“I got into the clinical trial… I was lucky”. A story about luck, drugs, and cancer treatments.

I had tears in my eyes searching through my emails from three years ago. One of my close friends (and brother of my cartoonist bff) had emailed my sister asking for medical advice. What my friend Junior was after, was a second opinion for his father. He said “our family is in panic since we heard the diagnosis… At home, we are all terribly anguished”, to which my sister replied, “call anytime and we’ll try to help – after all, you are part of the family.”

Junior’s father had been diagnosed with follicular lymphoma, the most common form of non-Hodgkin lymphomas, and they were after a treatment. This was Brazil, where not all drugs are readily available. That’s where my sister comes in: she is a doctor and searched around for hematologist colleagues and experimental treatments. My friend however, is the one who did all the legwork. After several doctors and opinions, he got his father Beco the treatment he needed.

Fast-forward to three years later, where Beco and I reminisce and he tells me more about the ordeal. He describes the initial warning signs of  the disease: “fever, night sweats, and rashes… I discovered my diagnostics by chance, during a tomography exam to find kidney stones.”

The recommended chemotherapy treatment for non-Hogdkin lymphoma (a form of cancer where B-cells are overactive) is a drug cocktail called CHOP. Each letter in the acronym represents a different drug, which are combined with the goal to attack cancer from multiple fronts (e.g., one drugs blocks DNA while another prevents B-cells from multiplying).

Rituximab is a new drug (an antibody that binds B-cell membrane proteins), which can be coupled with the CHOP regimen. Beco tells me on an email that “the difference of coupling rituximab with CHOP is that it gives the patient three extra years in remission.”

The drug targets CD20 proteins on the membrane of B-cells. We don’t know for sure what function those CD20 protein is performing, but it is believed that it acts as a gate for the passage of calcium ions into B-cells. Researchers have looked into that binding mechanism, in which rituximab binds to its target specifically on amino acids 170-173 and 182-185. To get a snapshot of the drug in action, Du et al. obtained an X-ray image of the crystallized rituximab bound with a piece of CD20. The researchers grabbed a small chunk of the CD20 protein corresponding to amino acids 163 to 187 (represented as the tiny string on the image below).

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A panel: Rituximab is represented in yellow and green ribbons. The blue string represents the peptide extracted from CD20. /15073.long B panel shows electron representations, and C panel, a close-up. Image credit: Du et al,

Beco got access to rituximab combined with CHOP, or R-CHOP. He was even able to get a newer generation of drugs, bendamustine. But that’s because my Junior and his family found and signed him in to a clinical trial managed by an American laboratory. “I got into the clinical trial to use rituximab combined with bendamustine, which is a more efficient chemotherapy drug with lighter side effects. The latter is not even available in Brazil – I was lucky!”

Because of his treatment, Beco tells “Since my son found the clinical trial I participated in, the lymphoma is under control. I’m still being treated with rituximab every two months for another year.” And a similar outcome is what we would like to see for other Brazilian patients.

Rituximab is available in Brazil, but not listed under the universal healthcare system. That means that lymphoma patients are treated with CHOP, but not R-CHOP, which increases their lifespan. “It is not a matter of cost, because those patients and the system will spend more money in extra chemotherapy drugs, and will die earlier.”

A Brazilian non-profit organization, Abrale, used a petition to collect signatures of rituximab supporters. The Brazilian ministry of health asked for at least 50.000 signatures to consider adding the drug to the universal health care system. As of the past few weeks, the petition gathered 61.000 signatures.

Beco is now in remission for the past three years. “We hope it stays quiet for a little longer”. And now, it may as well stay quiet for many more Brazilian patients.

Book Review – One Well and Tree of Life

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The water you drank today may have rained down the Amazon rain forest five years ago… A hundred thousand years ago, it may have been frozen solid in a glacier. And a hundred million years ago, it may have quenched the thirst of a dinosaur.”

The inevitable cycle of water in our planet was described above by Rochelle Strauss, in her book One Well: the Story of Water on Earth.

Rochelle is a museum designer and science aficionado. One of her main interests is bringing a message of conservation to children. She recently sent me her two books, One Well and Tree of Life: the Incredible Biodiversity of Life on Earth. The books are beautifully illustrated (by Rosemary Woods and Margot Thompson, respectively), and their clear and concise language reflect their target audience. Rochelle writes for kids of 8-14 years old, but her books can resonate with any of us.

Both books have an underlying theme: how everything is interconnected. In Tree of Life, the author emphasizes how all organisms (plants, lichens, plankton, mammals, and insects) are part of the same web. In One Well, she explains how water cycles through our planet, and highlights our fresh water consumption.

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Tree of life offers a great notion of diversity of life. The pages show increasing number of species, leading toward complexity. At the same time, the author never loses track  of the species relationship in the tree (almost like the “you are here” type maps). I can see Rochelle capturing a child’s attention by telling us of biggest or smallest species inside a tree “branch”. She tells us that “the largest butterfly to flutter by is the Queen Alexandra’s birdwing butterfly. Found in New Guinea, …it is bigger than a dinner plate.”

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In my work I write a lot of content for young audiences, specifically to high schoolers. It can be tricky to communicate science to such a young crowd. One of our solutions is to use concrete, vivid examples that describe science research. Rochelle Strauss does just that over her pages. She uses examples that reach young minds and impress older ones too. Rochelle tells us that a birch tree “drinks” 300 liters, or two bathtubs, of water. Or that there’s more water in earth’s soil and atmosphere than in all rivers combined. In an email, she wrote me that “as for the water usage facts – I know they are quite incredible aren’t they? I actually had so much fun researching and then finding equivalencies to help kids grasp the magnitude of some of the numbers.” I had a lot of fun reading them too.

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The books also carry a powerful message of conservation. That dinner plate butterfly above is endangered due to habitat destruction. We use a lot of potable water for mundane activities (e.g., “it took 130 liters of water to make your bike”) in comparison to other countries without as much water for their disposal. One of the most alarming facts depicted in the story is that North Americans use 55 buckets of water per day, while Indian use seven, and Ethiopians, one.

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Rochelle offers solutions (there is a “notes to parents, guardians, and teachers” section on how to help), but above all, she offers a stimulating account of our natural world.

In my favorite excerpt, we learn that “the average white cloud weigh about twice as much as a blue whale”. A blue whale is a good indicator of scale. That kind of analogy not only makes the topic more approachable, but memorable. “The water you brushed your teeth today may have been the spray of a beluga whale 10 years ago.” I believe these vivid images, more than facts, are what sparks a child’s interest in science.

Find Rochelle Strauss on twitter (@rochellestrauss), on her website, or on Amazon.

New post on PLOS Sci-Ed: Space Education

I have a new post for PLOS’ Science Education blog:

“Life Support Team! We only have 3 minutes of oxygen remaining on the Space Station!”, shouts Commander Libby. Wearing a blue flight suit with middle schoolers clinging to her arm, Libby Norcross is a space enthusiast and teacher at the Challenger Center. She takes groups through the space simulators at the center, while (why not) coming up with some emergencies like the one above.

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Libby Norcross, educator at the Challenger Center. Photo by nasafans tumblr.

Learning from immersive scenarios

The Challenger Center is a learning institution geared towards STEM (science, technology, engineering and math) and offers immersive experiences to children. According to the center, they are an “…educational space simulator and STEM resource center that positively impacts students, businesses, and our community by fostering real-world skills—teamwork, communication, problem solving—in a totally immersive learning environment.”

Continue reading after the jump…

De-extinction: the wooly mammoth is the biophysicist’s cancer

On my first day teaching bioinformatics, I brought Michael Crichton’s book Jurassic Park to class. I showed the students a DNA sequence from the book  – a long string of A, T, C, and G that was supposed to form part of one dinosaur gene. As a class exercise, I asked students to convert that string into a protein sequence (it seems more bioinformatics teachers had the same idea).

The students were instantly intrigued. I attribute that class’ success to Jurassic Park. Both book and movie are embedded in our collective imagination. Who isn’t enthralled by the possibility of engineering dinosaur DNA and bringing the lumbering giants back to life?

Can we bring back the Tasmanian tiger? Photo by the author.

Can we bring back the Tasmanian tiger? Mike Archer at TEDx. Photo by the author.

I was able to attend the TEDx DeExtinction event in DC, thanks to an awesome boss and crew, who came along. There, molecular biologists and conservationists discussed the possibility of resurrecting extinct animals, while fans vouched for their favorite species (hello, dire wolf). The lecturers presented the technology, while ethicists and ecologists watched in horror.

The passenger pigeon is another candidate for de-extinction. Photo by the author.

The passenger pigeon is another candidate for de-extinction. Ben Novak at TEDx. Photo by the author.

There was talk of bringing back the wooly mammoth, passenger pigeon, bucardo, Tasmanian tiger and others. But like speaker and “molecular paleontologist” Beth Shapiro points out, we are still very far from step one. No surprise here. I went to this event not expecting to see a herd of mammoths any time soon. I went there to marvel at technology  and its applications. Or, like my colleague described it, “the moon race for biologists”.

Beth Shapiro is cautiously optimistic. Photo by the author.

Beth Shapiro is cautiously optimistic. Photo by the author.

Conservation efforts can benefit from de-extinction technologies. Lack of genetic diversity among captive breed populations is a serious problem. Breeding programs and SSPs (species survival plan) keep a studbook: a record of the genetic make up of all individuals of that species. Pairings are carefully calculated in order to increase genetic diversity. TEDx host Stewart Brand (check out his Reddit AMA) believes de-extinction can help with that: “de-extinction technology… can be applied immediately to help diagnose and treat genetic issues with endangered populations of living species. Viable cryopreserved DNA … can be used to reintroduce genetic variability in ‘genetic bottleneck’ situations for animals now rare and facing inbreeding problems.” And that’s not all. Cloning or iPCS (induced pluripotent stem cells) are technologies with immense potential, with applications that range from tissue engineering to livestock breeding, and perhaps even to support reproduction.

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Stewart Brand at TEDx. Photo by the author.

Funding dictates what research projects will go on and which ones will die.  And that is why I’m ok if a woolly mammoth or Jurassic Park-based creature functions as research ambassadors. Scientists depend heavily on policymakers and public support to guarantee funds for their work. It is increasingly difficult to obtain funds for basic research or anything that doesn’t have the word “cancer” or “heart disease” attached to it. Throughout my PhD I happened to work with both most of the time (design of protein inhibitors for breast cancer, and angiogenesis molecules for cardiovascular disease). I mean most of the time: when an application is not so direct or obvious (e.g., of studying the folding of a protein) we always highlight its future, potential, exciting, indirect and perhaps one day possible outcome (e.g., better understand Alzheimer’s). The woolly mammoth is the biophysicist’s cancer, and the passenger pigeon is his heart disease. I believe de-extinctioners were trying this PR approach.

Biotechnology for de-extinction. Photo by the author.

George Church explains the biotechnology behind de-extinction. Photo by the author.

But did it backfire? I saw many ecologists and ethicists disapproving of the entire thing. Are they spreading the fear? Is fear of science creeping out and reaching our scientific and (scientific-supporting) community? As Brand pointed out in his AMA, “fear has been institutionalized, not only by government but by (…) environmental groups broadcasting irrational fear of GMOs and radiation (to the detriment of genuine green goals like more wild lands and damping of climate change)”.

Very much alive (i.e. non extinct) blue hyacinth Margaret was present at the event. Photo by the author.

Very much alive (i.e. non extinct) blue hyacinth macaw Margaret was present at the event. Photo by the author.

George Mallory was a mountain climber and one of the English pioneers to Mount Everest expeditions on the 20’s. Why take on such endeavor? It was risky, challenging, and with no direct application. So, “why climb the Everest?”, he was asked.

“Because it is there.”

Sometimes it is all the motivation we need.

To infinity and beyond: what I learned in Cape Canaveral during the NASA SpaceX launch

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SpaceX launch. Photo by the author.

What surprised me the most was the air shaking. When you watch it from TV, you never really expect the atmosphere changing around you. Not only that, but the crowd gasping, shutters clicking, and the PA announcer’s countdown giving you chills. Those experiences are never possible unless you are standing there, witnessing the rocket launch then disappear into the clouds.

I flew to Cape Canaveral last Wednesday as a guest of NASAsocial and sponsored by Owen Software. The rocket launch (SpaceX commercial rocket Falcon9, carrying a Dragon capsule) would take place on Friday. Until then, I’d join in private tours and press conferences.   I was feeling out of place among all the mechanical and aerospace engineers, until I met this guy:

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Simon Gilmore. Photo by the author.

Sorry, I meant THIS guy:

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Aradbidopsis thaliana. Photo by the author.

The press conference on the research experiments onboard Dragon emphasized biology projects – that’s when they started speaking my language. One of the passengers inside Dragon was Arabidopsis thaliana, engineered to be more sensitive to oxygen conditions. Turns out that gene expression in plants is completely different once exposed to microgravity. Which genes are turned off and on? Gilmore’s lab may find out once the A. thaliana comes back from space.

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Michael Johnson. Photo by the author.

We also talked about protein crystals: a brick-shaped rack with 150 proteins (in 10k different crystallization conditions) was being transported on Dragon. Fingers crossed that the astronauts will be able to crystallize those proteins. Back in my day, some people hat to resort to adding cat hair to get a proteins to crystallize (true story). Will adding microgravity do it? Cats may be cheaper than space crystals, but that still won’t crystallize membrane proteins – which may be onboard future capsules.

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Where’s Waldo at Press conference. Photo by NASA.

Along with the other NASAsocial guests, I was taken on a tour of the Vehicle Assembly Building. Please include gasps of excitement:

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In front of the Vehicle Assembly Building

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Vehicle Assembly Building – Interior. Photo by the author.

Which is where I met one of my favorites: the crawler. The largest land vehicle on the planet, responsible for transporting the shuttles from the building to the launch pad. (While leaving a path of destruction behind. Kind of. Its weight completely compresses the road every time it passes by.) Please see chair for scale.

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Crawler at Vehicle Assembly Building. Photo by the author.

All of which culminated in Falcon9 launch on March 1st. It was a visceral experience. I never thought I’d be antsy and nervous listening to a countdown. The 40 minutes I stood there flew by. Next thing I know is: TEN-NINE-EIGHT and dozens of eyes focus on their viewfinders, fingers pressed to the camera triggers. SEVEN-SIX-FIVE and the photographing starts: it is a moment you can’t miss. FOUR-THREE-TWO and the puffs of smoke and engine grumbles tell you it will be soon. ONE — and liftoff.  I take a dozen photographs and stop to watch the show. A show that cannot be reproduced on TV or even in writing.

Anatomically-correct giant heart

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Giant heart at Franklin institute. Photo by Silvana Russo.

I heard the The Franklin Institute in Philly had a giant heart on exhibit.

As a fan of giant hearts, I had to see it.

If I had a giant cabinet in which to store giant hearts specimens, my collection would with a Volkswagen bug-sized blue whale’s heart.

Blue whale's heart model at the Field Museum.

Blue whale’s heart model at the Field Museum.

For context, I would also collect and display the museum ad for the whale’s heart:

A whale’s heart goes for a ride. Photo by Vancouver Science World and Rethink Communications.

A whale’s heart goes for a ride. Photo by Vancouver Science World and Rethink Communications.

And then I’d renovate the cabinet to make room for the Franklin’s giant heart.

Giant heart at Franklin institute. Photo by the author.

Giant heart at Franklin institute. Dr. Silvana Russo analyzes while young museum visitors dash past her. Photo by the author.

I have to confess I was expecting a modest, whale-sized heart. The models of blue whale’s hearts are in high demand and touring the world. They are hollow, so kids can climb in and out through the ventricles and arteries. However, the Franklin’s giant heart was an ambitious model that would belong to a 220-ft giant, someone the size of the statue of liberty.

Statue of liberty’s heart is large enough for adults to climb inside. The mini-tour inside the heart includes micro staircases, claustrophobic spaces, and “you are here”-type maps. The maps convey the analogous heart location you are stepping into (e.g., ventricles, valves, arteries).

I visited the museum with my sister, an MD and blog contributor on the case of debunking House episodes. “We are approaching the lungs!”, she would shout, apparently narrating the tour. I got a little lost in the abstraction – it was hard to tell which valve was doing what and what kind of blood I was (oxygenated?). A whale’s heart might be large enough to make all structures visible and memorable, but not too large as to make you loose the big picture idea.

Dr. Russo (the other Dr. in the family) disagreed. She though it helps giving children an idea of what blood circulation is. I could have interviewed the young participants and ask, but unfortunately they were too scared to get in.

Animal heart display at the Franklin institute. Photo by the author.

Animal heart display at the Franklin institute. Photo by the author.

Near the giant heart were some averaged-sized ones, in a scale of comparison with other animals.

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Average-sized hearts of different animal species. Franklin Institute. Photo by the author.

Most hearts were mammal’s (mouse, cow, polar bear, elephant, and at the top, beaked whale), along with two bird hearts (ostrich and finch).

Dr. Russo tests the circulation exhibit at the Franklin Institute. Photo by the author.

Dr. Russo tests the circulation exhibit at the Franklin Institute. Photo by the author.

Dr. Silvana Russo also tested the Franklin’s interactive exhibit on circulation.

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Dr. Russo tests the circulation exhibit at the Franklin Institute. Photo by the author.

She is the expert and knows how blood drops flow.

Meanwhile, I continue to work on my imaginary collection of anatomically-correct hearts. Valentine’s day seems perfect for that.

New PLOS post: Wildlife documentaries or dramatic science?

I have a new post up at PLOS. This time I look into wildlife films and nature documentaries and analyze if they can teach us something. See below:

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Behind the scenes with To the Arctic 3D. Photo credit: © Florian Schulz/Visionsofthewild.com via Smithsonian blogs.

I first met Chris Palmer when I attended his lecture about ethics in wildlife film. Palmer is a wildlife filmmaker, and his CV includes IMAX productions like Whales and To the Arctic, and the book Shooting in the Wild: An Insider’s Account of Making Movies in the Animal Kingdom. Also a conservation advocate, Chris believes that filmmakers “have a responsibility of raising viewer awareness of the serious environmental problems facing the world”. We talked further (he graciously agreed to answer a few interview questions) and we both agree that wildlife films are great opportunity to educate the general public about science and spread a message of conservation. But, like Chris said, “[solely] promoting the beauty of the natural world is not the same as conservation.” How can we use wildlife films to educate?

Continue reading after the jump.

New post on PLOS blogs: museum education versus consumerism

A whale’s heart goes for a ride. Photo by Vancouver Science World and Rethink Communications.

A whale’s heart goes for a ride. Photo by Vancouver Science World and Rethink Communications.

I have a new post up at PLOS Sci-ed, titled Selling memories: the tenuous line between museum education and consumerism.

A few months ago, the science blogosphere was ablaze with an ad campaign from the a science museum in Vancouver. This campaign combines unusual ads with a quirky scientific message. A sign saying “a blue whale’s heart is the size of this car” is fixed, well, atop of a car. Another car drove around with a “woofasaurus” on the back seat; a fluid-filled tank encouraged kids to walk on water; a tiger’s litterbox littered the street; and a moving squid eye followed museum visitors. All ads promise Vancouver inhabitants that they will find answers at the museum.

As we mentioned earlier (here and here), many adults visit museums after they are persuaded by their children. This phenomenon, called “the nag effect”, is widely recognized and taken advantage of in the world of advertising. One example of the nag effect in action is described in the article “how do children convince their parents to buy unhealthy food.”  The Vancouver Science World and Rethink Communications used the nag effect in their advertising strategy. Their ad campaign, in place since 2004, combined print ads, billboards, bus stop ads, TV and radio spots, and a collection of “unconventional” ad media. Convincing a parent to visit a museum sounds like a better idea than pushing them to buy unhealthy food, but still: we are talking about using the power of advertising and consumerism in favor of a museum.

When is it honorable to use advertising as subterfuge for the cause of science and education?

Continue reading after the jump... 

A little more info on the moa

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Artist rendering of giant eagle attacking unsuspecting moas. Art: John Megahan via Bunce et al, 2005.

