Archive for May, 2009

Inside the Cancer Cell

May 28, 2009

The American Cancer Society says deaths from all cancers is dramatically declining.  Death rates are down 19% for men and 11% for women over the most recent 15 years for which data are available.  The biggest reasons are stopping smoking and earlier detection of colorectal and breast cancer.  Better diets and exercise likely also play a role.  So do much improved anti-cancer drugs.

During a visit to Joe Gray’s laboratory in Berkeley, California, managed by the Lawrence Berkeley National Laboratory, I saw young men and women scientists busily working on a fabulously intricate analysis of breast cancer tumors.

“Each tumor is unique, actually molecularly different from every other,” Gray explained.  He is a quick-smiling bear of a man who started his professional life as a nuclear physicist.  It was the death of his father from lung cancer that set him on the path to uncovering the mysteries of cancer cells.

“We now can peer deep into the inner workings of the cancer cell in exquisite detail.  We can then determine which drug therapies will work best and, in essence, create the ultimate in personalized medicine: the most effective anti-tumor molecule with the least effect on normal tissues.”  Gray walked me around his lab, gently insisting I wear protective eyewear.

Gray’s research includes discovering why some tumors become resistant to first-line drugs.  His latest work is on HER2-receptor positive breast cancer tumors.  This type represents about a quarter of all breast cancers, and usually is discovered much too far-advanced in younger women.  This is the type for which drugs such as herceptin and lopatinib were designed.  It is the aggressive kind of cancer that killed my good friend and colleague, Faith Fancher, several years ago.  Ironically, Faith’s stepson, Sean Drummond, accompanied me on this day, videotaping a news story.

Gray discovered that one of the reasons this particular cancer is so aggressive and difficult to treat is that the tumor cell makes thousands of extra copies of HER2 genes that help the cell survive.  There are about 30,000 genes in a cancer cell, he says, and maybe 15% of them go haywire, either over-expreessing or under-expressing and dysfuntional.  Then, the tumor often becomes resistant to the drugs, much like bacteria become resistant to anti-biotics.  Gray says he’s discovering the molecular trick that allows the tumors to become resistant.  He plans to publish a study shortly that may help researchers find a new way to kill the tumor cells.  That will be a big step toward better treatment for breast cancer.

Gray, in collaboration with colleagues at UC San Francisco, across the bay, has just won a several million dollar award from the Stand Up 2 Cancer Foundation, to pursue exactly this strategy.

Driven first by a family tragedy, now by his curious intellect, Joe Gray can see into the heart of a killer, and knows its weaknesses.  It’s knowledge that may save your life, or that of someone you care for.


Vaccine Choice and Risking Lives

May 26, 2009

Lifestyle and choices are key California concepts.  Parents who eat only organic vegetables, wear clothing from recycled hemp and refuse to vaccinate their children, are not hip.  They’re risking their kids’ lives and are putting at risk children around them, say pediatricians.

“Celebrities get media attention, and unfortunately some of them are saying ‘don’t vaccinate,'” says Rina Shah, the Walnut Creek, California, mother of 15 month old Dia.  Shah is a working mom, a pediatrician in private practice.  “This is a dangerous message for their children and mine, because pertussis (whooping cough) is still very much a problem.  We live in a diverse and well-traveled community and this disease is with us.”

In the 2007, the most recent year for which figures are available, more than 10,000 children nationwide had confirmed pertussis, and ten died.  The bacterial infection hospitalizes hundreds every year in ICU’s.  “I think I may have caught it myself,” Dr. Shah said, “I worked in a (San Francisco Bay Area) clinic where there were several cases.”  Immunity sometimes wears off even after vaccination.  For Shah, it was a couple of months of chronic coughing.

A new Kaiser Permanente study in the journal Pediatrics suggests that parents who decline routine DPT vaccines put their children at a 23 times greater risk for pertussis.  Refusal raised risk from about 1-in-500 to 1-in-20.  In the Kaiser study, 92% of children who got pertussis were not vaccinated.  A recent study in the New England Journal of Medicine revealed a similar risk for measles.  Vaccines have controlled or eliminated polio, smallpox, mumps, measles and rubella.

All U.S. states require childhood immunizations before children can attend school, but permit medical exemptions from school immunization requirements.  48 states allow religious exemptions, and 21 states allow exemptions based on philosophical or personal beliefs.  In California, parents need only “submit a letter or affidavit stating the immunization is contrary to his or her beliefs.”

“Bad public health policy,” says Dr. Randy Bergen, a Kaiser pediatrician and infectious disease specialist.  Bergen, who’s worked overseas in Liberia, India and Thailand, knows first-hand the risks of third-world medicine.  “Modern vaccines save lives, are safe and should not be refused by parents without medical counseling.  Refusals put children at serious risk.  I support strengthening the exemption law.”

“I’m a mother and I want to be able to make choices for my children,” says Shah.  “I completely support that concept.”  While we talked, little Dia squealed and giggled while chasing bubbles in the backyard.  Dia has had her immunizations. “But, before granting a vaccine exemption, schools should require parents get at least some minimum vaccine education.  Without knowledge, ‘personal belief’ has no value.”

A Different Yosemite

May 23, 2009

The spectacular big trees that so define Yosemite National Park in California’s central Sierra Nevada are dying faster than young trees can replace them.  About a quarter of the biggest trees have disappeared, compared to a detailed survey done in the 1930’s.  Researchers say global climate change is responsible.

Rapid recent changes in temperature appear to have caused an unexpected unbalancing of the web of life that sustained the forests for millennia.

“We expect more intense fires,” says UC Berkeley Forestry Specialist Bill Stewart, who studies the ecology of forests.  “Those fires will in turn kill more trees.  Dense stands of big trees in Yosemite and Sequoia National Forests will thin out,” he says explaining fewer young “recruits” have grown in the vacant spots.   “Expect to see a lot more sunlight in those forests.”

It’s just one snapshot of a much bigger problem: a Western US-wide die off of large diameter trees, reported earlier in Science.  Forest scientist John Byrne of the USDA Forest Service and colleagues discovered larger trees are dying twice as fast as just 25 years ago.  Climate change disproportionately favors insects and diseases, such as fungi, which can move with the wind.  Trees do not have that adaptation for rapid acclimatization.

Temperature is a key driver of ecological balance.  Pine bark beetles, for instance, are devastating western forests.  Normally, the beetle dies when temperatures under the bark cool to about 25F.  A few years ago, they began to live through winters when the low temperature rose just one degree warmer.  Now in many parts in the Rocky Mountains, temperatures drift above the kill temperature all winter long.

The key tree species in Yosemite that are dying off are white fire, lodgepole and Jeffrey pines.  So far researchers have not identified as hard hit the iconic Giant Sequoia and redwoods.  Those big trees appear hardier, but require abundant water to survive.  Drought is stalking the Sierra for a third straight year, and experts say there is significant risk as well to the signature specimens that survived two thousand years before the burning of fossil fuels.

Know the consequences of driving your SUV.

Tahoe Temblors and Seche

May 16, 2009

California’s stunning Lake Tahoe straddles three earthquake faults, in a 6,000 foot high section of the seismically active Sierra Nevada mountains.  Two studies from Scripps Institution suggest a magnitude 7 quake there is long overdue.

“A large earthquake could set off an underwater landslide,” said UC Davis physics and geology professor John Rundle, the Director of the California Institute for Hazard Research.  “A large landslide could trigger a seche, which is what we call a tsunami in a lake.  It could send a 30 to 40-foot high wall of water across Tahoe shoreline communities,” he said.  “Local officials are not taking this risk very seriously.”  Rundle is also advising the Undersea Voyager project which has a small submersible in Lake Tahoe, looking for bottom clues to previous earthquakes.

