The Earth Moved

This is a story I wrote for the June issue of Smithsonian Magazine.  The editors there asked me to write a different lead, to make it seem more timely.  You can read that version here.  But I think the historical account stands on its own.  Feel free to disagree in the comments:

Alfred Wegener

On November 1, 1930, his fiftieth birthday, a German meteorologist named Alfred Wegener set out with a colleague on  a desperate 250-mile return trip from the middle of the Greenland ice pack back to the coast.  The weather was appalling, often below minus-60 degrees Fahrenheit.  Food was scarce.   They had two sleds with 17 dogs fanned out ahead of them, and the plan was to butcher the ones that died first for meat to keep the others going.

Less than halfway to the coast, down to seven dogs, they harnessed up a single sled and pushed on, with Wegener on skis working to keep up.   He was an old hand at arctic exploration.  This was his fourth expedition to study how winter weather there affected the climate in Europe.  Now he longed to be back home, where his wife Else and their three daughters awaited him.  He dreamed of “vacation trips with no mountain climbing or other semi-polar adventures” and of the day when “the obligation to be a hero ends, too.”   But he was also deeply committed to his work.  In a notebook, he kept a quotation reminding him that no one ever accomplished anything worthwhile “except under one condition:  I will accomplish it or die.”

That work included a geological theory, first published a century ago this year, that sent the world woozily sliding sideways and also outraged fellow scientists.  We like to imagine that science advances unencumbered by messy human emotions.  But Wegener’s brash intuition threatened to demolish the entire history of the Earth as it had been built up step by step by generations of careful thinkers.  The response from fellow scientists was a firestorm of moral outrage, followed by half a century of stony silence.

Wegener’s revolutionary idea was that the continents had started out massed together in a single supercontinent and then gradually drifted apart.   He was of course right.  Continental drift, and the more recent science of plate tectonics, are now the bedrock of modern geology, helping to answer life-or-death questions like where earthquakes may hit next, and how to keep San Francisco standing.   But in Wegener’s day, drift was heresy.  Geological thinking stood firmly on solid earth, continents and oceans were permanent features, and the present-day landscape was a perfect window into the past.

The idea that smashed this orthodoxy got its start at Christmas 1910, as Wegener (the W is pronounced like a V) was browsing through “the magnificent maps” in a friend’s new atlas.

New Hope and More Hard Work (A Bitter Pill–Conclusion)

So where does all this leave drug research from the natural world?  Miller, Vederas, and a few small drug companies remain surprisingly optimistic.   That’s partly because the resource, though rapidly dwindling, is still out there waiting to be studied.  Miller estimates that medical researchers have tested only about 60,000 of the 400,000 or so plant species on Earth, and most of those against only a handful of diseases.  Extrapolating from the past success rate, he estimates that the plant species still waiting to be studied may contain upwards of 500 new botanical drugs.

Moreover, new technologies are making it easier to find them, according to Vederas.  Automated fractionation can now rapidly break down botanical specimens, thinning out the natural complexity to just three compounds per test well for high throughput screening.  Better methods also make it easier to synthesize these compounds, leading this past November to approval of a new breast cancer drug, Halaven, derived from a sponge found on the coast of Japan.  Researchers are also learning how to clone and work with individual genes in a plant.  At the University of California at Berkeley, for instance, Jay Keasling’s laboratory has recently overcome obstacles to transferring plant genes into bacteria and fungi, for synthetic production of the highly effective anti-malarial artemisinin, from the sweet wormwood plant.  He says commercial production will begin this Autumn.

At the same time, many of the remarkable biochemical functions attributed to plants and animals are turning out to come not from the organism itself, but from the bacteria and other microbes around it.  Instead of having to plant fields or cut down forests to get medicinal compounds, drug companies may soon be able to have these microbes brew them for us in fermentation vats.  Such improvements could lead to what Miller calls a “second renaissance” in natural products drug development.  Ethnobotanist Mark Plotkin, an early proponent of bioprospecting, adds, “Just because capitalism doesn’t get something right, doesn’t mean it’s not there.  We know that well these days.  You need to look everywhere, but I think the sweet spot lies somewhere between the medicine man and the microchip.”

This is not to say that blockbuster $1 billion-a-year drugs are ever going to produce a steady flow of cash for habitat preservation.   

