Kind Words for Despicable Men (God and White Men–part 3)

For readers today, it is almost impossible to browse through the eugenics literature from before World War II without hearing intimations of Auschwitz in every line. It takes a continual effort to keep in mind that they did not know about the Holocaust then. When one early enthusiast declared that eugenics “is going to be a purifying conflagration some day,” no one understood how horrifically prophetic those words would later sound.

Reading about Irving Fisher, Ellsworth Huntington, and the rest, I felt a predictable sense of loathing: these were despicable men. But in other parts of their lives, even the worst of them was at times admirable, and I felt a queasy sense of liking. This was illogical on a personal level. Their writing was laced with animosity toward the wave of immigrants into the United States after 1890—southern and eastern Europeans (mainly Italians and Jews, respectively), yellow-peril Asians, and the drunken, misbegotten Irish. It was an era when a Harvard anthropologist could lament “the flooding of this country with alien scum.” Fisher spoke of “defectives, delinquents, and dependents.”

Under the pretext of science, the eugenicists were proposing to preserve “Nordic” hegemony by breeding out my own Irish and Italian stock, among others. So why liking? Partly, it’s because the idea of the white Anglo-Saxon gentry prattling about their own superiority has become a stock joke (“Too damned funny, old bean”). Ellsworth Huntington sounds about as dangerous as Henry Higgins in My Fair Lady when he declares: “An Englishman likes to work things out for himself, and is glad when an emergency throws him on his own resources. The Mediterranean and Alpine people, on the contrary, are much more docile, more willing to be led.”

And partly it’s because, having grown up Irish and Italian, I am aware that my people also entertain notions of our magnificence. Other ethnic groups do the same, though they are generally not so foolish, or so accustomed to power, as to issue scientific pronouncements on the topic to the less fortunate. The truth is that all humans favor in-groups, starting with the family, and we disparage those we perceive as outsiders. Treating this as only the outlaw impulse of eugenicists and Nazis is a convenient way of overlooking a hateful tendency in us all.

Madison Grant

These eugenicists also felt disturbingly familiar in other ways. They weren’t sinister characters out of some darkly lighted noir film about Nazi sympathizers, but environmentalists, peace activists, fitness buffs, healthy-living enthusiasts, inventors, and family men. If Madison Grant had not been such an ardent racist and so closely tied to Nazi genocide, he might be remembered today as one of America’s greatest conservationists. “Among his many accomplishments,” writes Jonathan P. Spiro in his recent biography, Defending the Master Race, “Grant preserved the California redwoods, saved the American bison from extinction, founded the Bronx Zoo, fought for strict gun-control laws, built the Bronx River Parkway,” and helped create Glacier, Denali, and Everglades National Parks.  (To be continued.)

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)

Scourge of Africa (Ivory Conclusion)

The trade eliminated elephants from vast swaths of East Africa.   ”People talk as if the ivory of Africa were inexhaustible,” an English explorer wrote in the 1870s.   “Let me simply mention a fact.  In my sojourn of fourteen months, during which I passed over an immense area of the Great Lakes region, I never once saw a single elephant.”   But back in Connecticut, it was easy to believe otherwise.   “Although fifty thousand animals are annually slain to meet the demands throughout the world for ivory,” a newspaper reported, in a profile of Comstock, Cheney & Co., “there appears to be little danger of decimation, owing to the fact that, in the wilds in the backcountry, hundreds of miles from civilization, elephants are as numerous as flies.”

Ernst Moore’s book Ivory—Scourge of Africa was a remarkably frank account of how his business had devastated the continent.  But when he came to “the question of whether or not the killing for ivory must go on…until the elephant is exterminated throughout the whole continent of Africa,” he could only answer with another question:  “Can we find a substitute for ivory that will give us equal grace, delight, and satisfaction?”  Moore thought no such substitute existed, and that the killing would continue.  Even today some pianists insist on ivory, saying sophisticated modern plastics do not meet their needs.

What ultimately saved the remaining elephants wasn’t conservationist thinking.  On the contrary, it was the decline in demand early in the twentieth century as the phonograph, movies, and other modern amusements began to draw people away from their pianos.