“We’re trying to find indicators of past quakes, to help us figure out how often they’ve happened,” said Bob Oberta, an engineer with the project.  The submarine is now transecting three faults that lie at the bottom of 1,645 feet of still-amazingly clear water.

What’s most troubling about the research is that sonar profiles of the lake sediment reveal a clear history of big quakes, averaging one every two to three thousand years.  The most recent large quake was 4100 to 4500 years ago, along the West Tahoe Fault, according to the sediment records.

“The next large quake could happen any time.  We put the probability of a magnitude 7 quake at Lake Tahoe at between 2 and 3 percent per year,” said Rundle as he showed me his research laboratory, a collection of earnest grad students and post docs at double-wide computer screens.  “That means it’s likely in the next forty years or so.  The probability changes daily,” he went on, because of other seismic events nearby relieving or increasing strain on the faults, or other factors including plate movement, which at Tahoe includes a steady shearing and pulling apart of about a millimeter per year.  “That’s why there’s such interest in quake forecasting.”

He showed me a lengthy computer plot of California earthquake “record-breakers,” quakes that happened when they weren’t expected.  “There may be trends in these data; quakes tend to follow trends, much like the stock market.”  Research associates are poring over data that include temperature and air pressure as well as readings from fault-creep strain meters.  “It seems we’re coming into a period of increased seismic activity in California, especially along the major faults in Central and Southern California,” Rundle said, “but we can’t just yet make the kind of forecasts that would be useful.”  He is, he says, working very hard on just that.

When visiting Lake Tahoe, keep a wary eye on that sparkling blue water.

New Eye In The Sky

May 15, 2009

Despite a stuck bolt and an hour longer spacewalking than planned, Atlantis astronauts successfully installed the half-ton piano-sized Wide Field and Planetary Camera 3 on the Hubble Space Telescope.  They also installed some other equipment.  For UC Berkeley astrophysicist and astronomy professor Alex Filippenko, a new scientific era is about to begin.

“I’ve been waiting two years,” said Filippenko in his corner office that sports a terrific view of Cal’s campanile.  He has a jar of pickles on his desk for “electrocution,” he says, a class demonstration on sodium absorption.  He sports a wide, boyish grin and remarkable enthusiasm for an astonishingly complicated problem in modern physics, what’s called “dark energy.”

“This is one of the most fundamental questions in all of science right now.  What is the physical nature of the dark energy?”  Filippenko patiently explained a tug-of-war that now shapes our universe.  It involves stuff no one really knows much about: dark matter and dark energy.

“Only about four percent of the mass in the universe is what we can see.  The rest we can’t see, and really haven’t yet identified,” Filippenko said carefully.  In the first five billion years or so after the Big Bang, dark matter (some kind of gravity-inducing stuff) as well as regular matter seemed to rule:  the universe spread out in a slightly slowing expansion.  It looked like what you’d expect from the normal laws of physics, in the grip of gravity as we know it.  But after about five billion years, something else seemed to take control, and without any other way to describe it, astrophysicists called it “dark energy.”  It seems to defy all logic.  It’s pushing galaxies farther apart, faster and faster.

To get a handle on the unexplained expansion, Filippenko says you need some way to measure distance reliably.  Relatively close by, where stars are easier to see, Cepheid variable stars serve as mileposts:  they have a known instrisic brightness, and so like a headlight on a car, you can tell how far away they are.  Filippenko showed me a Hubble photo of the stunning M101 spiral galaxy.  It is about 25 million light years distant, and Cepheids allow that to be measured with remarkable accuracy.  But Cepheids are too faint be seen from several billion light years away, so Filippenko and others use supernovae: exploding stars of a certain type, that also have a determinable brightness.  Even though they release an astonishing amount of energy, they are so faint at these distances, ordinary telescopes cannot see them.

That’s where the Hubble Space Telescope comes in.  To see and analyze these “mile markers” you need a powerful camera, above the ultraviolet-blocking atmosphere.  The new WFPC3 is more than 35 times more sensitive in ultraviolet than its predecessor.

“We’ll be albe to see these stars exploding within 650 million years of the Big Bang,” says Filippenko, “revealing the rate of expansion of the early universe, and hopefully allowing us to figure out what this mysterious dark energy really is.”

Filippenko was part of a team that recently published the most accurate estimate yet of the cosmic expansion (74 kilometers per second per megaparsec) but says new instruments on Hubble will greatly increase what are called “constraints” on the value, known as the “Hubble Constant” making experimental verification much more revealing.

Why is any of this important to anyone outside of the astrophysics community?  “We are all star stuff,” said Filippenko with a nod to Carl Sagan, “and knowing about the history and future of the cosmos helps us understand our place in the universe.”

Thanks to the Shuttle Atlantis astronauts we may put a smaller pin in the map.

Grab and Go

May 14, 2009

In the end, it seemed so easy. Astronaut Megan McArthur controlled the manipulator arm aboard Shuttle Atlantis, and snagged the Hubble Space Telescope as the two spacecraft sped along 350 miles over Australia.

This sets the stage for five spacewalks over five days, to repair and update the 17 year old Space Telescope.  It now may continue working for at least five, perhaps eight more years.

“I’m excited,” said NASA Astrophysicist Robert Rubin in his research-paper cluttered office at Ames Research Center in Mountain View, California.  “Assusming it gets fixed, we have another chance.”  A chance at solving a fundamental mystery about the origin of elements in the universe, that he says was cut short when the STIS (Space Telescope Imaging Spectrometer) aboard Hubble failed four years ago.

Rubin has been researching the M1-42 Nebula, an unusual planetary nebula 25,000 light years from Earth, in the constellation Saggitarius.  M1-42 is often called the “Bird’s Nest” nebula because of its oval shape.  It looks rather more like a lizard’s eye.

Rubin says this cluster of stars holds a key clue to a discrepancy about the abundance of elements found in the cosmos.  He’s been using Hubble images exclusively, especially ultraviolet images that could not be made by earth-based telescopes.   Those wavelengths penetrate the atmosphere poorly.

With a new Wide Field Camera, and a repaired STIS, Rubin says his team may finally discover the dense, relatively cool and hydrogen-deficient clumps of matter that, he says, will help confirm current theories.  He’s been unable to find them so far.  Without these clumps, astrophysicists may have to re-write the textbooks on how everything we see got here.

C’mon Astronauts, we’re rooting for you!  Re-writing the history of the Universe could get very messy.

Fingers Crossed

May 13, 2009

Shuttle Atlantis astronauts discovered some ‘dings’ to heat shield ceramic tiles on the right wing chine (near the fuselage) of the orbiter. NASA says the damage appears ‘minor’ and likely occurred 103 seconds after launch, when impact sensors registered an anomaly.

Engineers will go over detailed images from the robotic arm camera and telemetry from the external fuel tank camera before making a decision on the flight.

It was left wing Reinforced Carbon Carbon damage that brought down shuttle Columbia six years ago, killing all seven astronauts.  For now the Atlantis mission continues as scheduled.

“I’ve got my fingers crossed,” said UC Berkeley research astrophysicist Barry Welsh, who is an investigator with the the Cosmic Origins Spectrograph program. The COS camera is aboard Atlantis, heading for installation on the Hubble Space Telescope.

The camera was built partly at UC Berkeley Space Sciences Laboratory, where I had an opportunity to see an earlier version of the device in the lab’s clean room.

About the size of an astronomy textbook, the camera is a super-sensitive detector of ultraviolet photons.  It will be aimed at distant quasars, and their light will pass through the so called ‘cosmic web’ of matter scattered through the universe.

“Analyzing the spectra of that light, we can determine, mass, composition and other characteristics,” says Welsh, and that can help his team map the distribution of matter in the universe.

Welsh is an animated, quickly smiling 56-year old Brit, who wears shorts, running shoes and a Cal rugby shirt as he darts around the lab.

“Why is it laid out this way? Is it the gravitational effect of dark matter or dark energy or something else? No one knows.”

Welsh gained some fame a few years ago using similar technology to discover that our solar system lies near the center of a ‘gas free bubble’ in the Milky Way.  Something blew the ordinary cosmic dust and gas away about 5 million years ago, making a sort-of chimney through the disk of stars in which we reside.

“I’d really like to get a great discovery before I retire,” he said gesturing at the COS.  “It’d be wonderful if they named it the ‘Welsh Chimney’ or something,” he laughed.

It’s more than mock ego that drives him; he said he’s been fascinated by the stars since he was a child.  Now Barry Welsh’s camera may reveal the very fabric of space, and shine a light on the deepest of mysteries: What is the Universe all about?

It Grows Green and It Grows People

May 7, 2009

I met 82 year old Jean Leukin today.  She lives in a different world.

She is very animated and engaging, big blue eyes framed by outsized spectacles.  She smiles easily and moves like an agile athlete many years younger.

She asked me not to tell you her exact medical diagnosis.  “That’ll mean I’m dead,” she frowned.  I promptly said it would stay between us.   Although I’m certain she has completely forgotten about it, I’m going to keep my word.   I’ll say Jean has a memory issue, some increasing difficulty recalling and learning new information.

She’s part of a new program shepherded by UC Berkeley, called PhotoVoice.  PV has been around for quite a while, useful in Huntington’s patients for example, but this study is less about the patients than their caregivers.

Jean lives in an assisted-living facility in Oakland, California, called Age Song, a delightful “wander-guarded” residence near Lake Merritt.   It is for elder people like Jean, who have some remembering trouble.  In a terrace garden on the second floor, surrounded by trees, Jean and I could hear chickens crowing across the street, punctuating the busy hum of people heading to lunch.

Jean had a camera in her hand, carefully putting it up to her eye, sometimes crouching her still-lithe former dancer’s body to get the “just right” angle.  The camera fit in her fingers like the hand of an old friend.  She seemed to have a purpose and was completely engaged in the artform.  After a few minutes photographing a Japanese maple, a lovely blooming wisteria and a well-attended bird feeder, Jean sat down on a planter next to her therapist, Nader Shabahanagi.

Nader is thin and intense, a humanities and philosophy PhD who sprinkles his conversation with references to Buddhism, Goethe and the Scottish psychiatrist R.D. Laing.  He is passionate about his work on this ‘new paradigm’ as he calls it, about re-assessing people with progressive forgetfulness.  He avoids words such as “Alzheimer’s” and “dementia.”

“It grows green and it grows people,” says Jean about the maple tree.  Nader chuckles and parrots what seem to be nonsense words, in a way that makes me wonder if he doesn’t recognize some inherent and deeper truth in them.  He and Jean sit and touch hands and smile at the people-tree.  After a few moments, she turns to him and says, “it wasn’t here a couple of hours ago.”  He nods and they both look back at the clearly well-established tree.

“It’s not about remembering, as much as it is about an ability to engage,” Nader explains later.  He has worked with Jean for several weeks now, discovering her latent talent for photography (she says she took a lot of pictures when she lived in New York, on Long Island) and more importantly, discovering what it is she finds interesting: the shape of the maple leaves, the colors of the flowers and the curve of the bench that may remind her of sitting with her policeman father on summer afternoons at the park.  Nader says he wants to know how she feels and “what grabs her, excites her and gives her meaning,” especially, he says, “living in an assisted living facility ” without the mental clarity and word command this former teacher certainly once had.

Nader reviews her digital photos on his computer.  They are well-composed, balanced and maybe better than the average amateur’s, but what Nader is looking for is the theme and thread of Jean’s attention.  He discusses the photos with her and mentions the colors and shapes;  her eyes brighten, her voice strengthens and she sits taller doubtless feeling as if someone else, FINALLY someone else understands.  It’s clear she hears and embraces, if not the specific words, the tone and quality of his voice, his gestures and his openness and acceptance of her.

“They’re teaching us,” Nader says, “teaching us how to communicate in a different way, how to be sensitive again to things we have lost sensitivity to.”

“Elders have a tremendous amount of things to teach us.”

The point of the PhotoVoice program is to learn methods to help caregivers, staff and therapists develop a new perspective on these forgetful elders, these weary and wise and often misunderstood people who may simply be in a different reality from us.  Their world is challenging precisely because WE are in a different reality.

As I leave, Nader grips my hand and says “I hope when you and I need this kind of care, our caregivers will have learned some of those things.”

I hope that too.

H1N1 “Mild”

May 6, 2009

Federal health officials today said the A/H1N1 influenza is milder than first thought, and schoolchildren should go back to classrooms that were cleared after suspected cases were identified.

Great news for the families of 400 students at Malcolm X Elementary in Berkeley, California. District officials sent the children home Monday after a parent and two students had suspected H1N1 infections.

“It’s caused a hardship for childcare, so that’s a relief,” says Principal Cheryl Chann. She recorded a phone-tree automated message telling students and staff to return in the morning.  The bell rings at 8:10am.

This improving flu news did not come soon enough for San Francisco housekeeper Celia Ramirez. Over the weekend she says her son and daughter both spiked fevers. Worried at the specter of a “killer virus” she took them to a hospital emergency room. She says the doctor told here it was “no problem it’s OK” they had ordinary flu, she got the bill: $606.25.
There’s another story there.

Dr. John Swartzberg, an infectious disease specialist with UC Berkeley’s School of Public Health, says even though the news is good from federal officials, it is not the time to ignore this emerging virus.
“We have to be aware, we have to be cautious, we have to anticipate the worst and plan for that,” Dr. Swartzberg told me as he showed me a 1918 flu pandemic graphic he presented at hospital Grand Rounds earlier in the day.

This graphic told the story. A bump in flu around early June, then a flattening to almost zero for the next six months. In September, the graph shot up many times higher, dipped again in Summer of 1919, and then shot up a third time in Fall 1919.  (Check out my previous “Flu Factories” entry.)

Dr. Swartzberg points out that no one can predict what this virus will do, how it will mutate, how infectious or lethal it may become.

Why Influenza Fizzles

May 4, 2009

New analysis of the H1N1 influenza from Mexico reveals it is only barely able to keep itself reproducing in the human population.
RNA viruses mutate at a fairly predictable rate and this can provide a reliable yardstick of age. Based on new data from very small mutations detected so far, British scientists say the A/H1N1 from Mexico first evolved no earlier than September 2008, and possibly as late as January 2009.
From this, they calculated a key “reproductive” or “transmissibility” rate, known as R(0).  Less than 1 and the virus declines in the population. They say the A/H1N1 strain today has an R(0) of 1.16.  By comparison, seasonal flu may have an R(0) of 1.5 to as high as 3.  But influenza is highly variable , and typically the R value of a novel virus increases with each generation as the it adapts to its human host.
US researchers at Los Alamos National Laboratory have calculated that in 1918, the “herald wave” or first outbreak of the pandemic had an R(0) of 1.45, slightly more infectious than today’s.  But in the Fall of 1918, that virus (also an H1N1) came back with an R(0) of 3.75 to 4.5, and began a devastating sweep across the globe, killing about 40 million previously healthy adults.
The Fall 1918 virus did have three specific genes allowing it to reproduce deep in lung tissues; exactly when it mutated to that form is unknown. Today’s A/H1N1 lacks those killer genes so far, but virologists say new mutations can pop up at any time, and health officials have to keep a wary eye on this new virus, as well as the H3N2 subtype that’s circulating in the US and abroad.
It’s a dangerous world out there, wash your hands.