increased likelihood of subsequent infection by HIV.

The investigators had figured that diversity in so-called natural killer cells, or NK cells, would be a strength, not a detriment. “Our hypothesis was wrong,” Blish (much of whose research focuses on NK cells) told me. In this study,  it was higher, rather than lower, diversity in this immune-cell population that turned out to be associated with increased HIV susceptibility.

NK cells, fierce white blood cells that help fight viruses and tumors, harbor various combinations of receptors on their surface. Some receptors recognize signs of our other cells’ normalcy, while others recognize signs that a cell is stressed — due, say, to viral infection or cancerous mutation. On recognizing their targeted features on other cells’ surfaces, an NK cell’s “normalcy” receptors tend to inhibit it, while its stress-recognizing receptors activate it.

All told, NK cells can have many thousands of different combinations of these receptors on their surfaces, with each combination yielding a slightly different overall activation threshold. At birth, our NK cells are pretty similar to one another. But as they acquire life experience – largely from viral exposure, Blish thinks – they increasingly diverge in the specific combinations of receptors they carry on their surfaces.

From my news release on the study:

In order to assess the impact of NK-cell diversity on adult humans’ viral susceptibility, Blish and her associates turned to blood samples that had been drawn during the Mama Salama Study, a longitudinal study of just over 1,300 healthy … Kenyan women. [T]he researchers carried out a precise analysis of NK cells in the women’s blood and observed a strong positive correlation between the diversity of a woman’s NK cell population and her likelihood of becoming infected with HIV.

This correlation held up despite the women’s being statistically indistinguishable with respect to age, marital status, knowledge of sexual partners’ HIV status, history of trading sex for money or goods, sexually transmitted disease status or reported frequency of recent unprotected sex.

And the NK-diversity-dependent difference in these women’s likelihood of HIV infection was huge. From my release:

Those with the most NK-cell diversity were 10 times as likely as those with the least diversity to become infected. A 10-fold risk increase based solely on NK-cell diversity is far from negligible, said Blish. “By way of comparison, having syphilis increases the risk of contracting HIV two- to four-fold, while circumcised men’s HIV risk is reduced by a factor of 2.5 or 3,” she said.

These surprising findings  could spur the development of blood tests capable of predicting individuals’ susceptibility to viral infection.

Previously: Study: Pregnancy causes surprising changes in how the immune system responds to the flu, Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease and Our aging immune systems are still in business, but increasingly thrown out of balance
Photo by NIAID

Imaging, Immunology, Mental Health, Neuroscience, Research, Stanford News

Are iron, and the scavenger cells that eat it, critical links to Alzheimer’s?

Are iron, and the scavenger cells that eat it, critical links to Alzheimer's?

iron linkIf you’ve been riding the Alzheimer’s-research roller-coaster, brace yourself for a new twist on that wrenching disease of old age.

In a study published in Neurobiology of Aging, Stanford radiologists Mike Zeineh, MD, PhD,  and Brian Rutt, PhD, and their colleagues used a ultra-powerful magnetic-resonance-imaging (MRI) system to closely scrutinize postmortem tissue from the brains of people with and without Alzheimer’s disease. In four out of five of the Alzheimer’s brains they looked at, but in none of the five non-Alzheimer’s brains, they found what appear to be iron-containing microglia – specialized scavenger cells in the brain that can sometimes become inflammatory – in a particular part of the hippocampus, a key brain structure that’s absolutely crucial to memory formation as well as spatial orientation and navigation.

Zeineh and Rutt told me they don’t know how the iron gets into brain tissue, or why it accumulates where it does. But iron, which in certain chemical forms can be highly reactive and inflammation-inducing, is ubiquitous throughout the body. Every red blood cell that courses through our microvasculature is filled with it. So one possibility – not yet demonstrated – is that iron deposits in the hippocampus could result from micro-injury to small cerebral blood vessels there.

As surprising as the iron-laden, inflamed microglia Zeineh, Rutt and their associates saw in Alzheimer’s but not normal brains was what they didn’t see. Surprisingly, in the brain region of interest there was no consistent overlap of either iron or microglia with the notorious amyloid plaques that have been long held by many neuroscientists and pharmaceutical companies to be the main cause of the disorder. These plaques are extracellular aggregations of a small protein called beta-amyloid that are prominent in Alheimer’s patients’ brains, as well as in mouse models of the disease.

Because they weren’t able to visualize small, soluble beta-amyloid clusters (now believed to to be the truly toxic form of the protein), Rutt and Zeineh don’t rule out a major role for beta-amyloid in the early developmental stages of pathology in Alzheimer’s.

Continue Reading »

Neuroscience, Research, Science, Stanford News

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

spiral staircase“History,” said Winston Churchill (or was it Arnold Toynbee or Edna St. Vincent Millay?), “is just one damn thing after another.” In many respects, so is good science.

And that’s just how it should be, Stanford neuroscientist and molecular physiologist Tom Südhof, MD, told me a few years ago when I interviewed him for a story I wrote in connection with the Lasker Award, a prestigious prize he’d won shortly before receiving the 2013 Nobel Prize in physiology or medicine:

Asked to recall any defining “eureka!” moments that had catapulted his hunches forward to the status of certainty, Südhof noted that in his experience, science advances step by step, not in jumps. “I believe strongly that most work is incremental,” he said. The systematic solution of highly complex problems requires a long view and plenty of patience.

Climbing a long ladder to the Nobel one small step at a time, Südhof continually raised the power of his conceptual microscope over the decades as he probed the intricate workings of synapses: the all-important junctions in the nervous system where information, in the form of chemical messengers called neurotransmitters, gets passed from one nerve cell to another.