###

Reading about the old ivory trade in the Connecticut River Valley, the wealthy people in Asia who are now driving the demand for ivory might well think:  “The Americans were even worse in their day.  Now it’s our turn.”  But it’s no longer possible to plead ignorance about the effects of the ivory trade, and the moral complications are all too obvious:  News reports continually show us the butchered elephants, and the game rangers and poachers who have died over their bodies.  And what if the last wild elephants vanish from Africa, as now seems possible?  The children and grandchildren of the people who are making it happen will look back on them in horror and dismay.  That’s the real lesson of the Connecticut River Valley.  Those precious and beautifully-carved ivory knickknacks will survive not as symbols of status, but of shame.

The Slave Connection (Ivory part 5)

It’s possible George Read had gone into the ivory business in the first place because he believed it to be free of messy moral complications.   He probably knew of his fellow abolitionist Moses Brown, just up the Boston Post Road in Providence, Rhode Island.  Brown had denounced his own early involvement in slaving voyages, as a young man in his family’s mercantile firm.   But he also made it clear that he regarded ivory as a moral alternative for the Africa trade.

The map of Africa then was a blank, and few Westerners knew where the ivory came from or how it reached the African coast.  That began to change only after 1830, when a Salem, Massachusetts, merchant named John Bertram set up a trading station in Zanzibar, which was to supply the bulk of the world’s ivory for the remainder of the century.  In 1844, a Bertram employee there noted, without comment:  “It is the custom to buy a tooth of ivory and a slave with it to carry it to the sea shore.  Then the ivory and slaves are carried to Zanzibar and sold.”  The slaves, he added, were “discharged in the same manner as a load of sheep would be, the dead ones thrown overboard to drift down with the tide…the natives come with a pole and push them from the beach.”

The trip from the mainland across to Zanzibar was only about 20 miles, but it came at the end of ivory caravans that had often traveled hundreds of miles from the interior.  Arab traders led these caravans deeper and deeper inland, bringing trade goods supplied by the Zanzibar merchants, notably gunpowder and the Massachusetts-made cotton cloth known everywhere as merikani.  In 1848, one of the Connecticut River Valley’s own sons went to Zanzibar to trade cloth, gunpowder and kerosene for ivory.  George A. Cheney, later employed at Comstock, Cheney in Ivoryton, proudly reported that he once purchased 60,000 pounds of ivory brought in by a single caravan.

Back home in Deep River, George Read was certainly aware of delays in getting the ivory down to the coast, because of the resulting fluctuations in supply and price.  But perhaps mercifully, he died in 1859, just as Western explorers in Africa were beginning to reveal the horrific details of the trade.   The standard procedure, they reported, was for the Arab trader to befriend tribal chiefs, use their help to empty an area of tusks, then slaughter their former allies, burn their villages, and chain up the survivors to carry tusks down to the coast.  A French traveler wrote that caravans abandoned their dead and dying to the hyenas.  An English missionary reported that slaves who could no longer carry their tusks were left close to the water so the crocodiles could take them.

In 1882, a missionary met up with the ruthless trader Tippoo Tib as he was leading a caravan down to Zanzibar.   Pairs of slaves carrying tusks were fastened at the neck with wooden poles, the missionary wrote, and “the neck is often broken if the slave falls in walking.”   Many of the women carried babies on their backs as well as a tusk on their heads, and if a woman became too weak to carry both, a trader told him, “We spear the child and make her burden lighter.”

Tippoo Tib’s caravan took more than a year to force its way down to the coast, because a local chieftain named Mirambo had blockaded all trade at Lake Tanganyika.  Ernst Moore, an ivory trader who represented Pratt, Read in Zanzibar, later wrote about the expedition in his 1931 book Ivory–Scourge of Africa:  “During this year and more, when no ivory of consequence was arriving at Zanzibar on account of Mirambo’s blockade, the Yankees in the Connecticut ivory-cutting factories were starving for ivory tusks.  The arrival of Tippoo, with tons and tons of ivory, and the news that he had arranged peace with Mirambo and that the trade route was again open, were hailed with shouts of joy that reverberated from the eastern coast of Africa to the inner shores of Long Island Sound.”

(to be continued)

A Badge of Gentility (Ivory part 4)

For the Victorian era, the piano “a badge of gentility,” as one social observer put it, “being the only thing that distinguishes ‘Decent People’ from the lower and less distinguished … ‘middling kind of folks.’”   Every respectable parlor had a piano, and like television and the computer today, it drew people away from public entertainments and back into the home.  There was, however, nothing passive about it.  “Every American woman feels bound to play the piano, just as she feels bound to wear clothes,” a French visitor reported in 1860.   Men were expected to sing along, or at least clap appreciatively.

