Friday, July 1, 2011

In praise of curiosity: Evelyn Glennie

A good friend of mine shared this video of Evelyn Glennie's TED talk with me a few months back, and I've been meaning to post it. Listening to her could be one of the best things you do with the next eighteen minutes. 


Culling geese

The New York Times reported recently on the generosity shown toward turtles nesting at JFK. Apparently there is a bitter dispute going on in the NYC community about how officials treat geese, however, and a comment had led me to look further into the issue. The comment thread revealed some of this bitterness, and I had wanted to give a fuller response than I could fit into the comment box, so I post it here:
Brian (#47): I appreciate your responding to clarify your position. You seem firm that the geese must be culled. This was not clear from your earlier comment, which didn't even mention culling—in fact, I didn't know about the culling until Ellie's comment prompted me to wonder what she meant by saying that "geese are a whole different story." (So at least one person here did not know what she was talking about.) It seems the debate is, at root, a conflict between moral perspectives on how we interact with the rest of our ecosystem.
As for your implicit accusation that people who object to the culls are mawkish sentimentalists, and that "the real problem" lies with them, I'd like to point out that the New York Magazine article quotes the president of the Humane Society as agreeing that there is a problem (and even helping with the egg-addling) but also criticizing the USDA for being historically inclined to kill animals. He then notes a successful relocation program that took place with gulls near JFK in the 90’s.
Here are some facts from the same article, which I'll assume for argument's sake are correct: in 2010, the geese numbered ~257,000 in NY state. 15,000-20,000 Canada geese currently live year-round in the metro region. Over the past three decades, there have been “as many as” 315 bird-plane collisions each year.  The USDA decided, by methods not described, that a mere 5000 birds is an “acceptable” number.  If they mean to leave 5000 in NY state, that’s quite a massacre they propose; if they mean only in the metro area, that’s still a significant cull. The article doesn’t mention the number of planes that fly over the city, but 300 collisions actually isn’t much—and even if you kill birds that are nesting near the airport, this doesn't do anything to reduce the risk of migrating (non-NY-resident) geese getting sucked into plane engines. In fact, the famous Sullenberger landing in the Hudson River was forced by just such migrating geese.  
Furthermore, it is valid to ask whether culling birds on Riker’s Island and Prospect Park is going to do much to reduce an already-low risk: a report covering 1912-2002 estimated that bird strikes cause 1 human death per 1 billion flying hours. Air travelers face greater danger from a plethora of other possible events. Needless to say, the birds come out much worse.
I have several objections to the culling described in the article, some moral, some practical, and some a mixture of both. The most salient here is the tremendous waste of it all: as the article notes, there are “...alternatives which are probably much cheaper and more environmentally friendly than sending hundreds of adult geese to suffocation chambers, double-bagging their carcasses, and dumping them in a landfill.”  (You know something is morally objectionable when "suffocation chamber" becomes an acceptable euphemism for "gas chamber.") Apparently I’m not the only one troubled by this waste: a June 15 cityroom article in the NY Times informs us that this year, the culled geese are at least going to be sent to slaughterhouses in PA and distributed to food banks. 
One last point. We define “pest” rather arbitrarily as anything that competes with us. Yet humans are responsible for soil degradation and contamination, massive deforestation, the eradication of 50% of ocean-dwelling species in just the past half century, the slow suffocation of trees* and a host of other environmental catastrophes. We have also shown remarkably poor prognostic ability when manipulating species to try to control some small part of nature in one region, which invariably has profound and unpredicted consequences elsewhere.  I’m not sure we can afford to be killing off massive numbers of animals when we have no idea what the effect on the ecosystem will be. In any case, if we wait long enough, the geese will die off on their own through some combination of effects of toxins in the environment and climate change. Then again, so will we. So maybe we should be focusing on bigger problems.

*The entire earth has effectively become a gas chamber for trees: go to Wit's Endclick on links for research about dying trees, and get very, very depressed. 

Saturday, June 25, 2011

Marriage equality comes to New York

New York just became the sixth (and most populous) state to grant marriage rights to gay couples. Now it seems that the only people who remain politically and economically disadvantaged are single renters, who contribute comparatively little to the wedding, childbearing/rearing, and mortgage industries. (In a nation of "consumers"—the preferred American descriptor for what other democracies call "citizens"—it is the size of one's economic footprint that matters, not one's ecological footprint.)[1]

It's a bit ironic that gay couples have fought so hard to enjoy the social legitimacy of a contractual relationship that has so often spelled hierarchy and inequality for the participants. (A recent New Yorker cartoon shows two men in a domestic scene, with the apron-wearing partner saying he wants equality in marriage.) Perhaps this is what really frightens religious homophobes: the possibility that gay marriage will undermine the structural inequality that the religious right believes proper for heterosexual relations. Heterosexuals should be so lucky!  I have gay friends who have been more happily married, and for more years, than many straight couples; I also have gay friends who feel ambivalent about the institution of marriage while still applauding New York's decision, given the socioeconomic realities of contemporary life. One gay friend wrote wistfully of the days when to be gay was to be an outsider, anti-bourgeois; I know several who view the desire of so many gay couples to have children as a mere ploy for social acceptance or, at best, a result of straight culture's brain-washing.

Although I do not have children myself and believe that dominant narratives should always be scrutinized, I think this particular view condemns with too broad a stroke. There are certainly wrong-headed motives for having children—to seek cultural legitimacy, personal validation, or unconditional love (any of which is sure to backfire when said children are born) — but there are generous motives, too.  Any sensitive, thoughtful person, gay or straight, could conceivably want to provide love and guidance to a vulnerable young human, and the world contains far too many unwanted children who desperately need to be adopted into loving homes. Rescuing such children from a life of feeling unwanted and alienated is a noble endeavor, and perhaps no one is better suited to the task than someone who has experienced such wounds and managed to learn, from examining their own suffering, how to strengthen others.