Nature Isn’t Simple (A Bitter Pill-Part 4)

A plant sample—even something as basic as coffee or tea–may contain thousands of compounds.  In the lab, chemists “fractionated” plant samples, breaking them down into crude extracts.  But they still ended up with hundreds of compounds in each of their 1536 test wells.   “This is where the wheels fell off of this thing,” says Paul Armond, a plant cell biologist who spent 30 years in drug development at Pfizer.  “High-throughput screeners hated these samples.  They didn’t want to have anything to do with them because even if you got a hit in one of these fractionated samples, you didn’t know which of the hundred compounds in the test well was the active one.”  A high-throughput screener’s job is to test as many compounds and get as many hits as possible, and natural compounds just seemed to clog the pipeline.

Even if they managed to isolate an active compound from a plant, says Armond, “it would be, from the organic chemists’ point of view, some ugly compound, this big, giant molecule that no chemist could ever possibly synthesize.   They‘d said, ‘What am I supposed to do with this?’”  When a compound seems promising, the usual next step is to “add things to it, take things away, rearrange things, and find where the important parts of the molecule are and where the not-so-important parts are.”  Through the magic of combinatorial chemistry, researchers can target the molecule more carefully, or weed out unwanted side effects.  But if a compound from a natural product is too complex to synthesize in the first place, “then you can’t do any of those things.”

One final obstacle made natural products problematic: 

Horror Stories and High Tech (A Bitter Pill–Part 3)

So each new negotiation starts from scratch and can entail months or even years of “significant legal and travel expense, all before a single collection is made,” says Miller.  The uncertainty of these negotiations “may be more of an impediment to pharmaceutical companies,” he suggests, “than the actual commitment to share potential profits.”

Horror stories abound:  In the late 1980s, a U.S. National Cancer Institute team was working in the West African nation of Cameroon on a compound that looked like the cure for AIDs.  “This was a plant that was still eating research dollars at an enormous rate, it wasn’t making any money, and, man, the Cameroonians were all wanting to buy themselves new Mercedes.”  Though the researchers had an access agreement with one government ministry, “about five other ministries stood up and said, ‘Oh you should have signed that with us.’”  Then they bickered.  Even if the compound had proved to be the cure (it turned out to be too toxic), “I’m not sure we would have been able to work on it,” says Miller, “because the Cameroonians put such tight clamps on it.”

But drug companies also botched their bioprospecting efforts through a combination of financial and technological hubris, critics say.  The financial side is a familiar story of senior executives focusing on quarterly growth at the expense of science.  Getting a new drug to market, says John C. Vederas, a medicinal chemist at the University of Alberta, “requires a lot of creativity and intellectual input and study and time and money”—on average ten years and $1 billion worth of research.  Boosting revenues by buying up other large drug companies can look like a quicker way to keep Wall Street happy.  And with each round of consolidation, company leaders “basically layoff employees, close research and development units that have a long record of being successful, and buy technologies that look promising from smaller companies.”

Beginning in the late 1980s, big drug companies also increasingly diverted their research dollars from natural products to combinatorial chemistry and high-throughput screening.  That is, they turned to automated methods to bang out large libraries of closely related synthetic compounds.  Then they sorted out the biologically active ones by running these compounds through a device the size of a hardcover book, with 1536 little plastic wells, each containing a different bioassay.  It’s a “brute force method,” says Vederas, and can take a million tries to produce one promising lead.  But the numbers may still seem to work because automation makes those million tries relatively cheap.

Natural products didn’t fit the new technology.

(to be continued)

How The Bioprospecting Bonanza Went Bust (A Bitter Pill–Part 1)

This is a cover story I wrote for the spring issue of Conservation Magazine:

Twenty years ago this past October, environmentalists around the world celebrated a landmark deal between a major drug company, Merck, and Costa Rica’s National Biodiversity Institute, INBio. Until then, the standard practice had been for drug companies to collect biological specimens anywhere they wanted, ship them home to study, and (if they were very lucky) develop one or two of them into miracle drugs—all without the source country ever being aware of it. But instead, Merck was now paying $1.1 million up front for bioprospecting rights and promising a royalty from any drugs that resulted.

For environmentalists, the best part of the deal was that a share of any payment would go to protect the habitat itself. The rest of the world was furiously demolishing forests and wetlands, converting them to short-term cash crops like soybeans, hamburgers, and shrimp. But suddenly, a Fortune 500 company was putting money behind the idea that nature intact might have a higher value. One economic analysis even put a number on it: bioprospecting for drugs would increase the value of some habitats by more than $3,600 an acre.