From an explanation of Südhof’s synaptic studies:

The firing patterns of our synapses underwrite our consciousness, emotions and behavior. The simple act of taking a step forward, experiencing a fleeting twinge of regret, recalling an incident from the morning commute or tasting a doughnut requires millions of simultaneous and precise synaptic firing events throughout the brain and peripheral nervous system.

A philosopher might say that synapses collectively constitute the physiological substrate for the soul. A futurist might write (as I once did):

With nanobots monitoring every critical neural connection’s involvement in a thought or emotion or experience, you’ll be able to back up your brain – or even try on someone else’s – by plugging into a virtual-reality jack. The brain bots feed your synapses the appropriate electrical signals and you’re off and running, without necessarily moving.

Continue Reading »

Autoimmune Disease, Immunology, Public Health, Research, Sleep, Stanford News

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

syringesBack in 2001, in the wacko cinematic tour de farce “Rat Race,” British actor Rowan Atkinson – a.k.a. the iconic “Mr. Bean” – put a humorous face on narcolepsy, a rare, chronic, incurable and lifelong sleep disorder that can strike at any time, even in the heat of a foot race.

In 2009, narcolepsy suddenly became, for a time, not quite so rare.

The swine flu pandemic sweeping the world that year was no joke. In the United States alone, the H1N1 strain of influenza virus responsible for that pandemic resulted in 274,304 hospitalizations and 12,469 deaths, as mentioned in our news release on a just-published study in Science Translational Medicine.

There probably would have been far more hospitalizations and deaths had not several vaccines tailored to that particular influenza strain been rushed to the market. Two vaccines in particular — Focetria, manufactured by Novartis, and Pandemrix, made by GlaxoSmithKline — are credited with saving a lot of lives in Europe. But there was a dark side. As our news release notes:

Populations that had been immunized with GlaxoSmithKline’s Pandemrix vaccine showed an increase in narcolepsy, but those immunized with Novartis’ Focetria did not.

That’s not news; it’s been known for some time. But the findings in the new study, whose senior author is Stanford neuroimmunologist Larry Steinman, MD, may explain why.

Continue Reading »

Aging, Cancer, Dermatology, Genetics, Research, Stanford News

Genetic secrets of youthful skin

Genetic secrets of youthful skin

new hatEvery year, upwards of $140 billion a year gets spent on cosmetics. In the United States alone, says an authoritative report, a recent year saw upwards of 5.6 million Botox procedures, 1.1 million chemical peels, almost a half-million laser skin procedures, 196,286 eyelid surgeries and a whole bunch of face lifts.

If you’ve got the courage to compare your present-tense face with the one you were wearing 20 or even 10 years ago, you’ll see why. As I wrote in a just-published Stanford Medicine article, “Wither youth?”:

The terrain of aging skin grows all too familiar with the passing years: bags under the eyes, crow’s feet, jowls, tiny tangles of blood vessels, ever more pronounced pores and pits and pigmentation irregularities. Then there are wrinkles — long, deep “frown lines” radiating upward from the inside edges of the eyebrows and “laugh lines” that trace a furrow from our nostrils to the edges of our lips in our 40s, and finer lines that start crisscrossing our faces in our 50s. Sagging skin gets more prominent in our later years as we lose bone and fat.

“And,” I added wistfully, “it’s all right there on the very outside of us, where everyone else can see it.”

Stanford dermatologist Anne Chang, MD, who sees a whole lot of skin, got to wondering: Why does skin grow old? Armed with a sophisticated understanding of genetics, she went beyond lamenting lost youth and resolved to address the question scientifically, asking: “Can you turn back time? Can aging effects be reversed? Can you rejuvenate skin, make it young again?”

The answers she’s come up with so far – from hereditary factors to a possible underlying genetic basis for how some treatments now in common commercial cosmetic use (such as broadband light therapy) could potentially slow or even reverse the aging of skin – are described in my magazine article.

Previously: This summer’s Stanford Medicine magazine shows some skinResearchers identify genetic basis for rosacea, New study: Genes may affect skin youthfulness and Aging research comes of age
Photo by thepeachpeddler

Cancer, Imaging, Research, Stanford News, Surgery

Better tumor-imaging contrast agent: the surgical equivalent of “cut along dotted line”?

cut horseIt would be tough for most people to take a snubbed-nose scissors to an 8-1/2″ x 11″ sheet of blank paper and carve out a perfect silhouette of, say, a horse from scratch. But any kid can be an artist if it means merely cutting along a boundary separating two zones of different colors.

Tumor-excision surgery requires an artist’s touch. It can be tough to distinguish cancerous from healthy tissues, yet the surgeon needs to approach perfection in precisely removing every possible trace of the tumor while leaving as much healthy tissue intact as possible. To help surgeons out, technologists have been designing contrast agents that target only tumor cells, thus providing at least a dotted line for scalpel wielders.

Stanford pathologist and molecular-probe designer Matthew Bogyo, PhD, in a study published in ACS Chemical Biology, has now demonstrated, using mouse models of breast, lung and colon cancer, the effectiveness of a fluorescence-emitting optical contrast agent that selectively accumulates in tumors and can be used to guide surgery. In effect, the probe lights up the tumor, providing a convenient, high-resolution dotted line for its excision.

Perhaps more striking, the new study showed that this probe, designed by Bogyo’s group, is compatible with a robotic remote minimally invasive surgery system that is already enjoying widespread commercial use. Intuitive Surgical, Inc., the company that sells this system, collaborated on the study.

Previously: Stanford researchers explore new ways of identifying colon cancer, Cat guts, car crashes, and warp-speed Toxoplasma infections and Compound clogs Plasmodium’s in-house garbage disposal, hitting malaria parasite where it hurts
Photo by Merryl Zorza

Stanford Medicine Resources: