Recently in Medicine Category

Since March 4th, workers have fished 3,300 5,916 6,601 13,000 (03/18/13) dead, bloated pigs out of a river in Shanghai. Last week there was little information about where they were coming from, how they got there, or what they died from, only general agreement, as Bloomberg put it, that "nothing good comes from a dead-pig tide".

The Huangpu River feeds the drinking water supply for some of the city and although officials have so far assured citizens that the water is safe, and that they're taking water samples regularly, doubts persist.

If Pigs Could Fly

How the pigs got there is still a bit of a mystery. The carcasses are ear-tagged but officials can't decipher the tags, so they don't know the exact situation. Most likely, farmers dumped diseased pigs (some are infected with porcine circovirus) into the river at some upstream province. Despite the gruesome pig panorama, citizens are told not to fear the safety of pigs originating from the suspect provinces.

Piglets
via Wikicommons.

China produces half the world's pigs, five times what the U.S. produces. Pork is so central to the economy that pig price fluctuations effect the cost of living. This means that the large scale pig deaths over the past several months, albeit only tens of thousands in a pig population of millions, concern not only water drinkers and pork consumers but economists too.

When other food products befall catastrophe, the story may be different. When frosts freeze orange groves in Florida, for instance, producers warn consumers in the Northeast U.S. that orange juice prices might go up, that's it. Pig parts, however, are found in hundreds of products besides rinds and bellies and chops and loins. For instance, eighty percent of the U.S. heparin supply comes from pigs raised on farms in China, according to the director of Pharmacy at Boston Children's Hospital.

A few years ago, an epidemic of blue ear pig disease (porcine reproductive and respiratory syndrome virus (PRRSV)) ended up killing so many pigs that producers met the demand for heparin by adulterating the drug with a chemically similar substance. As the crisis unfolded, analysis detected oversulfated chondroitin sulfate that caused hundreds of severe allergic reactions and 175 deaths worldwide.

In the aftermath, journalists investigated the supply chain and found that the FDA had alarmingly little oversight into the production practices on pig farms in China. Since then, the FDA has increased its oversight. However, even last year, the Wall Street Journal reported that the FDA found contaminated heparin from fourteen more Chinese suppliers. The FDA put them on a watchlist with eight others.

They'd Fly Away?

In light of these investigations, consider that pigs provide material for many human life-saving technologies. A recent study describes the possibility of using porcine small intestine patches for pediatric patient cardiovascular reconstruction. Scientists are experimenting with porcine (and bovine) matrices for things like abdominal wall reconstruction.

Although some medicines, like insulin, are no longer made from pigs, the widespread use of pig parts in medicine often goes unacknowledged. Some religions forbid the use of pigs even for medical treatment, and some people get squeamish about pig body parts, according to designer Christien Meinderstsma in this Ted Talk. One Dutch heart valve company wouldn't send her their valve because they didn't want people associating their life-saving technology with pigs.

In her talk on the book, "Pig 05049", Meinderstsma highlights 185 products made with a pig she followed. A Greek cigarette uses pig parts to make a more "healthy", lung-like filter. Some frozen beef steak is made with beef bits glued together with pig fibrinogen or "meat glue". Some collagen injections for facial rejuvenation come from pigs. Pigs are also used to make soap, train brakes, fine bone china, and bullets (not silver, according to the picture...), and more than one hundred other things. They're amazingly ubiquitous, pigs, and floating in China's rivers too.

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Some related posts include Avian Flu In China (2005); Streptococcus suis in China (2005); a note on the heparin adulteration (2008) the H1N1 pandemic - (2009), and here.

Many people muster strong opinions about Oscars - not I. Having enjoyed some of 2012's awarded movies, I watched the Oscars with appreciation, albeit distracted by the din of our crowd. The only thing that always disappoints me, every year, is how many important subjects and films get left out. The 2012 documentary movies "Escape Fire" and "The Waiting Room" focus on healthcare in the U.S.

"Escape Fire"

Escape Fire airs this weekend on CNN. The film isn't shy about its agenda, as one commentator puts it: "We don't have a healthcare system, we have a disease management system." The disease management system in the U.S. comprises many industries - pharmaceutical, insurance, hospital chains, and doctors' groups, so the film covers a lot of ground.

Doctors and patients dependence on pharmaceutical drugs gets shown via an arresting story of a veteran being weaned off of painkillers. The pharmaceutical industry's economic calculations, deadly to patients, are recounted by Dr. Steven Nissen and the familiar story of Avandia. The insurance industry's stake in it all is discussed and memorably captured in a shot of all the insurance company representatives sitting around the table negotiating Obama's healthcare plan. The filmmakers somehow patch together an optimistic if controversial package of solutions for the impenetrable seeming morass they depict. A Safeway executive marshals employees to exercise and lose weight. Media-popular doctors hold forth with various remedies.

The story thread I appreciated most was that of a primary care doctor. To her dismay, time with patients kept being shortened to meet new economic demands. Supervisors told her to "get her productivity up", so she changed jobs more than once, hoping for a position that allowed her to adequately care for her patients.

Aside from patients, primary care physicians have taken the toughest hit in our *efficiency* driven system. There aren't enough of them, and the care in some parts of the country has become so slapdash it's dangerous. Yet at the bottom of every health article, at the end of every pharmaceutical ad, in every news piece about this or that medical research is a bright, incongruous little instruction: "Ask Your Doctor". As if. As if we had the same level of medical intimacy and trust, just technologically superior, as when my great grandfather worked through nights, house to house in his little town.

Interestingly, the system depicted by the riveting film "Escape Fire", however sickly, is what the healthiest patients get, those who have the very best insurance in a places chocked full of excellent hospitals. Fifty million uninsured patients in the U.S. don't get that.

"The Waiting Room"

Which brings us to the excellent film "The Waiting Room", by Steven Nicks, shortlisted in the top 15 Oscar picks. The movie's setting is Oakland, California's Highland Hospital waiting room, over 24 hours. It focuses on a different aspect of the problem than "Escape Fire" and takes a different tone. If on the continuum of polemic reporting, Michael Moore's "Sicko" scored a 9-10, "Escape Fire" might get a 6-7, and "The Waiting Room" would score a 0-1. Healthcare has been ruthlessly politicized in the U.S. and most people will bring some opinion to this film. In turn, the film strives to be empty of politics. It provides details for its characters, but doesn't do voice-overs, doesn't judge, and doesn't demand your defined conclusion.

Deplore the public cost of diverse homeless populations plagued by addictions, unemployment, poverty and in need of medical care? Those people end up at Highland Hospital. Disdain college grads who don't pay for health insurance? They too, sit in this waiting room. Despair a healthcare system that allows people to get sick and sicker until they end up in emergency rooms instead of getting primary care? Those sick people are here. Agonize how social services have been ruthlessly cut in poor cities? Highland Hospital helps these people also.

They sit shoulder to shoulder in our emergency rooms - our institutions of last resort. Every age, gender, and nationality, they're all here, men plagued with chronic labor-related injuries, primly dressed women abruptly out of work, twenty-year olds surprised by tumors, stroke victims who couldn't afford medicine, kidney dialysis patients from other states, and alcohol/drug addicts living on the streets.

But the film doesn't run all their stories together like I just did, in a big forgettable jumble. It follows each person. How did a little girl with tonsillitis end up in the emergency room instead of in primary care? Her parents are separated, but both show up at the hospital. Her dad lost his job and missed his day with her yesterday on account of transportation. He anxiously hops around her during intake. His son died at two. The nurse, half his size, counsels him to settle down so he doesn't scare his daughter. The girl seems numb to it all.

Triage

Whatever you feel about their plight, whatever sentiment or opinion, the frenzied emergency room healthcare system doesn't have time for any of it. Sentimentality? No. Compassion? Yes. Medical technicians and intake nurses and doctors and interns triage when all beds are full and patient tempers are short. They treat patients as best they can, when specialists have months long waiting times, when "non-profit" hospitals turn away poor patients, and when community safety-nets like churches run out of giving.

The outcomes at Highland Hospital can stretch the boundaries of adequate medical care. Fresh gunshot wounds get run into a trauma room, a steady stream of community catastrophes delivered by ambulance, while men with not fresh but unhealed gunshot wounds groan for hours, days, in the waiting room. A homeless man occupies one bed for too long because he has no place to go. Someone who can't get surgery seems pleased with a pain med prescription. This is where the 50 million uninsured people who are not short-changed in the scenes of "Escape Fire" land sometimes enduring hours of wait before they see a doctor.

At discharge, patients summon fragments of pride. They negotiate payments and answering questions about unemployment checks and family resources awkwardly, over a small desk, everyone caught up in unfortunate circumstances. "The Waiting Room" captures the tension of these situations in a refreshingly empathetic way.

If the movie doesn't hammer home a message, it embraces realism. A new doctor, stunned, is told what to say to a family, told exactly which forms of the verb "to die" to use. After one trauma team struggles to save a gunshot wound victim, they attach a tag to a fifteen year old's toe and he gets wheeled into the morgue. We read a small sign next to the refrigerator door: "Put The Body in Any Available Space".

The film, being so good, won't say this, but economically, ethically, and psychically, everything that brought this Oakland boy to that place costs society. Whatever your politics - in every way, it costs you.

Escape Fire and The Waiting Room, two films highly worth seeing.

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The Waiting Room played all over last fall, and aired on PBS. It is now playing a few other places around U.S., and is also available for purchase. The film team also produces an interactive multi-media site.

Today is 25th World AIDS Day, so more people than usual spent time last week reading about the world's progress conquering AIDS. In good news, deaths from AIDS have declined. In Sub-Saharan Africa they have declined by 32% in the last 5 years, continuing an excellent trend. But how do we perceive the progress? We wrote on World AIDS Day, 2009 about how Google tried to correct our search "HIV infections decrease", to "HIV infections increase".

The first search phrase, ending with "decrease", yielded only 1,940,000 results in .22 seconds, whereas the second, ending with "increase", gave 3,550,000 results in .18 seconds.

If Google was tracking a trend, they were wrong, because by 2009 HIV infections had decreased by 15% in 10 years. But we in the world were very accustomed to bad news about HIV infections and AIDS, as Google documented. Today, three years later, there's even better news for HIV/AIDS - on the drug development front, as well as on detection, treatment, and prevention fronts. That was an example in 2009 of how false bad news overwhelmed positive news (via a Google algorithm)

Today, the bad news is that people still die of AIDS all over the world - in Russia, China, Asia, Africa, and the US, where public health officials recently recommended that people ages 15-64 be tested for HIV. African countries, especially in Sub-Saharan countries, still have the most cases of HIV infected people, and many of people aren't being treated for what is basically affordably treatable. But how should we talk about this bad news? That is the subject of this post.

But the Bad News, How Shall We Put It? Shalll We Ignore It?

In the past few years an interesting conflict has arisen about news in Africa. Critics complain that Western media can't take its eyes off the cliched, ailing, and violent aspects of the African continent, thus giving an inaccurate, un-nuanced and harmful view of its many countries. Nicholas Kristof is a popular target.

The group Radi-Aid released a parody video urging Africans to give money to send radiators to Norway ("frostbite kills too"). Produced by Norwegian students, it mocks this so-called "poverty porn" in the style of the 1984 Band-Aid fund raiser. It's a charming video and relays a potent message. But realize that the Radi-Aid video mocks something that's 25 years old - as in, what can't you mock from 1984?

But beside that minor quibble, of course, I see their point, I think anyone can. If you've ever traveled, you've probably run into inaccurate media portrayals of your country that are just crazy. I remember reading an English paper in Asia that had only bizarre stories about the US, things like - Woman in Tennessee Found Herself In Closet Stomping Beetles. What? You had no idea where they found it -- could they have just made it up? Based on American TV shows, little kids would ask me if I ever got shot in a gunfight - NOO?

Cultural misconceptions are legion and universally perpetuated. I'm sure small towns in the Mid-West that occasionally get besieged by floods and tornadoes feel betrayed by the mainstream media too - Hey wait! we have great potlucks here and there's the most amazing other stuff too! New Orleans must have felt that way during and after Katrina. C'mon! Shot after shot of all those people in the stadium? It's not only Africa that's the subject of inaccurate, negative media portrayals, it's every other country, town and borough, and all subjects too - science, math, economics, election polling, women...they all have their bad day via the media and press.

Aid Solicitations, In the Eyes of The Beholder?

For African countries, a lot of so-called poverty-porn starts with international non-governmental organizations (INGOs). INGOs do use sympathy for fund-raising -- large-eyed children dragging teddy bears, or gathered around looking up at the camera pathetically, or forlorn in barren, monochromatic surroundings. To me it gets a little gross, but they use what works, what gets people to reach into their pockets and give money. These images get picked up or pushed upon the media and used as news. Here's a clear example of how deceptive this imagery can be. But these stories don't comprise all the news of any country.

Some commentators have pointed to what they say are "better" portrayals of Africa that could be used to fundraise. In one, a cute kid in a video acts out an Arnold Schwarzenegger movie, interspersed with the movie's gunfight where "2000" people get killed. The video describes him as smart and articulate, without mentioning or questioning as far as I could tell the especially violent part of American culture that the ~5 year old is copying so very, very accurately. So clearly, different people find different solicitations using kids appealing. Some people take offense to a small child holding a bowl up, but have no problem with a small child acting out extreme violence with a pretend gun followed by a plea for donations. Personally, I have as much problem with the second as the first, and would also ask while we're at it -- shouldn't we question the ethics of using a child for fund-raising at all? Or is it ok as long as the child is wearing a shirt and not holding a bowl? (Then there are whole factions of international development that abhor aid altogether and they also have some good points that I'm not going to talk about here.)

Maybe News About Malaria Shouldn't Focus on Africa, Where 90% of All Cases Occur?

To their point, many other countries, India, the US, China, have crushing poverty, but aren't necessarily defined by it, as critics claim Africa is by Western media. That may be true, but when it comes to preventable infectious disease, 99% of people who die from AIDS, malaria, and tuberculosis (TB) live in the developing world, and the center of the HIV/AIDS epidemic is still in sub-Saharan Africa, where 70% of all new infections among adults and 91% of new infections among children occur. Malaria kills about 780,000 people each year, and 90% of malaria cases are in Africa.

Such illness and death devastate families, workers, and economies. When mining companies in South Africa started treating workers for AIDS and malaria, they had a business goal, stop lost productivity. Similarly, in our global economy, Asia's and Africa's problems and successes affect the world. That means that how African nations attend to public health influences our own public health and impacts our companies that invest in Africa.

Reporting on Africa is not just about Africa, it's about us in the West too. Reporting is not a selfless endeavor. We absolutely should be reporting on Africa's "bad" news (not exclusively of course). Our public health problems (e.g. infectious disease, antibiotic resistance) derive from and are dependent on not only our own public health systems, but also those of developing nations. Our health depends on the policies, laws and regulations all nations produce and uphold for preventing and treating disease, and for drugs and pharmaceutical companies.

Progress of International Development

For close to a century, international development has sought to raise basic standard of living the world over, not just Africa, but South America, Asia, Central America and parts of North America. Driven by various agendas and business interests and research, we've compiled a long history of what has worked and not worked. For many reasons, what seemed to work in Asia, South America, Central America, etc. didn't work well in Africa. In addition, various national tragedies bogged down progress there. No sooner was apartheid defeated in South Africa, for instance, then AIDS struck. Journalists weren't wrong to cover these events.

Journalists reporting these stories have also sometimes brought needed attention that often benefits the subjects. For instance media outlets reported on the 39 pharmaceutical countries that sued South Africa when it tried to import affordable AIDS drugs at the height of the AIDS epidemic. The companies eventually dropped the suit. When President Mbeki refused to acknowledge that HIV caused AIDS, the media was there. The media now has more opportunity to report positive AIDS news.

Prosperity To Spare

Recent prosperity in the west gave people the means to donate money and ideas for aid organizations. Take the Gates Foundation, founded in 1994. This 2001 Seattle Post Intelligencer article writes about how Bill Gates started slowly learning about international development and health needs in 1998:

"I had no idea," the Microsoft co-founder said. "I learned a lot about the whole vaccine miracle, about how effective they are and yet millions were still dying from these diseases.

"So we decided, jeez, the impact we could have by getting vaccines to these children and getting more funding for research into new vaccines could be just incredible."

That was only about fifteen years ago. A world business leader "had no idea" about preventable diseases in Africa. It's easy not to realize how many advances have been made in the past few decades, in part because what was unheard of in 2000 has now became common knowledge to everyone. Globalization of business has brought increasing attention to development issues that are no longer "a world away". But make not mistake, most of these ideas have been around for decades, like the fact that women's education is key to development. Vaccines have long been (albeit controversially) considered the ideal solution to diseases.

What's new is that foundations like the Gates Foundation are increasingly media savvy, and the media is increasingly in tune with the goals of development. This environment made it possible for Kristof to start writing what he did, and in many ways his articles were in synch with US development goals and rhetoric. (Part of the rational for invading Afghanistan, for instance was women's education.) But many of the most popular articles, for instance Kristof's, also opened readers' eyes to both positive as well as alarming stories outside of their mostly elite, privileged self-indulgent New York Times world view. Not a bad thing. Increasingly, global connections have eased people's ability to travel to different countries, increased curiosity about different cultures, and along with that, encouraged inclinations to want to help (I'm not going to argue whether the burgeoning aid industry is good or bad, but some of the 'wanting to help' inclinations, are selfless).

So Does Media Portray Africa Too Negatively?

A recent BBC program asked the question at a conference in Kampala, Uganda: Is media propagating negative stereotypes of Africa? The opinions were very interesting, ranging from a couple of people who that said African leaders themselves inflate problems in order to get foreign aid, to those who said that Africa was seen not as a problem but as an investment opportunity for many countries.

Of course there should be positive stories about African countries. But don't ignore the good that comes publicizing problems. While South Africa struggled with its AIDS crisis with the world advocating for its citizens, countries like China for years suppressed news of its AIDS epidemic. Other alternatives exist also, reporters and columnists who ignore and glaze over tragedy, and focus only on business that privileges the elite, and ignore those who are not in the elite. You can find those stories anywhere, if you would prefer them.

A few years ago, the FDA mandated tobacco companies put the labels on cigarette boxes warning smokers about the deadly health effects of tobacco. The tobacco companies sued, claiming the FDA was "compelling speech", which was unconstitutional. Last year we checked in with the legal wranglings of the case when one District Court judge ruled that the tobacco companies shouldn't have to display the images or print 1-800-QUIT-NOW on cigarette boxes.

Cigarette Warnings
via the Food and Drug Administration.

The battle over graphic picture tobacco warning labels is actually world-wide and decades old. Tobacco companies fought ferociously against the first country that tried to enforce graphic labels in 1986, fashion-forward Iceland. Today, more over 50 countries require text warnings, and a growing number are moving to picture warnings. Australia passed one of the strictest laws, as Stanton Glantz recently described:

"All the cigarette packages are going to have to be the same kind of puke-green color with the name of the company and the variety on standard type on half the pack, and the other half of the pack will be a large graphic warning label."

Graphic Labels: Nails in The Coffin?

The cigarette companies battle against these labels for a reason. Compared to text warnings, the graphic pictures scare the heck out of smokers research shows, especially people with less education.

However, through the court systems, tobacco companies have successfully bogged down governments' attempts at regulation. In Canada, the Supreme Court last year ruled that Imperial Tobacco couldn't draw the government into a class action case. Imperial had argued that the government shared the health costs of smoking since it had allowed Imperial to market "light" cigarettes. The court dismissed their argument. In Scotland, Imperial Tobacco recently challenged the government ban on displays in shops, claiming that the law is "anti-choice". Scotland's' Supreme Court - Lord Hope, Lord Walker, Lady Hale, Lord Kerr and Lord Sumption, are currently hearing arguments in the case.

In the US, tobacco companies recently asked the Supreme Court to hear their First Amendment arguments after another District Court claimed that the FDA rules were constitutional, the opposite of the previous District Court's decision. The tobacco companies have petitioned the court to decide 1) whether the FDA's label mandate violates the First Amendment 2) if the FDA is stepping on companies' free speech rights to promote "modified risk" products, and 3) whether the companies have a First Amendment right to offer free gifts and samples to entice potential smokers. The FDA has until the end of November to respond, and after that the Supreme Court will decide whether to take the case.

Tobacco: A Dilemma?

Some observers speculate whether the Supreme Court will take the case, but authors of a recent New England Journal of Medicine article think the Supreme Court will hear it. The NEJM article reviews the background of the commercial speech doctrine and the speculates various outcomes for the case.¹ The authors say commercial speech was first recognized as a lower value speech in the mid-1970's. From there, the court has enabled creep that brings the commercial speech doctrine to its current very controversial status, where it can essentially curb states' abilities to candidly warn consumers about about health risks of things like smoking.

Because of the court's commercial speech doctrine, the authors write, the FDA can best frame their arguments for the cigarette warnings as promoting consumer choice, rather than as protecting public health and discouraging smoking. This not only hobbles the FDA's ability to frame and defend their arguments for public health, the authors write, it gives the cigarette companies the advantage in defending themselves because they can argue that the FDA is not trying to promote consumer choice, rather it's attempting to influence the behavior of smokers by browbeating them.

Faced with the science related to tobacco, the health affects of smoking, and the tax burden of health costs shared by all citizens, tobacco's costly legal protests seem crazy. However, the Supreme Court has often sided with corporations, and has been quite skeptical of government regulation. As well, science and economics don't necessarily win the day over "free speech" in US courts. So altogether the FDA's idea that science derived photos inform consumers in ways that are hard to ignore, these arguments may not win. The Supreme Court hasn't seemed particularly swayed by science arguments or sympathetic to public health arguments.

So if the tobacco companies and courts continue to dither over the FDA's graphic warnings, thereby keeping them off the cigarette boxes, maybe journalists can write lots of stories about the controversy and include lots of the graphics that the smokers are missing out on?

¹Ronald Bayer, Ph.D., Lawrence Gostin, J.D., and Daniel Marcus-Toll, M.S.: Repackaging Cigarettes -- Will the Courts Thwart the FDA? November 14, 2012DOI: 10.1056/NEJMp1211522

A malaria vaccine over two decades in the making given to infants in Africa was shown by preliminary data to be 30% effective. Good news or bad news?

It depends on who you talk to. Most scientists and public health workers described the partial phase III clinical trial result of RTS,S/AS01 as disappointing, frustrating, or underwhelming, while trial sponsors, a few scientists, the government of Ghana, and KTN streaming LIVE from Kenya 24/7, remained upbeat, stressing that given the millions of malaria infections, a 30% reduction in would give the vaccine a significant place in malaria prevention.

In 2010 there were an estimated 216 million cases of malaria and 655,000 deaths, 91% of which were in Africa. In the past decade years, the concerted effort to combat malaria has decreased deaths and infections significantly, by 25%. But without a doubt, an effective malaria vaccine would be, if not the end of a horrible scourge, at least be an excellent addition to the arsenal of indoor spraying, bednets, and available treatment options. The question is, given the costs of developing and deploying a vaccine and the current economic climate, what's considered effective?

Rough Waters
via Creative Commons License.

This month's 31% results are disappointing compared to last year's results from older kids, 5-17 months, that showed the vaccine to be 55% effective. As well, the newest results from the Phase III trial, show about half the efficacy of those from the previous Phase II trial for the same-aged infants, which seemed to show the vaccine as 62% protective.

Not 55% but 30% Effective

The RTS,S vaccine targets the Plasmodium falciparum and is made with proteins from both the parasite and Hepatitis B virus that serves to enhance the immune response. So why is the vaccine now apparently only 31% effective at preventing infection and 37% effective at preventing severe disease, almost half what it was? Scientists have several hypotheses. It might be the high levels of malaria around the test centers included in this data release, or that increased immunity from mothers in the younger infants blunts the response of the infants' immune systems against the vaccine, or perhaps since the vaccine for the infants was administered with other vaccines the infant immune systems responded less vigorously to the malaria shot. What there's no question about is how tricky it is to make a vaccine that successfully combats infection from an evolving and evasive parasite that moves through different stages of its lifecycle in different parts of the human (host) body.

With the efficacy data so low, scientists were left emphasizing how safe the vaccine is (important, of course, but not exactly the point at this stage). They stress how successful of the logistically complicated and ambitious trial (across 11 centers in 7 countries). Indeed the trial logistics are impressive, important, and a huge inroad to drug testing and public health, but the accomplishment doesn't address the high expectations and promises made during last year's data release.

Glass Now Less Than Half-Full

While the results were discouraging, some scientists weren't surprised. When researchers announced last year's interim results some scientists predicted based on the data that the younger 6-12 week cohort would be less protected by this vaccine. This was one of several caveats scientists pointed out. They also warned against early incomplete data releases, stressed that the older children weren't the target group, and questioned various aspects of the 55% number. We covered some of these questions in a post -- the same caveats and questions apply to this year's data release.

Vaccine development, especially against malaria, is incredibly difficult. Although there are about 30 vaccines in development now, according to the World Health Organization's Rainbow Tables, the closest candidates are 5-10 years behind this one. This fact of course influences the biggest unanswered question: How effective does a vaccine need to be in order to be put into production? There are limits to both attention and money available for urgent public health initiatives, so realistically, funding one initiative can potentially handicap others - but then the argument always swings back -- there is no malaria vaccine right now.

Vaccine Goals - Made To Be Eschewed?

To help guide answers to this question, the World Health Organization, in concert with invested organizations including the public and private sponsors of this vaccine, established in a roadmap(pdf) a "Strategic Goal" to "by 2025, develop and license a malaria vaccine that has a protective efficacy of more than 80% against clinical disease and lasts longer than four years." RTS,S/ASO1 is no where near this. But the WHO also established a "Landmark" Goal, to "by 2015, develop and license a first-generation malaria vaccine that has a protective efficacy of more than 50% against severe disease and death and lasts longer than one year." WHO is currently in the process of updating the roadmap, but warns that the Landmark goal is not being changed.

All scientists acknowledge that only more data analysis from this trial will provide clearer answers. The WHO provides information on vaccine development and its role in assessing the vaccine in 2014-2015. Some scientists predict that the trend of decreasing efficacy after 6 months shown in the data looks ominous: "The results look bad now, but they will probably be worse later", said vaccine expert, researcher for competing vaccines, and deliverer of not-very-upbeat messages Adrian Hill of Oxford University. (But if subsequent data looked somewhat better - the situation of this year's results compared to last year's - the reaction would probably be euphoric.)

Last year when we discussed the vaccine we commented on possible later outcomes that could stem from the incredible hype around interim results releases -

"...which leads us to wonder whether mid-trial fanfare primes us react to whatever future malaria vaccine news comes along with knee-jerk positive determinism? What if the younger data shows only (say, hypothetically) 30% efficacy? Would we ever abandon the effort...?"

Commenting on the latest results, Andrew Witty, GSK CEO told reporters in a conference call "We've been at this for 30 years, and we're certainly not going to give up now".

In other malaria vaccine news Sanaria, another malaria vaccine maker whose founders have been knee-deep in malaria vaccines for decades, recently hosted 7th graders in an event hosted by Montgomery County universities. The idea was to introduce kids to science and medicine so they don't think of people who work in biosciences as "crazy scientists", said Stephen L. Hoffman, founder and CEO of the company. Hoffman's latest malaria vaccine effort was profiled by Science in "New Hope for Crazy Vaccine", briefed by us last year. Sanaria received $3 million funding for Phase II trials last summer.

In still more malaria news, a program called the Affordable Medicines Facility - Malaria(AMFm) has been radically downsized, killed, and folded into obscurity within the Global Fund. The reasons remain a little mysterious. By all accounts, the program was successful, even "overwhelmingly successful", in lowering the pharmacy prices of drugs called Artemesin Combination Therapies (ACTs). If you contract malaria in Africa you often need to buy your own drugs. Patients will naturally buy the cheapest drugs, which happen to be those that are least effective or most susceptible to antibiotic resistance. The program made the ACTs competitively priced with monotherapies, therefore competitive in the marketplace and helpful to preventing artemisinin resistance and conquering malaria. The strategy was innovative and effective.

However, some critics claimed that this method wasn't getting the drugs to children, and that some people were buying up the drugs without a diagnosis. Defendants said these criticisms moved the goal posts, phase II could have solved some problems. But more scientists aren't at all sure why the program got cut, some suggesting that for some reason Oxfam and the President's Malaria Initiative lobbied hard against it. One contingent that is probably pleased with the outcome has been lobbying vigorously against AMF-m since its inception. The group's members are variously affiliated with pharmaceutical companies, 'free enterprise think-tanks', and target lobby efforts like "Africa Fighting Malaria", they selflessly devote their lives to promoting DDT spraying, and lobbying against generic drugs. One or more have written accounts claiming that the competitive pricing schemes employed by AMF-m used cheaper drug suppliers with inferior services -- a spurious, tedious and surprisingly effective go-to argument for decades by pharmaceutical companies lobbying against generics for the most deadly diseases AIDS, Malaria, etc.

A US Court blocked the FDA from requiring cigarette warnings on boxes this week, calling the graphics "emotion-provoking images...". U.S. District Judge Richard Leon decided in a Washington court yesterday that tobacco companies shouldn't have to display images of diseased lungs or a cadaver bearing chest staples on an autopsy table, because this would "unconstitutionally compel speech." Nor should companies have to print 1-800-QUIT on cigarette boxes.

I guess what he's saying is that cigarette companies have the right to package fantasies up in the tobacco they manufacture, fantasies of how cool smokers are, that blithely omit the disease and death their product metes out. The FDA, on the other hand, has no right to present the more accurate side of the story.

You know that smoking causes cancer, heart disease, vascular problems. Did you know that smokers have 7 times the risk of abdominal aortic aneurism (AAA) than non-smokers? You probably know about second-hand smoke. Did you know about third hand smoke which stays in home and hotel walls and ceiling tiles for 30 or 40 years, affecting the health of not only present but future occupants?

The judge says the images on cigarette boxes crossed the line between "factual information" and "government advocacy". The line is "frustratingly blurry", he says, but he sees it.

Does International Public Health News Compel Us to Cheer Enthusiastically?

Everyone wants drugs to cure diseases. Everyone wants vaccines to prevent them. And in a world of urgent international public health problems, what is more publicly urgent then developing solutions for AIDS or malaria? Positive news on this front is always welcome, and in line with that, you don't win popularity points by sticking pins in up-beat public health reports, results, or clinical trial data. Popular science journalists generally talk about cool, politically neutral science, or slick technology, or brilliant research successfully advanced to save lives; they write about winning clinical trials that will end scourges, any scourge - cancer, AIDS, Hepatitis, obesity... Good news!

Cheerful news, like recent headlines highlighting research showing a vaccine for malaria that may be 55.1% effective. NPR headlines enthused "Vaccine Slashes Infection Risk By Half", whereas a more cautions USA Today said: "Malaria Vaccine May Have Potential to Save Millions".

The RTS,S/AS01 vaccine is a decades long effort, now a collaboration between The Gates Foundation funded PATH Malaria Vaccine Inititive (MVI) and GlaxoSmithKline (GSK). The partners recently published interim results in the New England Journal of Medicine (NEJM)² and presented their results to the media. By all accounts, the Phase III trials delivered very good news.

The Mosquito Drawing by M. R. Villarreal can be found at Wikipedia ¹

But What Does "May" Mean, in "May Save Millions"?

No one could say that Bill and Melinda Gates haven't changed the face of international public health. Mr. Gates leads a relentless campaign pushing the power of vaccines; he berates governments that don't vaccinate enough people; and he effectively leverages the media to deliver his messages. Last year the Gates Foundation held a fund-raiser hoping to collect $3.7 billion from governments and instead received $4.3 billion. As Global Alliance for Vaccination & Immunization's (GAVI) chief executive put it, "Bill was a little like a poker player who put a lot of chips on the table and scared everyone else off." Perhaps Gates is more a bridge guy, but point taken.

Given this, who would write-up the newest Gates Foundation news as, "a vaccine shown to be at best 44.9% ineffective in a half-done clinical trial"? No one. With the intense drive for upbeat news, I credit USA Today for their cautious "may save millions". But if you look more closely, for instance read the editorial accompanying the NEJM report³, or listen to scientists around the web and in journals like The Lancet ⁴, or pay attention the malaria researchers interviewed by "Nature News⁵, the caveats of this recent malaria study grab your attention:

1. First, there's the announcement itself. The data released is interim data; the full results of the malaria trial will be released in three years. Interim data releases are not unprecedented but past experiences, for instance with an AIDS vaccine, caution us against overly enthusiastic receptions for incomplete trials.
2. The interim results were reported for children aged 5-17 months, but the target age group is infants aged 6-12 weeks. In other words, these results don't address efficacy of the vaccine for the target group.
3. NEJM reported that at 12 months, the vaccine reduced episodes of malaria by 55.1%. However a US military scientist working with Sanaria, a competing vaccine maker, told Nature News that RTS,S actually offered only 35-36% protection 12 months after the vaccine. It appears that the efficacy of the vaccine might wane over time.
4. Although the reports noted reduced mortality, another scientist emphasized to Nature News that the data didn't support that announcement. Scientists hypothesize that the vaccine may just delay infection.
5. Although the vaccine reportedly cut severe disease in older kids by 47%, combining that data with the available data of the younger kids gave only a 34.8% decrease. This suggests the data for the target group of younger kids might turn out lower than reported in these interim results.
6. In addition, incidents like convulsions and meningitis might be more frequent in the vaccinated group.

These might not be showstoppers. For instance researchers hope that booster shots will improve efficacy. But what if in the end the much touted vaccine turns out not to be a vaccine but just another shot? Scientists and public health workers concern themselves with such non-trivial caveats. What's behind the apparently waning efficacy? How is the adjuvant effecting immunity? Science is exacting even when media reports are not. People also have underlying concerns about what's driving policy, science or the press releases?

Is Marginal Progress, "Success"?

Two of the people interviewed by Nature News are affiliated with Sanaria, a company that is also developing a malaria vaccine. Sanaria just released their own news of a Phase I malaria vaccine study testing the safety of a live attenuated virus. Nature interviewed the first author on the Sanaria study published by Science, as well as the CEO and last author on the Science study. They were complementary of the RTS,S effort, if somewhat critical on some points.⁶

It's worth noting the history of the Sanaria vaccine, to give context to the executives' comments and perspective. Like the RTS,S vaccine, Sanaria's vaccine is an extremely expensive, tricky, and laborious endeavor. The underlying idea for seems promising, but for starters technicians must painstakingly dissect out the salivary glands of mosquitoes in order to develop the vaccine.⁷ It's unclear how this can scale.

On top of the laboriousness of vaccine development, once the vaccine was made it didn't seem to work. In their first clinical trial, Sanaria injected 44 subjects. 42 people got malaria and 2 didn't, a 4.5% "success" rate. These subjects might have been better protected from malaria lounging in a malaria endemic region in mosquito-infested huts, but the Sanaria execs quickly pointed out that it wasn't the stunning failure it looked like, rather, it was a trial that "yielded positive results" -- as their press release put it (without including relevant numbers). The company is buoyed by such "success" and primed for the next controversial⁷ phase.

Because vaccines promise a silver bullet solution to disease, at the moment, every possible vaccine holds promise, since we have no viable one.

Sanaria's position as competitors doesn't invalidate their commentary on RTS,S (complementary as well as critical), since Sanaria executives voiced reservations shared by many others. An editorial in last week's "The Lancet indicated that the release of unorthodox partial results seemed to be more politically than scientifically driven. Diplomatically, The Lancet editors wrote: "although the latest findings are encouraging, we look forward to the full results of the RTS,S/AS01 trial in 3 years time."⁵

When There is No Treatment, What Does A More Effective "Treatment" Look Like?

Will the upcoming younger cohort data meet World Health Organization (WHO) goals of 'Protective efficacy of more than 50% against severe disease and death lasting longer than one year'? ⁵ This is an important question. Vaccine experts usually aim for 80% or more efficacy, and representatives for PATH say they hope to get there eventually. So then, does that make this vaccine a beta version?

Is all this media hoopla deserved for a beta version vaccine? A physician working in Africa distributing bed-nets warned against statements that might mislead people "to overestimate the impact of any single new intervention", in a comment at NEJM. Acknowledging this commenter also has vested interests doesn't detract from his message. 75% of the MVI/GSK study participants used bed-nets. But would people in real-life discontinue the more cumbersome bed-net efforts with a vaccine on the horizon? Will bed-nets still be funded with a 50% effective vaccine? A 30% effective vaccine? If you're a mom and your kid gets a vaccine that is 50% effective, what precautions do you then take to prevent infection? Does a 50-50 vaccine make your life better?

The tremendous investment in vaccines, both in terms of money and expectations, shouldn't slow other prevention and treatment efforts. But realistically, we don't have unlimited resources. It would be naive to think that the prolonged difficulty of vaccine development, the immense investment, and lack of a viable alternative don't influence funding and policy decisions.

Some of the problems scientists identified with this vaccine trial have persisted for years. In this 2006 book chapter recently released online, an economist analyzes RTS,S vaccine data of previous trials (PDF) (HT Nature News⁵). He reports on waning efficacy; and questions how the public health community decides which vaccine candidates merit further investment. 5 years later, as the latest trial barely noses over the 50% bar, we grapple with the same issues and questions he raised back then, but billions more dollars have been invested.

Which leads us to wonder whether mid-trial fanfare primes us react to whatever future malaria vaccine news comes along with knee-jerk positive determinism? What if the younger data shows only (say, hypothetically) 30% efficacy? Would we ever abandon the effort? As more and more money gets invested, do decision makers begin to act less rationally?

Media reports may boost stocks, may raise money and may discourage competitors, but in the end, the science behind the vaccine, the science that's supposed to underpin public health decisions, is fussy and complicated -- caveats matter. After all, you're asking people and governments to donate tens of billions of dollars, and you're promising 7 billion people that your vaccine will keep millions safe.

Tough Economy for an IPO?

Can we push for an end to malaria as if we were trying to put a computer on every desktop? Does this big money, big marketing, big media approach to public health that some find so jarring actually work? I'm not saying it doesn't. Perhaps it will become a more accepted way of developing medicines and vaccines. Maybe public health needs exactly this kind of paradigm shift.

But even if a 40% or 50% effective vaccine is acceptable from a public health perspective, once this vaccine is developed, governments will still need to consider costs. In this economy, some ask, how much will governments shell out for a vaccine with a 50% efficacy rate? Can you and should we market vaccine with lots of pre-release fanfare to push governments towards buying the vaccine?

Asked about cost per vaccine, GSK wouldn't answer directly, but stressed how the company will reinvest all the proceeds to improve the vaccine. Shares of GSK rose slightly on the RTS,S vaccine news, and shares of biotech company Agenus which makes the RTS,S vaccine adjuvant rose from $.48 prior to the announcement, to $2.80 (which got Agenus re-listed by the SEC). All things that may influence decisions. However when questioned about the unconventional data release, PATH's MVI director didn't mention politics, billions of invested dollars, stakeholder expectations, or the saved Massachusetts biotech companies. He said: "we felt it was our scientific and ethical duty to make the results public when they become available."⁵

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¹ The mosquito drawing is by Mariana Ruiz Villarreal. It is the anatomy of a Culex pipiens, a vector for malaria. This image was selected as Wikipedia's Picture of The Day for 10 September 2010.

³White, N. F.R.S.; A Vaccine for Malaria October 18, 2011 10.1056/NEJMe1111777

⁴Editorial: The Lancet, Volume 378, Issue 9802, Page 1528, 29 October 2011, doi:10.1016/S0140-6736(11)61659-0

⁵Butler, D.; Malaria Vaccine Results Face Scrutiny: Published online 26 October 2011, Nature 478, 439-440 2011, doi:10.1038/478439a

⁶Epstein et al: "Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity": September 8 2011 Science 28 October 2011: Vol. 334 no. 6055 pp. 475-480 DOI: 10.1126/science.1211548

⁷ Kappe1, S., and Mikolajczak1, S.; "Another Shot at a Malaria Vaccine". Science 28 October 2011: Vol. 334 no. 6055 pp. 460-461 DOI: 10.1126/science.1213934

⁸ Farlow, Andrew.; "A Review of Malaria Vaccine Candidate RTS,S/AS02A", Chapter Three of The Science, Economics, and Politics of Malaria Vaccine Policy, a report written in 2005 and 2006 and published 14 April 2006 and January 2010. Department of Economics, and Oriel College, University of Oxford.