Other economists warned the added value was likely to be no more than $25, but the dream of earning “green gold” by tapping “the mother lode in Mother Nature” quickly spread worldwide. In Rio de Janeiro in June 1992, the Convention on Biological Diversity for the first time recognized the need to preserve a multitude of habitats and species as a matter of both international law and the good of humanity. It also stipulated that a fair share of the benefits should go to the countries where this diversity flourishes. It seemed like the beginning of a new era in drug discovery, international development, and habitat preservation alike.

It was also too good to be true. In 2008, Merck quietly abandoned its search for new drugs from the natural world, shifting its attention to synthetic compounds and vaccines instead. Then last year, as if to mark the anniversary of its Costa Rican folly, the company gave away its entire library of natural compounds—100,000 extracts representing 60 percent of all known plant genera, ready to be screened for the next big miracle drug. And it wasn’t just Merck: Pfizer, Eli Lilly, Bristol-Myers Squibb, and most other Big Pharma companies have also abandoned the direct search for drugs from the natural world. “We lived under the assumption that the rainforest was full of medicinally useful compounds like vincristine,” says James Miller, vice president for science at the New York Botanical Garden. Derived from a plant in Madagascar, the rosy periwinkle, that drug had turned leukemia and lymphoma into survivable diseases. “And nobody found the next vincristine.”

Miller holds out hope that drugs from the natural world may yet have their day. But bioprospecting since the Merck deal has so far failed to produce a single new blockbuster drug. Instead of the widely anticipated golden age of drug discovery, new drug approvals over the past decade have sunk to a 25-year low. Nor has any major drug contributed revenues to the preservation of the habitat from which it was originally derived. On the contrary the Convention on International Trade in Endangered Species says 64 plant species are currently threatened by overharvesting for medicinal uses.

What went wrong?  (to be continued)

Off The Map

Suriname Wildlife, as depicted by Maria Sibylla Merian, the German artist and naturalist in the eighteenth century.

I arrived last night in Paramaribo, Suriname, to join an expedition in search of new species, in the unexplored southeastern corner of the country, deep rainforest on the northern border of Brazil.  It’s a big expedition, including 20 or so scientists from all specialties, and also requiring lots of logistical advance work.

A Cessna Caravan will ferry us out Thursday from the capital city of Paramaribo maybe 175 miles south to our jumping off point at Palumeu.  Then on Friday, we’ll travel by helicopter over the Kasikasima outcrop out to our first research camp, where an advance party should have cleared a heli-pad out of the forest.  After nine days there we’ll traveling down along the Palumeu River to a second camp for a six-day stay.

But there are lots of uncertainties in this kind of trip.  We’ll also be out of internet contact till the end of the month, though it may be possible to send Twitter messages out via satellite phone (you can follow me @RichardConniff).

Meanwhile, I’m taking in Paramaribo, and thinking about early explorers like Maria Sybella Merian, an eighteenth-century artist, who painted one of my favorite images of Suriname wildlife (above), a blend of fantasy from the Bestiary era with the astonishing real-world finds of the Great Age of Discovery.

Also thinking about John Stedman, a mercenary who came here in the eighteenth-century as part of a Dutch expedition to suppresst runaway slaves.  I wrote about him in The Species Seekers:

Stedman

Stedman’s colorful memoir was a bestseller of 1796, under the ponderous title Narrative of a Five Years’ Expedition against the Revolted Negroes of Surinam, in Guiana, on the Wild Coast of South America, from the year 1772 to 1777. The book was partly a picaresque adventure tale, told on the ribald model of Henry Fielding’s Tom Jones. It was also an indictment of slavery, though the author was hardly an abolitionist.  And, oddly, it was a celebration of South American wildlife.

The mix of elements could be jarring.  Along with an account of how a planter’s jealous wife had slit a slave girl’s throat, stabbed her repeatedly in the breast, and tossed her into a river with hands bound behind, Stedman also offered his readers loving descriptions of spider monkeys, flying squirrels, cockatoos, and coatimundis.  One illustration, by Stedman’s friend, the poet and artist William Blake, depicted a slave hung from the gallows, still living, by a hook jammed under his ribs, and the next showed

Spur-winged water hen

“The Toucan and the Fly-catcher.” After “Flagellation of a Female Samboe Slave,” the reader could contemplate “The Spur winged Water hen” and “the Red Curlew.”

Taking delight in the natural world was a way of coping that suited Stedman’s “incurable romanticism,” according to the historians Richard and Sally Price.  His descriptions of the natural world were vivid enough that they may have served as a source for Blake’s famous verse “Tyger! Tyger! Burning bright/In the forests of the night …” (Stedman wrote of a “Tiger-cat,” or jaguar, “its Eyes Emitting flashes of lightning.”)

Everybody’s a little nervous about the expedition ahead, but also excited.  At lunch today, one of the scientists was talking about having once previously had a chance to visit a place like this, so untouched that the animals came close, curious, and unafraid, not knowing yet what humans could be.

Three Meals Away from Anarchy

The Ecologist, a British magazine, has an intriguing interview with theologian Martin Palmer.   He’s co-founder of the Alliance of Religions and Conservation (ARC) and his book Sacred Land (Piatkus) came out yesterday in the United Kingdom and appears to be available on Kindle. He has some good, contrarian stuff to say about our global rush from the countryside into cities, and also about the  misguided inclination among environmentalists to justify protecting the natural world on utilitarian grounds.  Here’s an excerpt from the interview:

You mention the abandonment of London in past crises, do you think cities are particularly at risk?

One of the trends that most alarms me about contemporary thinking, say within the United Nations, is this drive to speed up the movement of people from the countryside into the cities so that you can industrialise the countryside. If you’ve got the people in the cities, the theory goes that it’s much easier to supply them with food, warmth and energy, and you industrialise nature.

But cities live off the countryside, not the other way round. Think of all the great disaster movies: they’re right. What will happen in a crisis is everybody will try and escape to the countryside. We are almost wired to relate survival and sustainability with not being in cities. Building the mega-cities where you rely upon transport to get you 30 miles from your suburb into the middle of Shanghai, or where you rely on airplanes bringing you orange juice from Kenya into central London, nice, but not sustainable. It’s so fragile, we saw that with the Volcanic ash incident two years ago, in one week we had people in complete panic.

If you get a collapse in nature, and the only communities you’ve got are huge and entirely reliant upon a tiny group of workers to provide food, clean water and energy, if those groups are affected, if there is a collapse, if you can no longer transport food, no longer grow the food, if the soil is eroded, if the Sun’s gone because of volcanic ash or even our own activities and disasters, then those communities have no ability to actually eat anything on the land. And if you look at all the great collapses of civilisations, it’s the cities that go first. There was a very famous statement by the Archbishop of Canterbury in the Second World War, William Temple, and I think it sums it up, ‘we are only 3 meals away from anarchy.’ if you’re heading towards your third missed meal and there’s nothing in the local Tesco express, what do you do?

How important are both the countryside and nature to human existance?

I think knowing about the countryside is crucial because we are a grazing species and in order for us to graze, we need the crops and the materials to graze upon. And the destruction of the countryside, whether that’s through urbanisation, industrialisation, soil erosion, deforestation, it’s almost like a suicide pact. We need this to sustain us. But also we are a species that has the capacity to wonder. One of the great mistakes in the environmental movement is to become utilitarian. To argue for example that why we keep the Amazon is because it’s a carbon sink. Well, maybe it’s the fact that a third of all species live in the Amazon is another reason for preserving it. Yes, we need the countryside and we need nature to keep us alive, but we are not the only creatures on this planet that have the right to be fed and kept alive by nature as part of nature.

I think we’ve got to start shifting the discussion away from ‘what can we do to survive?’ to ‘what can we do to ensure that nature survives, and therefore, we survive?’ I think we have to remember we are a wondering species, we are the ones that gaze the stars and wonder who the hell we are, we are the ones who sit by the sea and look at the infinity of the sea disappearing into the horizon and see that as a metaphor for our own lives. And at the moment we purely become concerned with nature as something that sustains us, rather than feeds us spiritually, psychologically and emotionally, I think we’ve lost the plot.

 

Kickstarter for a Species Seeker

I’m borrowing this, with thanks, from Bug Girl’s Blog because it’s a great cause.  I’ve traveled with Brian Fisher and his team as they hunted for new ant species in Madagascar, and they do great work.  You can read that story here and in my book Swimming With Piranhas at Feeding Time.  I’m also a fan of Kickstarter, the fundraising site for creative projects.  My daughter recently raised funds there to do an art project about my father as an Outsider Artist.  So it’s great to hear that crowdsource project funding has now come to science, too:

Earlier this week, the internets were buzzing with a claim that Kickstarter is funding more projects than the National Endowment for the Arts.  It turns out that may not be strictly true, but it certainly is true that a lot of cool projects are being crowd-sourced that otherwise would never have made it off the ground.