Lowell Mason of the Boston Academy of Music had recently launched the “better music” movement, which saw music as the path to “the perfecting of man’s emotional and moral nature.”  For newly wealthy Americans, the piano was the best available means for tapping “what is most deep and holy … in the soul of man,” as another musical proselytizer put it.   Earnestly practiced scales and arpeggios drifting out open windows onto elm-lined streets thus became the standard background music of small town life.

Popular tastes didn’t always follow the edifying path Mason had in mind.  Among the favorite themes in popular sheet music, according to one writer, were “dead babies, crippled children, blessed old decrepit grandparents, dying sweethearts, and ascents into Heaven.”  Even classical performers found gimmicks essential for luring American hoi polloi through the door.  The Austrian virtuoso Leopold de Meyer promised to perform melodies on the piano with elbows, fists, and even a cane.  New Orleans concert pianist Louis Moreau Gottschalk kept audiences awake by playing “Yankee Doodle” with one hand and, at the same time, “Hail Columbia” with the other.  Duly inspired, their many admirers went out to buy pianos of their own.  Like newly wealthy people in the developing world today, Americans yearned for a cultural refinement they could not yet quite comprehend.  Such companies as Steinway, Chickering, Baldwin, and Aeolian (“Yoly-yoly” to immigrant workers back in the ivory factories) rose up to serve that need.

All of them required the exquisite luster of ivory.  “It is yielding to the touch, yet firm,” one writer explained, “cool, yet never cold or warm, whatever the temperature; smooth to the point of slipperiness, so that the fingers may glide from key to key instantly, yet presenting just enough friction for the slightest touch of the finger to catch and depress the key and to keep the hardest blow from sliding and losing its power.”   When Stephen Foster wrote “My Old Kentucky Home,” and when Scott Joplin composed “Maple Leaf Rag,” they played on ivory that almost certainly came from the factories in Deep River and Ivoryton.

By the turn of the century, Pratt, Read was sometimes cutting 12,000 pounds of ivory a month, almost entirely for the piano trade.  Tusks then averaged sixty or seventy pounds apiece, so the Deep River factory by itself accounted for the deaths of well over a thousand elephants each year.   The human toll inflicted by the ivory trade is harder to calculate.  But the explorer Henry M. Stanley once loosely estimated that every pound of ivory “has cost the life of a man, woman, or child” in Africa.  In the Connecticut River Valley, it took a pound and a half of ivory to make a single keyboard.

(to be continued)

The Touch of Ivory (Part 3)

Two tusks, then worth $1500 in Deep River

In truth, ivory was simply another commodity then, and one that seemed to be available in almost limitless quantities. As a result, a retired ivory trader would later write, the children of Deep River and Ivoryton for generations were “born to the touch of ivory and have cut their teeth on ivory rings.”   When I lived there in the 1980s, the old factory was abandoned and no tusks had arrived there in 30 years.  But it was still possible to find people who had grown up like that and gone on to spend their careers working with elephant tusks in the local factories.  I remember one of them who recalled swimming in a local pond with his boyhood friends, at a time when so much ivory sawdust washed down from the factory that it covered them head-to-toe.  “We’d come out looking like the Gold Dust Twins.  My God, how my mother would holler.”

Ivory trinkets still frequently turned up at tag sales, and newcomers restoring old houses were sometimes astonished to discover that their doorknobs had been

made from elephant’s tusks.   One day, an oddly angled glass structure rotting in a side yard caught my attention.  It turned out to be an old bleaching shed, designed for holding racks of cut ivory up to the whitening power of the sun.  At the height of the business, an entire field of these glass houses stood behind the ivory factory, and Read himself kept a careful journal, totting up the 30 days of sunlight needed to turn the ivory white.  “No sun! No bleach day! No nothing!!” he lamented, during a cloudy March of 1852.   But a break in the dreary weather also moved him to exultation:  ”Rejoice!  Oh ye Comb-makers for today are ye blessed with

At the bleaching sheds

sunshine!”

