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Stanford Medicine

Applied Biotechnology, Clinical Trials, FDA, Research, Stanford News

An inside look at drug development

An inside look at drug development

B0008664 Assorted pills, tablets and capsules

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

A recently published book, A Practical Guide to Drug Development in Academia, crystallizes the sessions. Even if you’re not a scientist dreaming of curing cancer with your latest discovery, you might find it interesting.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development and Accelerating the translation of biomedical research into clinical applications.
Photograph from Wellcome Images

Medical Education, Medical Schools, Stanford News, Surgery

After work, a Stanford surgeon brings stones to life

After work, a Stanford surgeon brings stones to life

MA15_Profs_Greco_480pxClassrooms, research, grant writing, faculty meetings… It can be easy to forget that professors have a life outside of the classroom, perhaps with surprising hobbies and talents. The new issue of Stanford Magazine highlights the extra-professional lives of some of the university’s extraordinary professors, including Ralph Greco, MD.

Greco is a sculptor of stone as well as a surgeon. His work decorates his home and has sold for as much as $8,500. Perhaps his most notable sculpture is the abstract “S” that graces the Department of Surgery. He created the work of art from a 400-pound marble boulder that was gifted to him at a graduation dinner when he was the director of the general surgery residency program.

It’s perhaps not surprising that the multi-faceted Greco is an advocate for work-life balance among surgeons. He established a support program after the suicide of a surgical resident, and because he says sculpting can be “too self centered,” he pursues other interests as well. Check out the article to learn more.

Previously: Program for residents reflects “massive change” in surgeon mentality and New surgeons take time out for mental health
Photo by Nicolo Sertorio

Global Health, Mental Health, Research, Stanford News

Study explores how cultural differences can shape the way we respond to suffering

Study explores how cultural differences can shape the way we respond to suffering

8909380232_a647e15c23_zOur emotions may be a deeply personal experience, but the way we perceive and express our feelings may not be as unique – or random – as we think. According to recent research, culture influences the way some Americans and Germans convey their mood. If this is universally true, it could mean that people of the same culture tend to express their feelings in similar ways.

As this Stanford Report story explains, researchers Jeanne Tsai, PhD, an associate professor of psychology, and Birgit Koopmann-Holm, PhD, a German citizen who earned her doctorate in Tsai’s lab, noticed that Americans of European decent and Germans seemed to differ in the way they express feelings of sympathy:

Americans tend to emphasize the positive when faced with tragedy or life-threatening situations. American culture arguably considers negativity, complaining and pessimism as somewhat “sinful,” [Tsai] added.

Unlike when Americans talk about illness, Germans primarily focus on the negative, Tsai and Koopmann-Holm wrote. For example, the “Sturm und Drang” (“Storm and Drive”) literary and musical movement in 18th-century Germany went beyond merely accepting negative emotions to actually glorifying them.

This seemingly simple observation could have important societal implications, the researchers explain: Studies show that empathy affects our willingness to help someone who is suffering. But, as noted in the article, “until now, Tsai said, no studies have specifically examined how culture shapes ‘different ways in which sympathy, compassion or other feelings of concern for another’s suffering might be expressed.'”

In their study (subscription required, pdf here), published in the Journal of Personality and Social Psychology, the researchers conducted four separate experiments on 525 undergraduate students in the U.S. and Germany to see if Americans accentuate the positive more than Germans do when expressing their condolences. The students were asked how they would feel in a variety of hypothetical situations (such as a scenario where a friend lost a loved one), what feelings they would want to avoid and how they would select and rate sympathy cards.
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Evolution, Global Health, In the News, Microbiology, Nutrition, Research

A key bacteria from hunter gatherers’ guts is missing in industrial societies, study shows

392924423_860dafa0a4_oTrends like the paleo diet and probiotic supplements attest to the popular idea that in industrial societies, our digestion has taken a turn for the worse. The scientific community is gathering evidence on how the overuse of antibiotics affects our microbiome, and on what might be causing the increasing incidence gastrointestinal inflammatory disorders like Crohn’s disease and colitis. Scientists are now one step closer to knowing exactly what has changed since the majority of humans were hunter-gatherers.

Yesterday, a paper published in Nature Communications found that an entire genus of bacteria has gone missing from industrialized guts. Treponema are common in all hunter-gatherer societies that have been studied, as well as in non-human primates and other mammals. Treponema have primarily been known as pathogens responsible for diseases like syphilis, but the numerous strains found in the study are non-pathenogenic and closely resemble carbohydrate-digesting bacteria in pigs, whose digestive system is notably similar to that of humans. The genus is undetectable in humans from urban-industrial societies.