I’ve mentioned some insecty Kickstarter projects before, like Meet The Beetle (a film about an endangered tiger beetle).  Unfortunately, Kickstarter is limited to arts and humanities. But now the concept of crowdsourcing has been harnessed for science!

Petridish.org is so new it hardly has a bacterial film growing on its website yet. Its first science crowd-sourcing project involves two awesome things: Insects and Madagascar.

“Unique” doesn’t begin to describe Madagascar. This giant island split from the African Continent over 160 million years ago, and over 90% of it’s mammal and reptile species occur no where else in the world.  Deforestation and erosion are critical threats to the island’s ecosystems, and many native species are endangered.

Brian Fisher, one of the folks behind AntWeb, is leading a project to document the ant species of a high remote preserve.   You might be wondering why you should care about ants in Madagascar.  You may especially be wondering this because you have figured out that at some point later in this post I’m going to hit you up for a donation.  I really like this statement from AntWeb that puts ants in context:

“At this moment, more than one thousand trillion ants are scurrying all over the Earth. If every human climbed aboard one side of a scale, and every ant crawled onto the other side, the scale would just about balance.”

Ants probably move more earth and recycle more dead things yearly than a whole army of human undertakers with bulldozers ever could.  Ants are a critical part of making the world’s living systems function.  The project description:

“Ants are the glue that hold forests together. But Madagascar’s hotspots of biodiversity are vanishing, and along with them unknown species. An estimated 40 percent of the island’s species, in fact, have already perished through human encroachment.

Pyramica hoplites stalks other insects in the leaf litter like a miniature jaguar. "If your sister goes to the corner for a glass of milk and never comes back, it's Pyramica that got her," says Fisher.

While ants aren’t as popular as furry and feathery animals, the insects turn over forest soil, breakdown debris, disperse crucial nutrients and otherwise support an unimaginable number of species both up, down and across the food chain. The insects are also a growing resource for antimicrobial and antifungal compound discovery, as many ants manufacture such chemicals to ward off disease and even farm food.

I need to reach one of the last standing pristine forests, called the Kasijy, before nearby populations burn them down to raise cattle. Researchers have visited the remote site only a handful of times because it’s a rugged, canyon-filled landscape resting on high blocks of limestone and sedimentary rock.Because Kasijy is so pristine, it also serves as a crucial data point of what Madagascar used to be like before the advent of modern civilization. The region and other forests are great places to understand the ongoing impacts of climate change on highly specialized ecosystems.

My expedition aims to:

• Inventory Kasijy’s untold new species and document their roles in a pristine natural ecosystem.
• Understand the biodiversity patterns of Madagascar and resolve our “bioilliteracy” of the Kasijy forest.
• Set up more robust conservation plans for the island.
• Raise awareness of Madagascar’s natural wonders and its ongoing plight.”

There are 39 days left to fund this project–I hope you can spare a dollar or two to help a researcher out!  Note that a large gift gets you acknowledged in any manuscripts published from this research.

And for a mere $5000, you can buy scientific immortality with your name, or the name of a friend or loved one, on one of Fisher’s new species.  Whatever you give, Fisher will not waste your money.  When I was there, we jumped a freight train to get to a research site, and he seemed to live on rice, a little chicken, and a horrible tea made from the burnt leavings at the bottom of the rice pot.

Nature Is Vanishing from Kids’ Books

One of my favorite things when my children were young was reading them Where The Wild Things Are, over and over, with lots of sound effects for the wild ruckus among the animals.  But a new study, looking at Caldecott Prize winners from 1938 to 2008, suggests the natural world is vanishing from children’s books.   The study appears in February’s Sociological Inquiry, and gets a write up in USA Today:

•Early in the study period, built environments were the primary environments in about 35% of images. By the end of the study, they were primary environments about 55% of the time.

•Early in the study, natural environments were the primary environments about 40% of the time; by the end, roughly 25%.

Images of wild animals and domestic animals declined dramatically over time, says lead author Al Williams of the University of Nebraska-Lincoln. “The natural environment and wild animals have all but disappeared in these books.”

Co-author Chris Podeschi of Bloomsburg University of Pennsylvania says, “This is just one sample of children’s books, but it suggests there may be a move away from the natural world as the population is increasingly isolated from these settings. This could translate into less concern about the environment.”

Not to mention the terrible loss to parents and young children.

You can read the full study here.

Insect Paranoia

I was visiting author and entomologist May Berenbaum recently at the University of Illinois in Urbana-Champaign, and her collection of old insecticides caught my eye