In a similar vein, there's a difference between those who yearn to spend their lives freely and openly with the person they love and those who seek to marry simply because it is expected, all their friends are doing it, or their parents are pressuring them. A case could be made that people who have long been deprived of a right are that much more appreciative of it—there is, in fact, evidence that granting marriage rights to gay couples, who divorce less than heterosexual couples, actually reduces the divorce rate among heterosexuals as well. (Not that we should make too much of statistics, for they tell only a small part of any story.) And it surprises many people to learn that there is a long history of gay marriage in other cultures and historical periods, dating from the ancient Greeks and continuing into the 18th century among Native American tribes [2]. To ignore this history, not to mention the equally long history of long-term heterosexual love, is to disdain those relationships that do endure, among humans as well as many other species.

Human motives are complex, however, and, often as not, confused and opaque even to the most introspective among us.  All I can say is that it is best to carefully consider why we want to marry or not marry, to have children or not, and to make sure that when we undertake actions that necessarily and profoundly affect another sentient being we consider the consequences with a rigor as robust as the passion we feel [3].  Here we can find inspiration in two poets, one 19th century German (Heinrich Heine) and one 20th century American (Dorothy Parker), who achieved crystalline clarity about what they wanted from marriage:

Die Heimkehr [4]

Und bist du erst mein ehlich Weib,
Dann bist du zu beneiden,
Dann lebst du in lauter Zeitvertreib,
In lauter Pläsier und Freuden.

Und wenn du schiltst und wenn du tobst,
Ich werd es geduldig leiden;
Doch wenn du meine Verse nicht lobst,
Laß ich mich von dir scheiden.


If you shall be my faithful wife
Then fortune on you shines.
You'll live a gay and carefree life
Of leisurely pastimes.

And if you scold and if you rave
I'll abide it all with pleasure.
But if my poems you will not praise
Then let us split forever.

Fighting Words

Say my love is easy had,
Say I'm bitten raw with pride,
Say I am too often sad—
Still behold me at your side.

Say I'm neither brave nor young,
Say I woo and coddle care,
Say the devil touched my tongue—
Still you have my heart to wear.

But say my verses do not scan,
And I get me another man!

May we all find an appreciative audience, whether straight, gay, or ameobic.



[1] The economic impact of this decision was not lost on anyone: marriage (or, rather, weddings) are projected to add $142 million to the NYC economy and $184 million to NY state as a whole. Another angle that should not be overlooked: this is the first time gay marriage has passed in a state where one of the houses was controlled by Republicans. Back in 2009, when Democrats controlled the state house and senate, the gay marriage bill was roundly defeated (by 14 votes).  On Friday, the bill won by a four-vote margin (33 to 29). 

[2] That is, before Protestant Europeans dedicated themselves to imposing gender dimorphism on the "savages" who were otherwise living happily with each other and the rest of the natural world. So much for progress.  See, for example, Michael Bronski, A Queer History of the United States (2011), and Intimate Matters: A History of Sexuality in America, John d'Emilio and Estelle Freedman (1988, 1997). The latter book is a classic and was cited by Supreme Court Justice Anthony Kennedy when he struck down a Texas law criminalizing sodomy.

[3] This includes the decision to acquire a pet. Today I was walking down a Manhattan street and saw a young couple, probably in their twenties, stepping out of a souped-up black car to deposit a tiny, and I mean tiny, pit bull puppy on the sidewalk. I had the impression they wanted it to "do business" but the poor thing looked lost and very fragile. I asked how old it was as I stooped down to give it some affection and protect it from the stark sun, if not the heated pavement; the young man, thick arms crossed in front of his capacious chest, said "almost 4 weeks." I tried to suppress my horror and said that was awfully young. The man, this boy, really, mumbled, "it's ok, we have a book... we give it milk." I dared not ask what kind; images of chocolate and strawberry milk cartons popped into my head.

I pointed out that puppies need more than milk from their mother, and continued supporting this tender little fellow whose cerebellar development was so incomplete he could barely stand without wavering. Or maybe he was dehydrated: he tried to suckle my finger, and the boy gruffed, "no biting," to which I replied that he might be hot and thirsty. Hefty boy was unimpressed.

Puppies should not be taken from the mother before 8 weeks; 10 weeks is even better, and frankly, we don't know how much better it would be if we didn't make a habit of breaking up canine families at all.  (A famous wag once wrote that the only reason dogs hadn't yet acquired language is because we take them away from their families so young.) I really didn't know what to do; I tried gently admonishing this young guy and his girlfriend, but walked away wondering if I should have told them to report the person who sold or gave them such a young dog. This was a set-up for disaster, and these kids had absolutely no idea what they were doing. Sadly, I am certain their ignorance was learned: had they been wisely parented themselves, they could not have been so obtuse.

[4] It's exceedingly difficult to translate poetry well—to capture both the sense and the sensibility of it. I was delighted to find that Justin Erik Halldór Smith has met the challenge beautifully with his translation of this Heinrich Heine poem.

Since I first posted this, I have altered the essay in several ways. Most importantly, I had quoted a friend anonymously but without asking her permission, and I have removed the quote. I usually would not have been so careless, but two friends had expressed virtually the same thought, except that one wrote and the other spoke. I therefore quoted the written lines, which the other person could just as well have thought were his, but on principle I should have asked. I am normally punctilious about such issues, and I regret the error. I amended the passage, which in the end led me to reconsider and clarify what I was really trying to say anyway.