The study, led by anthropologists from the University of Oklahoma and the Universidad Científica del Sur in Peru, used genomic reconstruction to compare microbes in stool samples from two groups in Peru, one of hunter-gatherers and one of traditional farmers, with samples from people in Oklahoma. Each group comprised around 25 people. This is the first comprehensive study of the full-spectrum of microbial diversity in the guts of a group of hunter-gatherers – in this case, the Amazonian Matses people.

The researchers also sought to understand how diet affects gut health: The hunter-gatherers ate game and wild tubers, the traditional farmers ate potatoes and domestic mammals, and the Oklahomans ate primarily processed, canned, and pre-packaged food, with some additional meat and cheese.

Science published a news report discussing the findings, in which co-author Christina Warinner, PhD, an anthropologist at the University of Oklahoma, is quoted as saying:

Suddenly a picture is emerging that Treponema was part of core ancestral biome. What’s really striking is it is absolutely absent, not detectable in industrialized human populations… What’s starting to come into focus is that having a diverse gut microbiome is critical to maintaining versatility and resiliency in the gut. Once you start to lose the diversity, it may be a risk factor of inflammation and other problems.

Further research is needed to answer the next question: Is there a direct link between the absence of Treponema and the digestive health and prevalence of certain diseases (like colitis and Crohn’s) in industrialized humans? If so, this could be a valuable key to increasing our digestive health. It would also indicate that imitating a paleo diet is not enough to achieve a real “paleo gut.”

Previously: Drugs for bugs: industry seeks small molecules to target, tweak, and tune-up our gut microbes, Tiny hitchhikers, big impact: studying the microbiome to learn about disease, Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?, Stanford team awarded NIH Human Microbiome Project grant, and Contemplating how our human microbiome influences personal health
Photo by AJC1

Global Health, Haiti, Infectious Disease, Public Health, Technology

A sanitation solution: Stanford students introduce dry toilets in Haiti

A sanitation solution: Stanford students introduce dry toilets in Haiti

sanitation-toilet-movedIn the United States, we often take for granted the relationship between health and sanitation. Not so in Haiti, where some people dispose of their feces in plastic bags they throw into waterways. As a result, waterborne diseases like cholera are common.

But what’s to be done? Flush toilets guzzle gallons of water and depend on an entire sewage system — an unfeasible option in many developing nations. To fill the gap, a pair of Stanford civil and environmental engineering graduate students have developed a program called re.source, which provides dry household toilets, and empties them for about $5 a month.

From a recent Stanford News story:

Unlike most sanitation solutions that only address one part of a dysfunctional supply chain, container-based sanitation models, such as the re.source service, tackle the whole sanitation chain. The re.source toilets separate solid and liquid waste into sealable containers, and dispense a cover material made of crushed peanut shells and sugarcane fibers that eliminates odors and insect infestations. The solid waste is regularly removed by a service, which takes it to a disposal or processing site to be converted to compost and sold to agricultural businesses.

The re.source students — Kory Russel and Sebastien Tilmans — work under the guidance of Jenna Davis, PhD, an associate professor of civil and environmental engineering. They started small, with a free pilot phase in 130 households in a Haitian slum, but the service has expanded to include 300 additional households with plans to introduce a service in the capital, Port-au-Prince.

The project is part of a larger Stanford focus on water issues ranging from safe drinking water to environmental concerns.

Previously: Waste not, want not, say global sanitation innovators, Stanford pump project makes clean water no longer a pipe dream and Award-winning Stanford documentary to air on PBS tonight
Photo by Rob Jordan

Biomed Bites, Cancer, Genetics, Research, Science, Videos

From finches to cancer: A Stanford researcher explores the role of evolution in disease

From finches to cancer: A Stanford researcher explores the role of evolution in disease

Welcome to Biomed Bites, a feature that appears each Thursday and introduces readers to some of Stanford’s most innovative researchers.

My parents just returned from the trip of a lifetime to the Galapagos. I would have loved to go along — I really dig tortoises, which abound on the islands; my parents even saw a pair mating! And, ever since I took an introductory class on evolution as an undergrad, I’ve longed to visit the spot that was central in Darwin’s postulation of the theory of evolution and natural selection.

No famous finches for me though — I just toiled away behind my computer in northern California. But that doesn’t mean evolution is only happening in another hemisphere. Far from it: Just down the street in the lab of Gavin Sherlock, PhD, experiments are ongoing to elucidate evolution’s fundamental processes.

Sherlock shares his views role of evolution in disease in the video above:

The evolutionary process underlies many disease mechanisms. One such example is cancer, which recapitulates the evolutionary process as mutation occur and then get selected within the tumor. In addition, treatments with chemotherapy may select particular mutations within the tumor itself.