It’s hard for us now to grasp the extraordinary intimacy with elephant tusks that was once commonplace in town.  These days, scientists tracking the illegal ivory trade can map the provenance of a tusk by studying its isotopes, persistent biochemical traces of what the elephant ate and where it lived.   But the old ivory cutters had something like that knowledge in their hands.  They could tell Congo ivory from Sudanese, Mozambique, Senegalese, or Abyssian ivory, Egyptian soft from Egyptian hard, Zanzibar prime from Zanzibar cutch.  They knew it not just by how it responded to their saws, but by how it felt beneath their fingertips.   ”To observe a man at work with ivory,” a reporter who visited the Pratt, Read cutting rooms once wrote, was “to watch a man in love.  As it is sorted, sliced, cut, and matched, each workman actually fondles and caresses it.”

Nobody in the factories would have phrased it quite that romantically.  The work started with “junking” tusks into squared-off cylinders.  A skilled marker then studied each cylinder and drew a precise map on one end to identify the least wasteful pattern of subsequent cuts.  As the ivory went under the saw, a jet of water played over the surface to prevent burning.  Even so, the air in the workrooms was filled with ivory sawdust, and what the reporter called “a penetrating, unpleasant odor not unlike the smell of burning bones.”

“To tell you the truth, I didn’t think much of it,” an old ivory cutter once told me.  “Your hands were in water all day and once in a while you’d hit a pus pocket in the ivory and—whoosh, it would smell.”  Bullets embedded in the tusk were also a frequent hazard.

Every scrap and wedge of ivory got cut into some useful product, from cutlery handles to collar buttons and nit combs (small and fine-toothed for picking lice and their eggs out of the hair).  The sawdust that didn’t wash down into the river served to fertilize tomatoes in local gardens.  “Nothing was wasted out of those damned elephant tusks,” another worker told me.

But what the ivory workers of the Connecticut River Valley came to know best was the art of cutting tusks into narrow, four-inch-long blocks, and wider, two-inch-long blocks.   These blocks then had to be “parted” horizontally into veneers, at a rate of 16 per inch.   The narrow veneers, called tails, were then glued down between the black keys on a piano, while the wider veneers, or heads, went on the front of the piano key, where the fingers touched.  Beginning in the early 1850s, when this country produced just 9,000 pianos a year, the business boomed.  By the peak year of 1910, when production hit 350,000, this country had become the largest manufacturer of pianos—and ivory keyboards–in the world.

(to be continued)

Moral Complications (Ivory part 2)

Read

The father of Deep River was a man acutely attuned to moral complications.   George Read was six feet tall, blue-eyed, clean shaven, and with a quiet, self-effacing manner.  As a young man at the beginning of the nineteenth century, he built a dam on the village’s namesake river, with a waterwheel to drive the saws in a small shop.  There a couple of men cut ivory into hair combs and other knickknacks.  Working with elephant tusks was already a local industry, probably through trade between the Connecticut River’s coastal sea captains, and the trans-Atlantic merchants in New York, Boston, or the Caribbean Islands.  But Read found a way to build his business into a major company, and it would eventually employ hundreds of local residents.

He was a deeply scrupulous man on the familiar New England model, a careful steward of time and money, practical and relentlessly industrious.   At a time when a fortune of $100,000 made a man rich, he believed that “no Christian man ought to accumulate over $25,000,” and he was apparently generous enough to live and die by this rule.  He made the rounds of the village several times a day to keep tabs on its progress, and he founded the Baptist church, the local bank, and the town cemetery. At one point, his wife mentioned to him that the townspeople were gossiping about some transgression he had supposedly committed, and Read replied with a characteristic blend of reticence and quick conscience, “No, I did not do that, but I do worse things.”

Read’s strong sense of moral responsibility led him to become an abolitionist, at a time when it was still dangerous to do so.   There was a risk that Southern customers might shift their business to ivory companies in England, and even in Connecticut itself, where slavery was not entirely abolished until

Winters

1848, riots sometimes broke out when anti-slavery activists spoke.  But Read was already an active stationmaster on the Underground Railroad in 1828, when a fugitive slave from the Carolinas showed up at his door seeking refuge.  Billy Winters, a name given to protect him from recapture, remained in the Read family home for the next 20 years and went to work in the ivory business.  Read founded the local branch of the Anti-Slavery Society, which had more members in the backwater village of Deep River than in New Haven.  He seems never to have recognized a horrible irony:  His own business depended entirely on slave caravans to carry the tusks from the African interior down to the coast.

(to be continued)