Published by
Stanford Medicine

Category

Science

Behavioral Science, In the News, Research, Science

“Benign masochism” motivates common strange behaviors

"Benign masochism" motivates common strange behaviors

14674431439_be72558bd3_zI can recall many times I’ve offered something to a friend saying, “Smell this, it’s disgusting!” And more than once, the friend obliged. According to a National Geographic blog piece, the psychological motivation behind the appeal of stinky things is the same as the appeal of roller coasters, painfully spicy foods, and deep tissue massage. Likewise with reading sad novels or watching scary movies (though this last one is not something I personally enjoy). So what’s the common thread?

“Benign masochism,” a term coined by Paul Rozin, PhD, professor emeritus of psychology at the University of Pennsylvania, describes how humans enjoy negative sensations and emotions when they’re reassured that no harm will come to them. A “safe threat,” in other words.

The blog post is centered on our enjoyment of disgust, inspired by the massive audience at a recent blooming of a corpse flower at UC Berkeley’s Botanical Gardens. Valerie Curtis, PhD, a research director at the London School of Hygiene and Tropical Medicine and Psychology Today’sDisgustologist“, is quoted as saying the phenomenon is not dissimilar from kids playing war games in which they can “practice” their reactions to unpleasant situations.

“The ‘play’ motive leads humans (and most mammals, especially young ones) to try out experiences in relative safety, so as to be better equipped to deal with them when they meet them for real,” she says. “We are motivated to find out what a corpse smells like and see how we’d react if we met one.” Gross!

Previously: Looks of fear and disgust help us see threats, study shows
Photo by Dave Pape

Health Disparities, Medical Education, Medicine and Society, Public Health, Science

Stanford Medical Youth Science Program for underrepresented students expands and deepens

Stanford Medical Youth Science Program for underrepresented students expands and deepens

unnamedThe Stanford Medical Youth Science Program (SMYSP) is a 5-week summer residential program for rising high school juniors and seniors interested in science and medicine. The students, who come from underrepresented and low-income backgrounds, have an opportunity to experience the medical profession from the inside out. This year’s program concluded late last month with a graduation ceremony in which the students presented their scientific research projects on health disparities and advocacy to an audience of their parents and supporters.

A few weeks ago, I had the chance to speak with the program’s longtime director, Judith T. Ned, EdD, who told me SMYSP has come a long way since it was co-founded 28 years ago by Stanford epidemiologist Marilyn Winkleby, PhD, MPH. This is Ned’s 14th year running the show. She has made lot of beneficial changes and expansions, many of which happened since we last featured SMYSP in 2010, without losing sight of the program’s purpose: to expose these kids to the fields of science and medicine while increasing workforce diversity in the health professions.

Each year, 12 boys and 12 girls are selected for the program, all of whom come from 20 counties surrounding Stanford. “The goal is to really provide services and opportunities to students who are in our backyard, if you will,” Ned told me. The students have a well-rounded curriculum – not only do they attend lectures by leading academics and industry professionals, anatomy lectures and labs (with cadavers!), and twice-weekly clinical internships, but they have non-clinical days where they investigate departments like hospital food service, security, and art therapy. “We want to show them that it takes multiple people in multiple areas to really make the hospital function. Most of the time, many of my students serve as translators for their parents when they go into the hospital. This is the flip side: the provider’s perspective, not the patient’s. It’s been an interesting experience to see them switch mindsets.”

Programming includes SAT prep, “game shows” to improve knowledge retention, and evening workshops that include leadership development and performing arts. Ned wants the students to know that “you can take a well-rounded liberal arts education, get into medical school, and still practice your craft, embracing both sides of your identity.” Community service is also a key feature of the program, such as the beautification project they did at the East Palo Alto YMCA the Saturday before our interview.

Continue Reading »

Autoimmune Disease, Genetics, Immunology, Science, Stanford News, Technology

Women and men’s immune system genes operate differently, Stanford study shows

Women and men's immune system genes operate differently, Stanford study shows

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes connected with the immune system switch on and off more frequently than other genes, and those same genes operate differently in women and men. What’s more, the differences in gene activity are mostly not genetic.

A couple of years ago, geneticists Howard Chang, MD, PhD; Will Greenleaf, PhD, and others at Stanford invented a way to map the epigenome – essentially the real time on/off status of each of the 22,000 genes in our cells, along with the switches that control whether each gene is on or off.

Imagine a fancy office vending machine that can dispense 22,000 different drinks and other food items. Some selections are forever pumping out product; other choices are semi permanently unavailable. Still others dispense espresso, a double espresso or hot tea depending on which buttons you push. The activity of the 22,000 genes that make up our genomes are regulated in much the same way.

That’s a lot to keep track of. But Chang and Greenleaf’s technology, called ATAC-seq, makes it almost easy to map all that gene activity in living people as they go about their lives. Their latest study, published in Cell Systems, showed that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases, and also that men and women use different switches for many immune system genes. That sex-based difference in activity might explain the much higher incidence of autoimmune diseases in women — diseases like multiple sclerosis, lupus and rheumatoid arthritis.

The team took ordinary blood samples from 12 healthy volunteers and extracted immune cells called T cells. T cells are easy to isolate from a standard blood test and an important component of the immune system. With T cells in hand, the team looked at how certain genes are switched on and off, and how that pattern varied from individual to individual. Chang’s team also looked at how much change occurred from one blood draw to the next in each volunteer.

Chang told me, “We were interested in exploring the landscape of gene regulation directly from live people and look at differences. We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.”

Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he said.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using
Photo by Baraka Office Support Services

Imaging, Microbiology, Research, Science, Stanford News, Technology

3-D structure of key signaling protein and receptor revealed

3-D structure of key signaling protein and receptor revealed

Using ultra-bright X-rays at SLAC National Accelerator Laboratory, a team of international researchers has captured the 3-D structure of a key signaling protein and its receptor for the first time.

The discovery provides new insight into the functioning of a common cell receptor called a G protein-coupled receptor or GPCR. Researchers estimate this protein, and its relatives, are the targets of about 40 percent of pharmaceuticals. From a SLAC release:

“This work has tremendous therapeutic implications,” said Jeffrey Benovic, PhD, a biochemist who was not involved with the study. “The study is a critical first step and provides key insight into the structural interactions in these protein complexes.”

Specifically, the researchers were able to illuminate the structure of the GPCR bonded with a signaling protein called arrestin. Arrestins and G proteins both dock with the GPCRs, however, researchers had previously only examined a bonded G protein. G proteins are generally the “on” switch, while arrestins usually signal the GPCR to turn off:

Many of the available drugs that activate or deactivate GPCRs block both G proteins and arrestins from docking.

“The new paradigm in drug discovery is that you want to find this selective pathway – how to activate either the arrestin pathway or the G-protein pathway but not both — for a better effect,” said Eric Xu, PhD, a scientist at the Van Andel Research Institute in Michigan who led the experiment. The study notes that a wide range of drugs would likely be more effective and have fewer side effects with this selective activation.

Previously: Why Stanford Nobel Prize winner Brian Kobilka is a “tour de force of science”, Funding basic science leads to clinical discoveries, eventually and Video of Brian Kobilka’s Nobel lecture
Video by SLAC National Accelerator Laboratory

Ethics, In the News, Medicine and Society, Science, Science Policy, Sports, Stanford News

Stanford expert celebrates decision stopping testosterone testing in women’s sports

Stanford expert celebrates decision stopping testosterone testing in women's sports

Female track and field athletes no longer need to have their natural testosterone levels below a certain threshold to compete in international events, the so-called “Supreme Court of sports”, the Court of Arbitration for Sport, ruled Monday.

Katrina Karkazis, PhD, a Stanford senior research scholar who was closely involved with the case, got the news on Friday, while she was in a San Francisco dog park. “What a day!” she said. “I was madly refreshing my email — I thought we were going to lose… I just started screaming and crying.”

Karkazis, who is an expert on ethics in sports and also gender, said she spent a year of her life working on the case.

She served as an advisor to 19-year-old sprinter Dutee Chand, who challenged the regulation that female athletes must have certain testosterone levels or undergo medical interventions to lower their testosterone to be allowed to compete against women in events governed by the International Association of Athletics Federations (IAAF), the international regulatory body of track and field.

The ruling suspends the IAAF’s testing regimen for two years, but Karkazis expects the decision will lead to permanent changes in women’s sports, including a reevalution by the International Olympic Committee.

“I’m thrilled,” Karkazis said. She said she was also surprised. “I didn’t think it was our time. I thought there were still too many entrenched ideas about testosterone being a ‘male hormone’ and it not belonging in women.”