Resistance to antibiotics is also driven by evolution, Sherlock points out. With a deeper understanding, researchers will be better able to combat cancer and craft more effective antibiotics — no international travel required.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Bubble, bubble, toil and trouble — yeast dynasties give up their secrets, Get sloshed, have sex? Wine-making has promoted a frenzy of indiscriminate mating in baker’s yeast, according to Stanford researchers and Computing our evolution

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Following the heart and the mind in biodesign

Following the heart and the mind in biodesign

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

15125593898_7ee05d0a60_zWhen I showed up to meet with the Biodesign fellows, Debayan Saha greeted me by saying, “We are arguing – please join us.”

The source of the argument turned out to be a thorny one. The team had previously attended cardiovascular disease clinics and from those visits identified more than 300 possible needs that, if addressed, might improve patient care.

Now, their job was to narrow down those 300+ needs to the one they would eventually develop a prototype device to address.

Part of the process Stanford Biodesign fellows learn is a rigorous method for identifying medical needs that also make business sense to address. The first step: eliminate the duds.

In this round, the each team member had individually rated the needs according to their individual levels of interest on a scale of 1 to 4. That interest could reflect the fact that they think the technology is interesting, or the fact that the need is one they would be excited about addressing.

Now they were trying to rate the needs on the same 1 to 4 scale according to the number of people who would benefit if it were addressed. The combination of these two ratings—one subjective and the other objective—would produce a shorter list of needs that were both of interest to the fellows and would benefit enough people that any future company could be successful

That objective rating was the source of the polite disagreement I had walked into. As one example, if a particular need applied to people who had a stroke, should they assume that all people who have had a stroke would benefit from a solution (giving the need a higher rating of 4), or would only a small subset benefit (giving the need a lower rating of 1 or 2)?

By and large Harsh Sheth, MD, leaned toward 4s while Shashi Ranjan, PhD, leaned toward 2s. Saha mostly just leaned back. Much discussion ensued.

In the end the team managed to assign a single score indicating the number of people represented by each need. When combined with their subjective scores, the group was able to eliminate the lowest scoring needs and reduce the list to a mere 133.

One interesting thing I learned is that this careful rubric is harder to apply in India, where good numbers about how many people have particular conditions are harder to come by. Ranjan told me that even in India they would likely use U.S. numbers for some conditions and just scale up to the Indian population. I mentally added this lack of good data to the list of reasons Stanford-India Biodesign Program executive director (U.S.) Rajiv Doshi, MD, told me that biodesign is more challenging in India.

Previously: Writing a “very specific sentence” is critical for good biodesign and Good medical technology starts with patients’ needs
Photo by Yasmeen

Global Health, In the News, Mental Health, Public Health, Research

Study links air pollution with anxiety; calls it a “leading global health concern”

Study links air pollution with anxiety;  calls it a "leading global health concern"

3280739522_c1f8001000_zI often find that natural spaces and fresh air have a calming, balancing effect, and judging by the cultural association between relaxation and the outdoors, I’m not alone. Now some new research backs up the connection. Yesterday, the British Medical Journal published an article linking air pollution with anxiety, as well as an editorial on air pollution’s health effects and another study elaborating on a previously-noted connection between pollution and stroke.

The anxiety study, conducted by researchers at Harvard and Johns Hopkins University, showed a significant connection between exposure to fine particulate pollution and symptoms of anxiety for more than 70,000 older women (mean age of 70 years) in the contiguous United States. Bigger particles appeared to have no effects, interestingly, nor did living close to a major road. The connection was present over a variety of time periods from one month to fifteen years, but was stronger in the short term. This evidence shows a clear need for studies to be done in other demographic groups, and to elaborate on the biological plausibility of the connection.

The stroke article, meanwhile, is a meta-analysis of 103 studies conducted in 28 countries and including 6.2 million events. Researchers found that both gaseous and particulate air pollution had a “marked and close temporal association” with strokes resulting in hospital admissions or death.

As stated in the editorial, particulate air pollution has already been shown to be a contributing factor in a variety of serious health conditions, including a well-supported link to cardiopulmonary diseases, but also diabetes, low birth weight, and pre-term birth. In fact, the World Health Organization estimates that one of every eight deaths is caused by air pollution. The body of research on the topic suggests that pollution may initiate systemic inflammation, thereby affecting multiple organ systems.

With such a broad range of detrimental effects, and because it affects such a significant percentage of the population, air pollution is becoming a top public health concern. As the University of British Columbia’s Michael Brauer, ScD, wrote in the editorial:

The findings of these two studies support a sharper focus on air pollution as a leading global health concern… One of the unique features of air pollution as a risk factor for disease is that exposure to air pollution is almost universal. While this is a primary reason for the large disease burden attributable to outdoor air pollution, it also follows that even modest reductions in pollution could have widespread benefits throughout populations. The two linked papers in this issue confirm the urgent need to manage air pollution globally as a cause of ill health and offer the promise that reducing pollution could be a cost effective way to reduce the large burden of disease from both stroke and poor mental health.