Friday, June 24, 2011

Proof you don't need religion (or moral philosophy) to be good

And I say this as someone who thinks a lot about both.  Here is a brief news clip on a remarkable rescue of a dog—by another dog:

Friday, June 10, 2011

Stephen Colbert takes on fracking

Sometimes humor is the best way to make a point.  Many of you have undoubtedly heard of hydraulic fracturing (fracking). Here is Stephen Colbert discussing the process with Governor Tom Ridge, who is currently paid by the oil and gas industry to push fracking in Pennsylvania. It's very short, and very funny (even Gov. Ridge can't help laughing).

Thursday, June 9, 2011

Follow-up on oxytocin and Big Pharma

I really didn't intend to spend so much time/space exploring the netherworld of the pharmaceutical industry, and had planned to move on to matters of beauty, art and books. The subject keeps turning up, however, so I wanted to post a brief follow-up to two items in my "drug series."

1) It turns out that oxytocin is (over)used not just in humans but in .... fruit and vegetable plants. I had mentioned in a previous post the problem of exploding watermelons in China, victims of farmers eager to hasten their ripening for delivery (ahem), but most reports I've seen of oxytocin use in vegetables seem to concern India. See, for example, this article in The India Times. It's hard to square the drug's ready availability to farmers with repeated shortages for human patients, but this just speaks to the complexity of cultural and economic pressures on supply-and-demand relationships for generic drugs.

2) A new article, "Flacking for Big Pharma," has just appeared at The American Scholar. It was written by Harriet Washington, author of the award-winning Medical Apartheid: The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present, and details the corporate takeover of medical journals (and, thus, most of the information that guides physicians in treating their patients). It is well worth reading, especially if you're wondering why the medical establishment seems prone to pirouetting on their recommendations every few years. Anyone remember the big turnaround on HRT (hormone replacement therapy)?  First Premarin and Prempro were hailed for reducing not only the symptoms of menopause but the risk for stroke, heart attack, breast cancer, and cardiovascular disease. A number of years later, further studies not tied financially to the pharmaceutical industry made it abundantly clear that these hormones actually elevated the risks for stroke, heart attack, breast cancer, and cardiovascular disease—the very diseases they had been touted to prevent. 

I'll excerpt a disturbing little tidbit to whet your appetite:
In 2003... Elsevier, the Dutch publisher of both The Lancet and Gray’s Anatomy [the text, not the television show], sullied its pristine reputation by publishing an entire sham medical journal devoted solely to promoting Merck products. Elsevier publishes 2,000 scientific journals and 20,000 book-length works, but its Australasian Journal of Bone and Joint Medicine, which looks just like a medical journal, and was described as such, was not a peer-reviewed medical journal but rather a collection of reprinted articles that Merck paid Elsevier to publish. At least some of the articles were ghostwritten, and all lavished unalloyed praise on Merck drugs, such as its troubled painkiller Vioxx. There was no disclosure of Merck’s sponsorship. Librarian and analyst Jonathan Rochkind found five similar mock journals, also paid for by Merck and touted as genuine. The ersatz journals are still being printed and circulated, according to Rochkind, and 50 more Elsevier journals appear to be Big Pharma advertisements passed off as medical publications. Rochkind’s forensic librarianship has exposed the all-but-inaccessible queen of medical publishing as a high-priced call girl.
Caveat lector.

Saturday, May 28, 2011

You read it here first (or, overcoming climate change avoidance)

I was glad to see that both Climate Progress and Grist are finally drawing attention to the fact that cancer is now the leading cause of death in China.  Perhaps now people will start paying attention to the health consequences of pollution.

I've been pretty flummoxed lately by the abundant attention being given by the press to asthma and respiratory disorders as sequelae of air pollution. Yes, asthma is a problem—it kills eleven people each day in the U.S.—but at least it is treatable and usually controllable, unlike the cancer, birth defects, and neurological diseases arising from toxic pollutants in China (and undoubtedly elsewhere). With all the talk about saving the planet "for our children/grandchildren" and the perils (such as mass migrations and wars over water) that “may” face us “this century” “if we don’t act soon,” I've begun to think that even those of us concerned about the environment have protective mechanisms we're unaware of: without being climate change deniers, we can be climate change
avoiders, preferring to think about the distant impacts of our (in)action rather than the very clear and present dangers we face now, and, indeed, have been facing for decades.

In any case, the Grist article provides more background than my post on the topic
. Though it does hint that the West bears some culpability for the problem (wanting to buy cheap goods made in China), it doesn't go as far as I did (namely, suggesting that our manufacturing plants in Asia are likely polluting the rivers just as much as any other plants there).

Saturday, May 21, 2011

Recommendation: "The Filter Bubble: What the Internet is Hiding from You"

Eli Pariser, of fame, has just come out with a book about how the internet filters information for us—even when we don't know it, and don't want it to. Pariser takes the experience I touched on in The Trouble with Choice, pursues it to its roots, and explains it better than I ever could.

The consequences of this kind of filtering for our political and social life are enormous. Democracy is hard enough when we share the same facts; it is impossible if we are being shunted into parallel universes. 

In March, the TED conference invited him to preview his call for an ethical, open internet. With Bill Gates and Google executives in the audience (!), he made a powerful case: here's a 9-minute video of his talk. It's truly eye-opening.

Pariser's work, interestingly enough, confirms my recent experience of doing internet research for this past week's series on drug shortages.  I found out about the shortages initially through a subscription medical journal, but when I googled to find more widely available reports, I got hardly any useful hits. I found this puzzling, but was even more perplexed when I would perform the same searches again a day later, then the day after that, and so on, and each time get more and more relevant hits that had clearly been there all along. If you've ever noticed this pattern yourself, you've got to watch the video.

And if you haven't noticed this happening, then you really have to watch the video.

Friday, May 20, 2011

Speaking of the connection between human and environmental health...

The Amazonian rainforest 

Frrom the department of perfect timing: as I was finishing the previous post, I received an email alert from an organization called Amazon Watch.  They have a video that is an "open letter" (so to speak) to the citizens of the United States of America from 30,000 Ecuadoran plaintiffs in the recently decided Chevron v. Aguinda environmental lawsuit. Chevron lost the suit but has sworn that they will never pay to remediate the region they have contaminated beyond habitability. Please take a look at the not-quite-three-minute video and sign the letter if you are so moved, as I hope you will be.

Lessons from the shrinking supply & burgeoning demand for vincristine

This is the fifth post in a series on the current drug shortages. I've been interested in peering beneath the surface of the industry reports to look at what this crisis might tell us about how the pharmaceutical industry operates and why our reliance on drugs seems to increase with time. The case of vincristine brings these issues to a head and illustrates why we cannot atomize our societal problems into neat little packages.

Vincristine, one of many drugs currently in scarce supply, is used primarily to treat non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, acute lymphoblastic leukemia, childhood leukemias, and nephroblastoma. Vincristine is derived from the periwinkle plant (Catharanthus roseus), which has long been used in pre-scientific medical practice to treat diabetes and regulate menses. It is now endangered—slash and burn agriculture has decimated its native habitats—but it is widely cultivated. Only two companies produce the drug: Teva says that they have had manufacturing delays, while Hospira says they can't keep up with increased demand. 

A word, then, about increased demand. 

Over the past two decades, the incidence of leukemias and lymphomas, the diseases vincristine treats, has risen dramatically; the rate of non-Hodgkin’s lymphoma alone has doubled [1]. These blood cancers are among the most common malignancies in humans, and the most common in children. Chemicals and agricultural pesticide exposure, hair dyes, and radiation are all well-established risk factors, as are chronic antigenic stimulation and autoimmunity (the incidence of both of which are also on the rise) [2]. The Houston city government’s State of Health report from 2007 offers these shocking statistics: cases of leukemia and lymphoma are twice as high among children living within two miles of the Houston Ship Channel, an area heavily contaminated by petrochemical plants, as those living outside the two-mile radius, and exposure to air pollution in the Ship Channel increases overall cancer risk by a factor of 1000 [3].

The National Cancer Institute states that every hour, an estimated 150 Americans is diagnosed with some form of cancer. That’s one in four Americans.

And we’re not even the ones at greatest risk. Not by a longshot.

A sewage pipe feeding directly into the sea.
In China, 80% of the residents of a small town called Shangba, one of the notorious "cancer villages," have died of some form of malignancy in the past twenty-five years, many in their first few decades of life. Surviving villagers are plagued by kidney stones and skin diseases. Why?  Extraordinary levels of pollution. The village is located near chemical plants whose frequent "accidents" contaminate the rivers that supply water to the town. 

Serious environmental “accidents”— I use quotation marks because somehow the word just doesen't seem to capture the recklessness, greed and sheer stupidity that cause a continual stream of these events—happened, on average, once every three days in China in 2007. In 2009, Dr. Hu Yali, a geneticist at Nanjing University, said he believed environmental pollution was responsible for a tenth of all physical defects in Chinese infants—and birth defects at that point had risen by 40% since 2001. The incidence of neurological and neurodevelopmental disorders is also sky-rocketing. These diseases are not curable. They aren't treatable. And even if the cancers can be treated, it is no use sending people back to live in toxic environments.

It's easier to catch fish when they're already dead.
Needless to say, these diseases are merely the most readily apparent effects of pollution on humans—currently. I suspect that these prevalence and incidence rates are under-reported in China (it would be bad publicity for the totalitarian state), but more to the point, we have neither the ability nor the inclination to track the effects of pollution on animals, wild or domestic. We do know there is a tremendous amount of waste in industrial farming, i.e., unhealthy animals cannot be sold for human consumption—though our standards for what constitutes healthy-enough-to-be-edible are pretty low—but no one does autopsies on most of these animals, and in any case we know that whole species are disappearing around us each day.

If you think that what happens in China is entirely China's problem, think again. Many U.S. pharmaceutical and chemical companies have manufacturing operations in China and India, another country facing dire environmental problems. I cannot help but wonder how many contaminating events involve companies with U.S. ties.

It is one of the bitter ironies of our age that to treat cancer we engage in processes that produce it.

And could contaminated chemicals be contributing to all the "manufacturing difficulties" being reported, along with shortages of plant and animal substrates for the chemical processes?

It's hard to tell, because the drug companies don't specify the nature of their difficulties.  Asymchem Laboratories, a North Carolina-based custom manufacturer of pharmaceutical ingredients with laboratories, pilot plants, and large-scale manufacturing operations in northeastern China, has said that small producers of basic intermediate compounds are disappearing because they cannot meet tougher environmental standards now being promulgated by the Chinese government in response to their enormous health crisis. In their sympathy for small companies, I think Asymchem misses the larger point.

Let's be clear: almost any standard in China would be tough to meet, considering their record. China has been the world’s largest polluter. In the first six months of 2007, the last year for which I could find statistics, the number of environmental accidents increased 98%, along with demand for energy and minerals. It remains cheaper for Chinese plants to employ inefficient processes that waste fuel than to improve manufacturing. (Surely the price of energy is not nearly high enough.) Yet each year, there are articles that repeat the same question asked by this piece from Time Magazine last July:
While the country's [China's] economic boom has always been dogged by environmental and safety hazards, the frequency of disasters this summer has raised new questions about whether the country can maintain its pace of expansion without doing catastrophic harm to its people and the environment.
"Without doing catastrophic harm"? The catastrophes have been occurring regularly for decades. How many years can we witness these disasters and think that they “raise new questions”? How much evidence must accumulate before we stop using “but more studies are needed” as an excuse to keep our head in the sand? The Time article mentions all the outrage expressed over the BP oil rig explosion in the Gulf—but even here in the States, where journalists aren't being jailed for reporting the truth, the consequences of the hemorrhage into the Gulf have dropped off the national radar screen. 

It is worth pointing out the limits of scientific inquiry in assessing damages in situations like these. We have little information on the ecosystems affected by environmental accidents. Before the Exxon Valdez oil spill, for example, there were no baseline data on the abundant species thriving in Prince William Sound. We know some species have disappeared from the area, others are still in very low numbers. But without a baseline, it will always be possible for corporations to argue about the sequelae of an event and debate the numbers. The quest for certainty becomes a distraction.

What does seem certain is that we cannot solve our problems by doing more of the same: using chemicals to counteract other chemicals to counteract others, taking antibiotics to treat the infection we got from eating meat from an animal who itself was given antibiotics.  As treehugger reported just this week, China's watermelons are "exploding like landmines" because the fruit is injected with chemicals to make it grow faster and ripen more quickly. Unsure whether the melons can be safely consumed by humans, they're chopping them up and feeding them to their farm animals.

What's next? A chemical to prevent the explosion of fruit injected with explosion-inducing chemicals?

In philosophy, this is known as infinite regress. 

Industry calls it guaranteed profits. 

Naïveté calls it progress.

Swimming in India

[1] See, for example, Fisher SG and Fisher, RI: The emerging concept of antigen-driven lymphomas: epidemiology and treatment implications, Curr Opin Oncol. 2006 Sep;18(5):417-24.
[2]  Fisher SG and Fisher, RI:The epidemiology of non-Hodgkin's lymphoma, Oncogene 2004 Aug 23;23(38):6524-34.
[4] The Asthma and Allergy Foundation of America; additional statistics here.

Thursday, May 19, 2011

Old treatments, new patents, big money: the case of colchicine

(This is Part 4 of a series examining the current drug shortages and what they might indicate about our approach to health and healthcare. Part 1 described the shortages; part 2 the response of the healthcare industry; part 3 examined one case in which the demand for a drug, oxytocin, seemed to be excessive, and asked how much of our reliance on chemical tinkering actually manifests cultural preoccupations with control over nature and self-improvement.)

The New England Journal of Medicine published a pointed article in 2010 on incentives for drug development. I excerpt it here; if you have access, you can read the full article [1].
In July 2009, the Food and Drug Administration (FDA) officially announced what physicians have long known — that the drug colchicine can effectively treat acute flares of gouty arthritis. The plant from which colchicine is derived was first used as a therapeutic agent for gout more than 3000 years ago in ancient Greece, and the tablet form has been widely available as a generic prescription drug in the United States since the 19th century. On the basis of evidence that had built up over the years, numerous consensus guidelines recommended colchicine as an effective second-line treatment for gout — for example, in patients who had adverse effects from nonsteroidal anti-inflammatory drugs.
It came as a surprise to many patients and physicians that the FDA not only approved the new version of colchicine (Colcrys) but also granted the manufacturer, Philadelphia-based URL Pharma, 3 years of market exclusivity for this ancient drug. The possibility of such an exclusivity period arose because colchicine, despite its longevity, had never been officially approved by the FDA for a particular indication. The 1938 Food, Drug, and Cosmetic Act required that all new drugs be approved by the FDA for safety before being introduced on the market, but it allowed drugs that were already on the market to remain available...
In 2007, URL Pharma organized pharmacokinetic studies testing its version of colchicine in healthy volunteers and a randomized, controlled trial involving 185 patients with acute gout. The combined findings of these studies confirmed the drug's safety and efficacy.... On the basis of this new trial, combined with the previously published evidence, the FDA approved Colcrys for treatment of acute gout. Because this was technically a new indication for the drug, the Waxman–Hatch Act authorized the FDA to award the company 3 years of market exclusivity — an incentive that the agency believes could encourage voluntary compliance with the drug-approval process.
At the same time, under the Orphan Drug Act, the manufacturer also received 7 years of market exclusivity for the use of Colcrys in the treatment of familial Mediterranean fever (FMF), a genetic inflammatory disorder that affects only about 100,000 patients worldwide. The Orphan Drug Act provides federal grant funding and tax credits for clinical trial costs, as well as market exclusivity, to encourage research into rare diseases. The orphan-drug incentive is not restricted to new products: currently available drugs that are approved for a new orphan indication can also be granted exclusivity. For example, thalidomide, a drug designed as an antiemetic agent that fell out of favor in the 1960s after it was linked to birth defects, was approved in 1998 as an orphan product for the treatment of leprosy and in 2006 for the treatment of multiple myeloma. In the case of FMF, the usefulness of colchicine in helping to control debilitating attacks of fever and abdominal pain was already established, and the orphan indication for Colcrys was approved on the basis of a review of previously collected data, along with additional limited safety information from the pharmacokinetic trials.
...After the FDA approved Colcrys, the manufacturer brought a lawsuit seeking to remove any other versions of colchicine from the market and raised the price by a factor of more than 50, from $0.09 per pill to $4.85 per pill. These increased prices directly affect the availability of the drug to patients with gout or FMF who have long been using colchicine safely in an evidence-based manner. Exclusivity can also affect health care delivery more broadly. According to the Centers for Medicare and Medicaid Services, state Medicaid programs filled about 100,000 prescriptions of colchicine in 2007 and paid approximately $1 million for the drug. Use of the new brand-name colchicine could add as much as $50 million per year to these insurance programs' budgets....
Drug companies regularly complain that the costs of R&D are so high they are simply forced to charge more for drugs. There are several problems with this claim. First, many drugs, like colchicine, have been in use for centuries: not a lot of research investment needed in these cases, and no one is offering  patent royalties to native tribes. Second, the vast majority of drugs are “me-too” compounds that differ remarkably little from their predecessors. Again, not much research investment required. Third, the figure bandied about by the industry, a little under $1 billion to develop a new drug, remains vastly inflated even if we limit it to cases in which all the research is undertaken by the company (which is hardly ever the case, since most basic discoveries are made in academic medical centers, where research is funded largely by the NIH). As Marcia Angell, MD, Editor of the New England Journal of Medicine for twenty years, explains
A group of economists—mainly funded by the drug companies—came up with the widely quoted figure on this. They said that it cost $802 million to bring a drug out. They, however, were looking at the most expensive drugs to develop: new chemical compounds developed entirely in house. Most new drugs aren't that at all. Most are what people call "me too" drugs, which are slight variations of older drugs already being sold.
According to these economists, the real cost of bringing out those rare original drugs is actually around $403 million. But they doubled it by factoring in how much money the companies might have earned if they'd invested that $403 million. Moreover, the economists did not figure into their total the many generous tax breaks these companies receive for doing research and development. This is a highly inflated figure.
The fact is that for the last two decades the drug companies have been hugely profitable. Last year there was a little wiggle downward, but in 2002, the 10 biggest American drug companies had a median profit of 17 percent of sales compared to a median of 3 percent for the other Fortune 500 companies. In the 1990's, profits ran between 19 and 25 percent. Prices are high to keep profits high.
Dr. Angell is actually a little off on one point. She implies that drug companies have enjoyed chubby profit margins for only the past two decades or so. In fact, as economist Alek Rozental wrote fifty years ago in “The Strange Ethics of the Ethical Drug Industry” (Harper’s Magazine, May 1960):
Insulation from the cold wind of pure competition is provided by our patent system which actually encourages "limited islands of monopoly." Our laws are, in fact, more lenient than in most industrial countries, especially as they apply to drugs. [...]
Today whether measured as a proportion of sales or of return on invested capital, the net profit after taxes of ethical drug makers are double those of manufacturing as a whole. In 1958, a comparatively poor year, Smith Kline & French netted nearly 17 per cent after taxes, G. D. Searle, over 20 per cent. In the same year American auto makers got less than 4 per cent. The Wall Street Journal commented: "The 1958 performance showed no signs that drug makers were affected by the recession that had other industries stumbling."
The drug industry's favorite defense of its high returns is the fact that it spends more than three times as much on research, in proportion to sales, as does American industry as a whole. But in fact for every pharmaceutical dollar spent on research four are spent on promotion and selling. Moreover, much of this research money goes into "development," which consists chiefly in devising new dosage forms and combinations of ingredients.
So 17-20% in the recession of '58, a median of 17% in the recession of the 2000's: the industry has  consistently enjoyed the same extraordinary profit margins and dominated American industry by the same ratio for over 50 years. Remember this when you hear that it’s not profitable to continue producing drugs once they’re off patent.  And remember colchicine when you’re told that the pharmaceutical industry should not be regulated, because the “free market” and “competition” ensure the best quality for the best price.

Finally, as an addendum to my previous post, which asked whether the availability of a drug didn’t create a need for it as much as the other way around, Prof. Rozental has this to say:
The story of the tranquilizers illustrates the relaxed attitude toward "ethics" of even the most respected firms. To the manufacturers, tranquilizers were much more than an important adjunct in the treatment of severe psychotics in mental hospitals. Sales could be pushed into doctors' offices and into private homes, providing a unique opportunity to reap a harvest. More than half of the $200 million worth of tranquilizers sold annually are bought by normal people who, whatever their inner tensions, lead humdrum useful lives. Reserpine derivatives, based on Indian snake root, are promoted not only for the severely disturbed but also for the "nervous, the tense, the emotionally unstable." Roerig lists twenty-five situations where Atarax is indicated, including apprehension over weddings, depression at funerals, and anxiety over examinations. Meprobamate (under the trade names of Miltown and Equanil) has become a household word and in the space of less than two years fourth among all drugs sold. Smith Kline & French's tranquilizers are said to account for over half of the firm's total profits. No one can deny that tranquilizers have helped the mentally ill and even made it possible to buy commercial insurance against psychiatric ailments.[!] But many of the more potent tranquilizers have dangerous side effects...Others have very debatable therapeutic value or, in the dosage suitable for office patients, are little better than older sedatives at one-twentieth the cost.
In promoting tranquilizers to physicians, one firm spent $100,000 on a single mailing. In elaborate, multi-colored spreads, the industry combines quasi-scientific information with emotional, often subconscious symbols. Atarax ads, for instance, are said to favor blue on the advice of "motivational" specialists. Thorazine for menopausal upsets [!] is illustrated by a heart-rending picture of a woman anxiously watched by her daughter. Doctors are reached by the frequent repetition of "O.K." words such as "synergistic," "potentiating," "sure-fire", and "low toxicity." Little presents are often sent along with the literature and samples.... Wallace Laboratories sent physicians a record with an Oistrakh violin solo on one side and a product plug on the other.
Thorazine, by the way, was and is used to treat schizophrenia and other psychotic states. And you wondered whether  Mad Men was exaggerating the misogyny and manipulation of Madison Avenue....

The next(and final) post of this pharmaceutical series, Part 5, explores a link between the burgeoning demand for a cancer drug, its limited supply, and our environmental problems.

As a treat for having made it through such a lengthy post, check out this page to see Thorazine advertised as a treatment for anxiety, arthritis, asthma, alcoholism, burns, cancer, cancer-phobia, hiccups, ulcers, menopause, busy hospital wards, disturbed patients, nondisturbed patients, former patients, vomiting, radiation sickness, and, yes, schizophrenia.


[1] “Incentives for Drug Development — The Curious Case of Colchicine,” Aaron S. Kesselheim, M.D., J.D., and Daniel H. Solomon, M.D., M.P.H. N Engl J Med 2010; 362:2045-2047June 3, 2010

Our demand for drugs: the case of oxytocin

In the first two posts of this series, I outlined the current prescription drug crisis and the responses of physicians, the managed health sector (PHA) and the pharmaceutical industry (PhRMA). I believe these drug shortages reveal the unsustainability of certain healthcare industry practices as well as fundamental flaws in how we think about health, technology, and progress. To build the foundation for this argument, I will sketch brief case histories of three drugs over the next few posts, beginning here with oxytocin.

The January 2000 British Medical Journal report I referred to in Part 1 of this series noted that in October 1999, the Harvard-affiliated Brigham and Women’s Hospital abruptly found itself unable to procure oxytocin, which it used “in almost every one of its 10,000 annual deliveries.”  Speeding along in my first reading, I suddenly stopped short. Oxytocin was used in nearly every delivery?

As most of you know, oxytocin is administered to induce labor. The hormone actually serves many purposes; all of us produce it naturally, men as well as women, and it has been touted as “the social bonding factor.” It was discovered by accident in 1909 when Sir Henry Dale noticed that pituitary gland extract induced uterine contractions in a pregnant cat; as early as 1911 pituitary extract was being used to stimulate labor [1]. In 1953, oxytocin became the first peptide hormone to be synthesized in a lab. Both Dale, who discovered the hormone, and Vincent de Vigneaud, who synthesized it, went on to win Nobel Prizes.

By 1998, about 16% of labors were induced, by oxytocin, an additional 16% that began naturally were augmented with oxytocin, and the drug was also used post-partum to prevent hemorrhage [1]. Oxytocin use peaked in the late ‘90s and early 2000’s before greater caution set in, as much from an increasing cultural preference in the West for ‘natural’ childbirth as from evidence that exogenous oxytocin could have adverse effects on the infant [2].

The BMJ noted that Brigham and Women’s Hospital did not find that the oxytocin shortage compromised care or the results of labor and delivery. Why, then, was it used in almost every delivery in the Boston hospital? Perhaps self-selection was involved: BWH is a renowned, high-tech hospital that likely draws more women with high-risk pregnancies (or women who are anxious about their pregnancies, or who are technologically inclined). A medical article published in 1999 sheds some light on the attitude of physicians at this time:
In an ideal world, all pregnancies would go to term, and labor would begin spontaneously. In reality, it is often best to deliver the infant before the onset of natural labor... In the past decade, our knowledge of the mechanisms of labor has increased tremendously. In addition, the ability to detect and manage antepartum maternal and fetal complications has greatly improved. As a result, labor can be induced in an increasingly rational and successful manner.
The authors clearly have a strong conception of what an “ideal world” looks like and the kinds of “rational management” that can lead us there. These ideas deserve consideration, but for now, let me just note that last April, a study conducted by Iraqi physicians from 2004 to 2006 concluded that acupuncture largely eliminated the need for oxytocin in women who had undergone ceasarean deliveries [3]. (Persistent shortages of oxytocin had compelled physicians to seek alternatives.)

Along the same lines, a 2004 paper published in Hospital Pharmacy evaluated the results of an antibiotic shortage on patient outcomes and costs and found that the alternative antibiotics they substituted for piperacillin/tazobactam (P/T) reduced the average hospital length of stay by about one day and slightly reduced costs, without adverse effects on patients. This is not to say that drug shortages never have ill effects—they increase the risk of errors, for one thing—but this question has not been formally addressed in most cases. Given that experts consider only about two to four dozen compounds to be the core of our pharmacopia, with the remainder being "me-too" drugs, it is possible that lack of a particular drug poses a problem less because of the drug's unique characteristics than because of the structural consequences of the scarcity (secondary shortages, time spent locating alternatives, etc.).

The oxytocin story does raise other questions, however. How much of our reliance on drugs is necessary, or even beneficial, to our long-term health? And how much does the availability of a drug create our "need" for it? How different is our desire to control events like labor and delivery from our desire to control events like erections? (Have Viagra and Cialis ever been scarce?) And how does the desire for control shade into the wish to enhance abilities like pitching a fast ball, or concentrating in school, or simply feeling happier? Where does treating illness cross over into self-improvement or simply extend our strong cultural tendency to want to dominate nature, subdue our bodies, control our wayward physiology?

The next post will concern the curious case of colchicine.


[2] See, for example, Oscarsson, ME et al., Outcome in obstetric care related to oxytocin use. A population-based study.  Acta Obstet Gynecol Scand. 2006;85(9):1094-8.


Wednesday, May 18, 2011

Supply or Demand?

(This is part 2 of a series on pharmaceutical drug shortages, which began with Not what the doctor ordered. A brief recap: over the past decade we've experienced more numerous and more severe shortages of prescription drugs. Currently over 240 drugs are unavailable, and another 400+ are back-ordered. Roughly half of the unavailable drugs are "sterile injectibles" used for chemotherapy and sedation. Consequences to patients and practitioners abound.)

The web sites of the FDA and the ASHP (American Society of Health-System Pharmacists) list drugs that are in short supply and the reasons for their scarcity. The three general reasons are: “manufacturing difficulties,” “increased demand,” and “no explanation given.” I assume the last arises when a company decides to stop making a low-profit-margin drug but doesn’t want to take the public relations hit that would come from stating the case so baldly.

ow shortages develop: the perspective of managed care organizations

The Premier Healthcare Alliance (PHA) report I mentioned in the
 first post
of this series offers the following reasons for the shortages (the categorization is my own, for the sake of clarity):
Interruptions in supply: “lack of active pharmaceutical ingredients”
Quality control: “Roughly half of the shortages of injectable drugs in 2010 were due to product quality situations such as presence of particulates, microbial contamination, newly identified impurities, and stability changes.”
Consolidation of drug manufacturers (i.e., takeovers and mergers): "Where we used to have two and three [companies] providing drugs in some cases, we now have one.” 
Financial motives, i.e., companies make less profit from generics so they stop making them: "Manufacturers are delaying or discontinuing investments, thereby impacting product availability."
Fear-based financial motives: “Pressures are mounting to offset profit reductions resulting from patent expirations, healthcare reform, and investments related to FDA regulatory compliance for older products." 
The FDA: “The agency requires manufacturers to abide by what are known as good manufacturing processes (GMPs) or else face regulatory action.”
Hm. These last two reasons bear closer examination. It is true that several hugely profitable patents are set to expire in rapid succession, and without new blockbusters in the pipeline the companies are justifiably nervous. But the situation feels dire only because the industry has enjoyed such fat profit margins (at least several times that of the oil industry) for so many decades; the guy with a billion dollars in the bank blanches at the thought of losing a hundred million, but it won't actually make him poor. We should bear this in mind.

Moreover, healthcare reform was actually a boon to the pharmaceutical industry, since it ensured an increase in the number of insured and thus an increase in drug consumption—long-term stability they gladly traded for short-term discounts to insurance—and, astonishingly, guaranteed twelve years of exclusivity rights to branded biologics, far longer than the usual five years given to small molecule drugs. The industry thus maintains its "islands of monopoly" (see discussion in part 4: Old treatments, new patents, big money).

Finally, let's consider the complaint about FDA insisting on Good Manufacturing Practices. How, exactly, are quality controls supposed to contribute to the shortages? Recall that half of the shortages were caused by contamination of one sort or another. I suppose the industry would have preferred to be able to sell the contaminated drugs—at a discount, of course. After all, one aspect of Premier Healthcare Alliance’s mission is to “operate at costs in the lowest quarter of the healthcare system while providing quality in the highest quarter.” Given the subsidized monopolies that healthcare and drug companies enjoy, I assume that ‘quality’ refers to return on investor shares and ‘highest quarter’ means the penthouse suite.

The PHA report elsewhere concedes that safety is a good thing, but then they hedge:

"While the FDA's vigilance of [GMPs] and actions against unapproved drugs help keep medications safe and effective for the public, new regulations may have a downstream impact on the entire marketplace," the report authors said.
I’d say that if the regulations requiring manufacturers to adhere to quality standards didn’t have a “downstream impact on the entire marketplace” there would be no use for them. But you have to give the PHA credit for their subliminal messaging about "new" regulations that "may...impact"; there are no new regulations affecting production that I could unearth, but the phrase conjures an ominous sense of Government Interference looming just around the corner. 

The pharmaceutical industry’s response

Here is the statement issued by the Pharmaceutical Research and Manufacturers of America (PhRMA) in response to PHA’s survey:
"According to the Food and Drug Administration (FDA) and other experts, drug shortages can occur for any number of reasons, including natural disasters; shifts in clinical practices; wholesaler and pharmacy inventory practices; raw material shortages; changes in hospital and pharmacy contractual relationships with suppliers and wholesalers that can cause fluctuations in the availability of certain products; adherence to FDA-mandated distribution protocols, which can impact patients' timely access to medicines; individual company decisions to discontinue specific medicines; and manufacturing challenges," said PhRMA Senior Assistant General Counsel Maya J. Bermingham.
PhRMA has not taken a position on Klobuchar's drug shortage legislation.
The tone of this statement is instructional, as if PhRMA is patiently teaching a class on drug shortages. "Experts say that there are eight reasons for..." It's also slick: you’ve got to admire the way PhRMA doffs its hat to the FDA at the beginning to set up a more convincing accusation later. Unsurprisingly, Big Pharma wants to spread the blame around. First there are the “acts of God”: natural disasters and raw material shortages. Then there are faults with healthcare providers themselves: “shifts in clinical practice,” “inventory practices,” “changes in hospital and pharmacy contractual relationships with suppliers” (a.k.a. drug companies; anyone see any circularity here?). Then, of course, there is the the FDA, which wields the stick of “mandated distribution protocols” (so that hospitals get, say, flu vaccines before retail pharmacies).

To their credit, PhRMA does not complain about having to adhere to the FDA's Good Manufacturing Processes. But notice that they assiduously avoid mentioning their own significant contribution to the problem, industry consolidation. They also fail to cite manufacturing difficulties, which I find curious.

What's missing

The one explanation that is missing from both the PHA report and the PhRMA response is increased demand. It's the elephant in the room no one wants to acknowledge, because it calls into question everything we've been taught to believe about health, technology, the "free market," and progress. I'll take up these implications one by one in the next few posts.