Karkazis gained international attention after penning an op-ed in The New York Times in 2012 when the IAAF and the International Olympic Committee crafted a new policy banning women with naturally high levels of testosterone from competing.

“You can’t test for sex,” Karkazis said. “It’s impossible. There’s no one trait you can look at to classify people. There are many traits and there are always exceptions.”

She said that now women who have lived and competed their entire lives as women will be eligible to compete, a default policy she believes is sufficient to ensure a level playing field.

Previously: “Drastic, unnecessary and irreversible medical interventions” imposed upon some female athletes, Arguing against sex testing in athletes and Is the International Olympic Committee’s policy governing sex verification fair?
Photo by William Warby

Cancer, Genetics, Research, Science, Stanford News

Using CRISPR to investigate pancreatic cancer

Using CRISPR to investigate pancreatic cancer

dna-154743_1280Writing about pancreatic cancer always gives me a pang. My grandmother died from the disease over 30 years ago, but I still remember the anguish of her diagnosis and the years of chemotherapy and surgery she endured before her death. This disease is much more personal to me than many I cover.

Unfortunately, survival rates haven’t really budged since I was in high school, in part because the disease is often not diagnosed until it’s well established. As geneticist  Monte Winslow, PhD, described to me in an email:

Pancreatic cancer is very common and almost uniformly fatal. Human pancreatic cancers usually have many mutations in many different genes but we know very little about how most of them drive pancreatic cancer initiation, development, and progression. Recreating these cancer-causing mutations in cells of the mouse pancreas can generate tumors that look and behave very similarly to human pancreas cancer.

Unfortunately, traditional methods used to generate mouse models of human cancer are very time-consuming and costly.

Winslow, along with postdoctoral scholar Shin-Heng Chiou, PhD, and graduate student Ian Winters, turned to the latest darling of the biochemistry world — the gene-editing system known as CRISPR — to devise a way to quickly and efficiently turn off genes implicated in the development of pancreatic cancer in laboratory mice. Their work will be featured on the cover of Genes and Development on Monday. As Winslow described:

Our goal was use CRISPR/Cas9 genome editing to make altering a gene of interest in pancreas cancer simple and fast. Shin-Heng and Ian worked together to develop novel tools and bring them together to generate this new system that we hope will dramatically accelerate our understanding of pancreas cancer. The increased basic understanding of how this cancer works may ultimately lead to better therapies for patients.

Continue Reading »

Big data, Cancer, Genetics, Immunology, Research, Science, Stanford News

Linking cancer gene expression with survival rates, Stanford researchers bring “big data” into the clinic

Linking cancer gene expression with survival rates, Stanford researchers bring "big data" into the clinic

Magic 8 ball“What’s my prognosis?” is a question that’s likely on the mind, and lips, of nearly every person newly diagnosed with any form of cancer. But, with a few exceptions, there’s still not a good way for clinicians to answer. Every tumor is highly individual, and it’s difficult to identify anything more than general trends with regard to the type and stage of the tumor.

Now, hematologist and oncologist Ash Alizadeh, MD, PhD; radiologist Sylvia Plevritis, PhD; postdoctoral scholar Aaron Newman, PhD; and senior research scientist Andrew Gentles, PhD, have created a database that links the gene-expression patterns of individual cancers of 39 types with the survival data of the more than 18,000 patients from whom they were isolated. The researchers hope that the resource, which they’ve termed PRECOG, for “prediction of cancer outcomes from genomic profiles” will provide a better understanding of why some cancer patients do well, and some do poorly. Their research was published today in Nature Medicine.

As I describe in our release:

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. By doing so, it may be possible to learn what has gone wrong in the cancer cells, and give ideas as to how best to block the cells’ destructive growth. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

Instead, the researchers pulled back and sought patterns that might become clear only when many types of cancers, and thousands of patients were lumped together for study:

Gentles and Alizadeh first collected publicly available data on gene expression patterns of many types of cancers. They then painstakingly matched the gene expression profiles with clinical information about the patients, including their age, disease status and how long they survived after diagnosis. Together with Newman, they combined the studies into a final database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” said Alizadeh. “Then we could ask what we could learn more broadly.”