Like I said over at PLOS blogs, I first saw a moa fossil skeleton in the Smithsonian’s Museum of Natural History. I was curious about that tall bird with no semblance of wings. I searched for the label to find out if that skeleton was incomplete, in the hope to find more information on that bird’s perhaps long lost wings. It is not uncommon for partial skeletons to be found and displayed – smaller, more fragile bones decompose faster and are not left behind. Many skeletons seen in museums are a collage of bones from many different specimens, and several parts are artificially built (for example, one rib can be a plaster-made, mirror image of another).  However, the label on the moa skeleton explained that this huge bird did not even have vestigial wings. Without the need to fly, its wings completely disappeared throughout the course of evolution. They would have left no trace, wasn’t for the bird’s unmistakable similarity to an ostrich.

The ostrich is today’s largest bird, and it belongs to the ratite (flightless) group of birds. Many species of ratite bird are extinct, including the moa and the elephant bird of Madagascar, but still living are the ostrich, emu, cassowary, rhea, and their tiny relative, the kiwi.

The wiki image above is a great example of the size difference between the kiwi, ostrich, and moa (Dinornis). In fact, the moa was for years believed to be part of the ostrich family, until the little detail of “no wings” came to light. Earlier moa archeologists were surprised after finding one leg bone after the next, but never an arm. One massive bone (which can be seen on the ostrich’s thorax, on the above picture) is missing from the moa and kiwi. That’s a bird’s keel, which is responsible for anchoring a bird’s wings. Many ratites do have wings (like ostriches and emus), even though they are not so helpful. The moa and the kiwi do not.

The moa’s enormous femur bones were first to be found. Twice the circumference of a human femur, those fossils helped recreate the image of this massive bird.  After the discovery of many moa fossil sites and skeleton reconstructions, it is now known that the moa came in 9 species, reached up to 12 ft. tall and could weigh over 500 lbs – heavier than a gorilla. Currently we have an even better understanding of this animal. For example, we can tell its diet consisted of at least 74 different species of plants and that it fought its only predator pre-human settlement (the giant eagle). Researchers have also been able to extract pieces of its DNA from its fossil bones.

Moa long bones (left tibiotarsa) and eggshell, drilled for DNA samples.

Moa long bones (left tibiotarsa) and eggshell, drilled for DNA samples. Alletoft et al, 2011

The moa used to live in New Zealand before extinction, when it disappeared shortly after Maori settlement in the 13th century. This bird was New Zealand’s largest herbivore. There were no land mammals – unless you count the three species of bat. The moa roamed freely, unaware of predators except for giant eagle (Haast’s Eagle). Much like a modern day eagle, it grabbed and killed prey with a strike of its talons – claw marks are preserved in many moa fossils. Moas were easy catch for the settler tribes – having never seen humans before, there was no reason for fearing them. On the course of a few hundred years they were all eaten and only bones were left to tell the story. Imagine the size of those drumsticks: even though moas were eaten, historical reports claim it did not taste so good (and supposedly tasted tough and stringy, and some admit it might have been similar to a kiwi). With no land mammals or other domesticated animals, life in New Zealand must have been difficult. Today however, it serves as an interesting cautionary tale for animal species survival or man-driven extinction.

Now posting on PLoS blogs!

Good news everyone! I’ve been invited by Jean Flanagan and PLoS blogs to join their Sci-Ed team: a blog that focuses on science education. My contribution will be on science education in museums, zoos and aquaria. My first post is up:

It was my third time meandering the halls of the Natural History museum – and first as a volunteer interpreter – when I glimpsed a bird without arms: no wings, no arm bones, no hands, no wrists, and no fingers. Nothing. That skeleton I was seeing had once been a statuesque, NBA player-tall bird. Its neck accounted for nearly half its height; its slender legs, almost the rest, with a globular region in between. That was my first sighting of a moa.

Moa (Smithsonian Natural History Museum). Photo by the author.

The moa is a gigantic extinct flightless bird from New Zealand. Imagine an ostrich, but delete the wings and give it some serious growth hormones. This 12 ft tall, 500 lbs bird was driven to extinction in the early 13th century, when humans hunted and ate them all.

Continue reading after the jump…

For the bio- and anthropologically-curious, I’ll post more info on the moa next week!