As I discovered while editing the new Stanford Medicine magazine report on childbirth, the placenta is a terribly important organ yet a big question mark for most people. To help demystify it we used a new kind of storytelling - an interactive simulation that allows you to observe and control the development of the placenta. It’s a companion to an article on the epidemic of the potentially fatal condition known as placenta accreta.
The producer, David Sarno, a former Los Angeles Times technology reporter and a 2013 John S. Knight Journalism fellow, built the simulation using the tools of video game design. It’s the first finished product of his start-up, Lighthaus, dedicated to creating interactive digital stories. If you’re curious about the placenta - or this new mixture of technology and storytelling - click on the image above to get to the video. (Note: To run the program you’ll need the Unity web player, which is free and downloads pretty quickly at the link.)
PubMed, the massive index of biomedical research articles, has begun an experiment: Enabling the posting of comments on the articles’ citations. This might not seem like a big deal, but in this case the comments system, PubMed Commons, is creating a buzz.
Some of the tweets following the Oct. 22 announcement: “PubMed Commons will change the way science works, but I predict a big impact on science bloggers as well” (@Neuro_Skeptic), “Science buzz and criticism gets a powerful boost” (@phylogenomics) and “Seriously get ready for a turbo-charged #PubMed (@AlbertErives).”
It was actually two Stanford professors - biostatistician Rob Tibshirani, PhD, and biochemist Pat Brown, PhD – who got the project rolling. I talked with Tibshirani for an article in Inside Stanford Medicine about the project’s beginnings and what he hopes it will accomplish. For starters, he sees it as a way for readers to note errors in the scientific literature in a place other researchers will see. But he also hopes it will generally expand scientific discourse and build community:
“Science can be lonely,” Tibshirani said. “Just having people talk about your work is nice. Sure it’s nice to have good comments. But it’s nice to have comments at all. At least someone cares enough to read your paper.”
For now, during this expanded pilot phase, only individuals who have published articles indexed in PubMed can make comments or see them. Tibshirani says he’s hopeful the leaders of the National Institutes of Health will decide to allow the general public to see the comments too. More on the how and why of the project as well as the quandary over anonymous comments (yea or nay) in the article.
Think of what you see in this video as a message going viral, only it’s spreading not in cyberspace but in cytoplasm. The video shows a trigger wave, an under-appreciated chemical phenomenon that can help cells get things done fast. Stanford graduate student Jeremy Chang and professor of chemical and systems biology Jim Ferrell, MD, PhD, published a video of this scene as part of their recent paper (subscription required) in Nature. The August 29 paper describes several lines of evidence all pointing to the conclusion that in frog eggs the dramatic dance of mitosis – in other words, the process of the egg dividing and forming two new eggs – is launched by trigger waves.
At the end of this post I’ll explain in more detail what’s happening in the video. But first I’ll answer the question: Why study how frog eggs divide? It’s not as odd as it sounds.
The eggs of these frogs (African clawed frogs or Xenopus laevis) are popular cells to study because, as cells go, they’re huge – about 1 millimeter in diameter – which makes them relatively easy to manipulate and observe. But of particular relevance for this study is a mystery Ferrell and Chang wanted to solve concerning mitosis. Mitosis in a frog egg happens way too fast than would be possible if it were orchestrated merely by proteins randomly diffusing hither and thither – which is how most people assume things work most of the time in cells. If only random diffusion were in play, mitosis in a big cell like this would take several hours, Ferrell said. But in reality it takes just 10 minutes. So something more is going on and that something, as Ferrell and Chang have shown, is the cell’s equivalent of going viral: trigger waves.
“It’s a physical process that takes place in lots of settings,” Ferrell told me. “The spread of a fire in a forest is an example of a trigger wave. The spread of an action potential from the body of a nerve to its axon is an example. Or a joke spreading through YouTube. The main ingredient you need for a trigger wave is positive feedback. It’s an autocatalytic process.”
To learn more about mitosis in the frog egg, Chang and Ferrell looked at the master regulator of mitosis, a protein called cyclin-dependent kinase 1, or CDK1. Activated molecules of CDK1 not only start mitosis, they turn inactive CDK1 molecules into active ones. In other words, there’s positive feedback, and the result is a trigger wave spreading CDK1 activity across the cell.
To scale up the trigger wave to make it easier to see, Chang whipped up an extract from the guts of many frog eggs mixed together. He also figured out how to get the nuclei in the extract to undergo mitosis over and over again – in this video, seven rounds, and sometimes up to 15. (Ferrell said Chang is legendary in Xenopus research circles for engineering such a massive multiplicity of mitoses. Chang said it was sheer luck: Switching from a glass tube to Teflon to hold the extract did the trick.)
The flashing green spots in the video are the nuclei undergoing mitosis: They disappear when the cell pulls itself apart and reappear when the division is complete. You can see trigger waves traveling from both the top and the bottom of the tube. Take a look at the topmost nucleus and you’ll see it blink off, shortly followed by its neighbor and so on down the line. The same happens if you follow the nuclei from the bottom up. The first cycle is a little messy but later rounds are clearer.
Karlene Cimprich, PhD, is a Stanford professor who normally studies how cells keep their strands of DNA in proper working order. Her newly published research (subscription required) provides insights into the DNA repair process, but as a very interesting bonus it also turns up a new avenue for drugs to treat kidney disease. The unifying factor for these disparate discoveries is the mysterious antenna-like cellular structure called the primary cilium.
Most people don’t realize that nearly every cell in the human body has an antenna. Well it does, even though the rod-like projection was overlooked for decades after its discovery more than 100 years ago. An article I wrote in Stanford Medicine magazine explains:
The primary cilium is not a recent discovery. Swiss anatomist K.W. Zimmermann described the structure and suggested a sensory role in 1898, but other scientists largely ignored it. In later years it was written off as a quirk of evolution. The outburst of research over the past decade has revealed that the tiny projection is acting as the receiving station for cells’ signaling chains, the communication networks that govern and coordinate cell actions.
In the past two decades scientists have started paying attention to the primary cilium, and they’ve discovered not only its receiving-station role, but its importance for health.
Cimprich’s research started out having nothing to do with the primary cilium. About five years ago, Renee Paulsen, then a graduate student in her lab, launched a search for proteins needed to repair damage to a cell’s DNA. Another graduate student, Claudia Choi, assessed some of those proteins that were especially needed to repair DNA when the cells were stressed.
A literature search revealed intriguing info about NEK8: It’s also faulty in certain kidney diseases — which are known to result in part from defective primary cilia.
This led Cimprich and her team to the work reported today in Molecular Cell: details of the molecular mechanism NEK8 uses to prevent DNA damage and clues to how NEK8’s malfunction relates to the primary cilium and kidney disease.
“Preparation is everything,” said Stanford’s chief of trauma and critical care surgery, David Spain, MD, when I asked him about the breathtaking response by the Stanford and Lucile Packard Children’s hospital staff who helped care for the influx of Asiana Airlines crash victims July 6.
In the past year, they’ve participated in two large-scale mass-casualty exercises: One, an active-shooter scenario, was a statewide effort; the other, an earthquake scenario, was a joint training with Stanford University, Stanford University School of Medicine, Santa Clara County and Palo Alto.
Maybe most fortuitously, just last month as part of a Stanford Office of Emergency Management training program, every emergency department nurse completed training for triaging disaster casualties, and then on June 14, just three weeks before the crash, emergency management program managers Eric Giardini and Laura Harwood ran a simulation with the whole emergency department of “code triage” — exactly the scenario faced after the plane crash.
When I talked about that simulation with Brandon Bond, the administrative director of the emergency management office, he told me how valuable it proved to be: “They set up the patient triage system in the ambulance bay, deployed the triage disaster supplies as well as simulated patient triage. Every component that the team had exercised last month was utilized during the event July 6.”
It’s right before our eyes: The water we drink, the air we breathe, our neighborhood — in other words, our environment — can make or break our health. This simple truth gnawed at Pulitzer Prize-winning investigative reporter/Stanford medical alum Sheri Fink, MD, PhD, as Hurricane Sandy approached New York City last fall.
The images of the hurricane spinning toward my city, and the knowledge that thousands of New York’s most fragile residents would be left in its path, in facilities that were not hardened to withstand significant flooding or power outages, made my stomach sink.
Fink’s article on heroics in New York City’s hospitals and nursing homes during Hurricane Sandy is part of the special report, “Environmental impact: The health effect,” in this summer’s issue of the magazine, which has just been published.
Also in the issue:
“Water solutions:” Actor Matt Damon and engineer Gary White, co-founders of water.org, discuss how they intend to solve the global water crisis.
“Priming the pumps:” The tale of a trip to the slums of Dhaka that led to a radical solution for contaminated drinking water.
“Street smarts:” A feature on senior citizens using tablet computers developed at Stanford to wake up city officials to safety hazards in their working-class neighborhood.
“Close encounters:” A story on scientists who are combining data from satellite images and studies on the ground to grasp the ecology of disease-bearing pests.
This issue’s “Plus” section, featuring stories unrelated to the special report, includes:
“Leo and Frida:” The tale of the friendship between artist Frida Kahlo and Stanford surgeon Leo Eloesser, MD.
“Winnie’s tale:” The story of how a cancer treatment 30 years in the making came in the nick of time for centenarian Winnie Bazurto.
Over two long weeks in January, sculptor Alyson Shotz and team installed Three Fold, her new sculpture in Stanford Medicine’s Li Ka Shing Center for Knowledge and Learning. She got the job done with a team of art installation specialists from Atthowe Fine Art Services and DCM Fabrication. Together they assembled the sculpture’s three sections, covered the metal slats making up each section with thousands of acrylic pieces (with the help of more than 20,000 screws), peeled the blue protective film off the acrylic, mounted the sections on cables and raised them up.
This video shows those weeks compressed into less than five minutes.
The end result? As I wrote in Inside Stanford Medicine last week:
Sailing above the Yang and Yamazaki Lobby on the second floor of the center, the glimmering, undulating lattice appears lightweight and ephemeral — like a scaffold made of dragonfly wings. In reality, it weighs more than 3,000 pounds. The 56-foot-long sculpture, titled Three Fold, is actually made of curved aluminum slats covered on both sides with dichroic-acrylic-coated plastic. Though the acrylic is clear, it both reflects and refracts, resulting in a spectrum of iridescent colors that change with the angle and quality of the ambient light.
Even if I didn’t know anything about what went into creating Three Fold, Stanford Medicine’s new sculpture by Alyson Shotz, I’d love it. As I wrote in today’s Inside Stanford Medicine, the 56-foot-long sculpture, which hangs from a ceiling in the Li Ka Shing Center for Learning and Knowledge, shimmers in an ever-changing array of iridescent colors. Pretty colors get me every time.
There’s a lot more to the sculpture than pretty, though. Shotz is a widely respected artist. Her works, exhibited in prestigious museums like New York City’s Guggenheim and DC’s Hirshhorn, are engineering feats inspired by scientific concepts - this one, by a CAT scan. As Shotz tells it:
I was very interested to learn that CAT scans image by sections, using a penetrating wave. This seems quite relevant, as my work represents an imaging of space, and the wave illuminating the shape, in this case, is color: the varying wavelengths of light that the viewer will see reflecting off the sculpture.
Shotz has other interesting things to say in a Stanford video, above, where she describes how her creative process reminds her of protein folding:
Proteins achieve functionality when they go from a non-dimensional shape to a folded three-dimensional shape, which is fascinating to me because when I started these drawings the lines are actually non-dimensional and then I expand them out into three-dimensional surfaces which then become functional as sculpture.
While reporting the article I learned that the artwork was born on a computer. I found out that despite its gossamer appearance, it weighs more than 3,000 pounds. (It’s made of about 10,000 pieces of custom-cut plastic, 600 pieces of aluminum and more than 20,000 screws.) And I learned the secret behind the pretty colors: dichroic-acrylic-coated plastic, which not only reflects light but refracts it.
Three Fold is being dedicated this week to the medical school’s former dean Philip Pizzo, MD. If you’re in the neighborhood, it’s worth a look.
I felt a little guilty about pushing my colleague John Sanford to confront his blood phobia as part of a story he was writing for Stanford Medicine magazine. I feel fine about it now, though. While writing it, John overcame the phobia! And the story turned out very well too. In fact, it was recently singled out by long-form journalism curator Longreads as a story worth reading.
Here’s how it starts:
I awoke close to midnight. It was the middle of August, in 1992, and the windows were open in the room of the Paris hostel where I was staying. The air was warm and still. My chest felt moist with — sweat? I touched the substance with an index finger and pressed it to my thumb. It felt tacky. Blood!
(That’s John in the photo, by the way. Yes, he’s holding a test tube of blood.)
Goethe didn’t know the half of it when he penned this line for the character of Mephistopheles, in “Faust,” more than 200 years ago.
In those days people believed blood held mystical qualities and was a potent life force. No wonder Mephisto wants the contract for Faust’s soul signed in the stuff.
But what exactly does blood do?
The new issue of Stanford Medicine magazine tells blood’s story, from 17th-century attempts at blood transfusion to the workings of a modern blood bank to today’s studies of gene therapy to treat hemophilia.
Inside the issue:
“Blood quest:” An article on Stanford’s early fight to prevent the spread of AIDS by screening blood – while other blood banks argued against testing.