Photo by Billy Wilson

Cancer, Global Health, Patient Care, Stanford News

New global cancer map aims to improve care in developing countries

New global cancer map aims to improve care in developing countries

cancer map2

Most people don’t associate cancer with the developing world, yet 60 percent of new cancer cases and 70 percent of cancer deaths occur in less developed parts of the world, according to the World Health Organization. Now, the nonprofit Global Oncology, Inc. has launched a Global Cancer Project Map, a first-of-its-kind resource that will connect cancer experts around the world in an effort to advance cancer research and care in low-resource areas.

The interactive map includes more than 800 projects on six continents. With a few simple clicks, users can search for cancer experts and research projects and then contact the investigators and program managers. The goal is to spur collaboration among people in the field and enable experts to share their collective knowledge.

“Before it was difficult or often impossible to find information about cancer projects or experts, especially in limited-resource settings,” said Ami S. Bhatt, MD, PhD, an assistant professor of medicine and genetics at Stanford and co-founder of Global Oncology, Inc. “The map now makes it possible to connect colleagues in the global cancer community with a maximum of six clicks of a computer mouse.”

Bhatt, who directs global oncology for Stanford’s Center for Innovation in Global Health, and GO co-founder Franklin Huang, MD, PhD, have been working with the National Cancer Institute on ways to bring multidisciplinary teams together to solve complex problems in cancer. While there are many dedicated scientists and caregivers doing innovative work in cancer in the developing world, there’s been no single place where they could share knowledge or reference the work of their colleagues, she said. The cancer map is a first step in this process.

“We have the ambitious goal of providing access to every cancer research, care and outreach program in the world through the map,” said Huang, who is an instructor at the Dana-Farber Cancer Institute.

A collaboration with the NCI, the map was developed by GO volunteers, who are scientists, policymakers, public health experts, lawyers and other highly skilled individuals. It covers a wide range of projects, from prevention and screening to clinical programs and palliative care. For instance, it includes a project in Turkey to improve diagnostic accuracy of mammograms to detect breast cancer; development of an early screening test for gastric cancer in Mexico; and use of supplements to prevent arsenic-induced skin cancer in Bangladesh.

“The map is an important and innovative step forward in our effort to reduce health disparities and strengthen human capital in underserved areas of the world,” said Michele Barry, MD, director of Stanford’s Center for Innovation in Global Health. “With cancer rates rapidly increasing in low-resource settings, the map creates a place where the global cancer community can share and access information that is critical to providing better treatment and care.”

Bhatt and Huang unveiled the new map today at the Symposium on Global Cancer Research, being held in Boston. The symposium is co-sponsored by the NCI, the Consortium of Universities for Global Health and the Dana-Farber Cancer Institute.

Image from Global Oncology, Inc.

Aging, Genetics, Research, Science, Stanford News

“Are we there yet?” Exploring the promise, and the hype, of longevity research

"Are we there yet?" Exploring the promise, and the hype, of longevity research

Brunet photoThe days are getting longer, and it’s no longer dark outside when I drop my teenager at school for her early-bird class. I appreciate the light, of course, and there’s something soothing about the rhythmic change of seasons.

If only we could extend our lifespan in a similar gentle, reliable manner.

The idea of living longer, and healthier, is the theme of my story for the new issue of Stanford Medicine magazine. It’s my favorite kind of article – a dash of juicy science history, a panoply of dedicated scientists and a brand-new animal model (and my newest crush) that may open all kinds of research doors. Best of all, there’s a sense of real progress in the field. From my article:

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics and newbie fish keeper Anne Brunet, PhD. Brunet, who is an associate director of Stanford’s Paul F. Glenn Center for the Biology of Aging, focuses her research on genes that control the aging process in animals such as the minnowlike African killifish I’d watched fiercely guarding his territory.

The killifish is especially important to researchers like Brunet because it has an extremely variable, albeit short, life span. One strain from eastern Zimbabwe completes its entire life cycle — birth, maturity, reproduction and death — within about three to four months. Another strain can live up to nine months.

It’s also a vertebrate, meaning it belongs to the same branch of the evolutionary tree as humans. This gives it a backbone up over more squishy models of aging like fruit flies or roundworms — translucent, 1-millimeter-long earth dwellers you could probably find in your compost pile if you felt like digging.

I hope you’ll read the rest of my piece to learn more.

Previously: My funny Valentine – or, how a tiny fish will change the world of aging research, Stanford Medicine magazine reports on time’s intersection with health and Living loooooooonger: A conversation on longevity
Photo of Anne Brunet by Gregg Segal

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