The researchers found that they were able to identify key molecular pathways that could stratify survival across many cancer types:

In particular, [they] found that high expression of a gene called FOXM1, which is involved in cell growth, was associated with a poor prognosis across multiple cancers, while the expression of the KLRB1 gene, which modulates the body’s immune response to cancer, seemed to confer a protective effect.

Alizadeh and Plevritis are both members of the Stanford Cancer Institute.

Previously: What is big data?Identifying relapse in lymphoma patients with circulating tumor DNA,  Smoking gun or hit-and-run? How oncogenes make good cells go bad and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Photo by CRASH:candy

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 »

Dermatology, Evolution, Pediatrics, Research, Science, Stanford News, Surgery

To boldly go into a scar-free future: Stanford researchers tackle wound healing

To boldly go into a scar-free future: Stanford researchers tackle wound healing

scarshipAs I’ve written about here before, Stanford scientists Michael Longaker, MD, and Irving Weissman, MD, are eager to find a way to minimize the scarring that arises after surgery or skin trauma. I profiled the work again in the latest issue of Stanford Medicine magazine, which focuses on all aspects of skin health.

My story, called “Scarship Enterprise,” discusses how scarring may have evolved to fulfill early humans’ need for speed in a cutthroat world:

“We are the only species that heals with a pathological scar, called a keloid, which can overgrow the site of the original wound,” says Longaker. “Humans are a tight-skinned species, and scarring is a late evolutionary event that probably arose in response to a need, as hunter-gatherers, to heal quickly to avoid infection or detection by predators. We’ve evolved for speedy repair.”

Check out the piece if you’re interested in reading more about this or learning how scarring happens, or why, prior to the third trimester, fetuses heal flawlessly after surgery. (Surprisingly, at least to me, many animals also heal without scarring!)

Previously: This summer’s Stanford Medicine magazine shows some skinWill scars become a thing of the past? Stanford scientists identify cellular culprit, New medicine? A look at advances in wound healing and Stanford-developed device shown to reduce the size of existing scars in clinical trial
Illustration by Matt Bandsuch

Applied Biotechnology, Big data, Cancer, Genetics, Research, Science, Stanford News

Peeking into the genome of a deadly cancer pinpoints possible new treatment

Peeking into the genome of a deadly cancer pinpoints possible new treatment

small cell lung cancerSmall cell lung cancer is one of the most deadly kinds of cancers. Typically this aggressive disease is diagnosed fairly late in its course, and the survival rates are so dismal that doctors are reluctant to even subject the patient to surgery to remove the tumor for study. As a result, little is known about the molecular causes of this type of cancer, and no new treatments have been approved by the Food and Drug Administration since 1995.

Now a massive collaboration among researchers around the world, including the University of Cologne in Germany and Stanford, has resulted in the collection of more than 100 human small cell lung cancer tumors. Researchers sequenced the genomes of the tumors and identified some key steps in their development. They also found a potential new weak link for treatment.

The findings were published today in Nature, and Stanford cancer researcher Julien Sage, PhD, one of three co-senior authors of the paper, provided some details in an email:

With this larger number of specimens analyzed, a more detailed picture of the mutations that contribute to the development of small cell lung cancer now emerges. These studies confirmed what was suspected before, that loss of function of the two tumor suppressor genes, Rb and p53, is required for tumor initiation. Importantly, these analyses also identified new therapeutic targets.

The researchers also saw that, in about 25 percent of cases, the Notch protein receptor was also mutated. This protein sits on the surface of a cell; when Notch binds, it initiates a cascade of signaling events within the cell to control its development and growth. As Sage explained:

The mutations in the Notch recepetor were indicative of loss of function, suggesting that Notch normally suppresses small cell lung cancer development. Indeed, when graduate student Jing Lim in my lab activated Notch in mice genetically engineered to develop small cell lung cancer, we found a potent suppression of tumor development. These data identify the Notch signaling pathway as a novel therapeutic target in a cancer type for which new therapies are critically needed.

This is not Sage’s first foray into fighting small cell lung cancer. In 2013, he collaborated with other researchers at Stanford, including oncologist Joel Neal, MD, PhD, to identify a class of antidepressants as a possible therapy for the disease.

Previously: Gene-sequencing rare tumors – and what it means for cancer research and treatment, Listening in on the Ras pathway identifies new target for cancer therapy and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Image by Yale Rosen

Stanford Medicine Resources: