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

Notes:
[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.
[3]  http://www.houstontx.gov/health/HoustonHealth/StateOfHealth2007.pdf
[4] The Asthma and Allergy Foundation of America; additional statistics here.