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We previously wrote about Phase II Clinical Trials of the RTS,S vaccine here. We wrote about US funding for malaria here and here; vaccine strategy here; malaria prevention here and here. We've also written frequently on international public health, including the development of a AIDS vaccine, here and here.

The Map

Acronym Required previously wrote about parents who self-vaccinate in lieu of getting vaccinations, a sort of barbaric hazing for this era's unlucky children. And while some people in the West shun vaccines because they think they're dangerous, people in Africa shun them because they suspect shots are a Western plot to kill them. The US shockingly fanned the flames of the vaccine avoidance trend when it faked a vaccine campaign in Pakistan in order to to get access to Osama bin Laden. Meanwhile, tragically, people continue to die because there aren't enough vaccines to protect them.

When people refuse vaccinations, we lose herd immunity; microbes have get a chance to mutate; and of course people get sick and die. The trend has contributed to large outbreaks of whooping cough, mumps, chicken pox, and measles world-wide, as well as polio, typhoid fever, meningitis and hepatitis A. Now there's a great map Vaccine-Preventable Outbreaks, put out by the Council on Foreign Affairs, so you can see the impact of this all.

(The vaccination map ranks as one of my favorite maps, as does Newspaper Map.¹)

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¹ Granted the UI's sometimes not entirely there

We previously discussed vaccinations in Maher's Mainstream Media Anti-Vaccination Campaign; The Wild Wooly Internet; Polio Vaccines, The End of a Scourge?; Vaccine Development For Developing Countries and others.

It's a well known strategy they say. But how well known is it if the world's biggest encyclopedia doesn't even have an entry? Anyway, it goes like this. Say you're the owner of a dog who's just bitten someone. If you're a chuff, churl or cretin -- or even your average defensive citizen -- you deny it via the so called "Four Dog Defense". Here's how one lawyer explained it to the St. Petersburg Times in 1997 ¹:

1. First of all, I don't have a dog.
2. And if I had a dog, it doesn't bite.
3. And if I had a dog and it did bite, then it didn't bite you.
4. And if I had a dog and it did bite, and it bit you, then you provoked the dog."

The St. Petersburg Times article wasn't actually about a dog, but about the landmark tobacco cases. And the tobacco industry played it something like this, as you may know (I'm ad-libbing here):

1. Smoking definitely doesn't cause cancer, there's no evidence it causes cancer.
2. There's no consensus on the evidence; smoking may cause cancer but second hand smoke definitely doesn't.
3. Mice may get cancer but mice are not humans, cigarettes are not additive.
4. People choose to smoke -- and who are we to impose on people's constitutional rights? - etc.

Four Dogs Launched a Thousand Ways

"Four Dog Defense" might sound more like a Kung Fu movie to you, but since you've now been introduced, you'll see it often. Some people describe the Four Dog Defense as a trial lawyer's adage, but it's even more common than that. The tobacco industry, as in the above example, used it for decades to successfully deflect charges that cigarettes cause cancer. Even today, despite volumes of documents in the form of the tobacco papers, the same companies today mount the same defense.

You might also be familiar with this strategy not only because of tobacco, but asbestos, lead, arsenic, or any number of chemicals or "benign" products (sugar, alcohol, etc.) currently on the market.

The Natural Resources Defense Council (NRDC) used the example of the "Four Dog Defense" to frame their recent investigation: "The Delay Game: How the Chemical Industry Ducks Regulation of the Most Toxic Substances". The report compellingly describes tactics the industries used to stall regulation,focusing on three chemicals, trichloroethylene (TCE), formaldehyde, and styrene. The three have been on the market for decades despite proof they cause morbidity and mortality.

The NRDC describes how vested industries spent millions of dollars stalling with tactics like demands on the EPA conduct new science reviews. Industries request "independent" assessments and hire "independent" scientists to do favorable studies. They then dispatch lobbyists to "influence" politicians and the EPA. Thus, toxic chemicals like formaldehyde, lead, atrazine, and TCE can stay on the market for however long it takes to do the "new" assessment, as the EPA gets stalled from acting on well established science.

Of course taxpayers pay for all of this, every move that industry makes to stall the EPA - demanding studies, suing, producing biased studies, and publicizing contrarian views.Circularly and ironically, taxpayers who already paid for the research trying to assure that we live in a healthy environment, then pay for defense when industry and lobbyists attack that very science. The taxpayers pay and pay again with money and health, for these attacks on science and the EPA (that the Tea Party and GOP so dearly want to abolish).

The TCE Story

This four dog defense strategy has kept trichloroethylene (TCE) on the market for decades. TCE is a solvent used for metal degreasing. It has industrial uses, like cleaning airplane parts, but is also found in household items such as paint removers, glues, correction fluid, electronic equipment cleaners, rug cleaners, and adhesives. TCE is linked with leukemia, cancers, developmental defects, and problems with the male reproductive system, the immune system, liver, kidney and nervous systems.

TCE is also found in hundreds of Super Fund sites, places like like Lawrence Livermore National Laboratory and military bases. Most of us live close to one of these sites, or we might. When a new housing development gets built in the vicinity of some high stature physics lab in an expensive suburb, for instance, TCE can leach from the soil into water supplies, or evaporate into the air. And then what happens if a homeowner or their children get sick? The four dog defense continues. The effects of TCE on human health were detailed in Jonathan Harr's 1996 non-fiction book A Civil Action.

A Civil Action

As Harr recounted, in the late 1970's people began to die in Woburn, Massachusetts, in what public health officials identified as a leukemia cluster. Three companies, including W.R. Grace and a tannery owned by Beatrice Foods, dumped TCE onto land and it leached into the water supply. During discovery before the trial, companies' defense lawyers deposed the plaintiffs, grilling them on the details of their daily lives. As Harr describes in his book, the lawyers produced exhaustive inventories of products used in each plaintiff's house, what they ate, drank, cleaned with...

"five hundred brand-name household products -- cleaning agents and detergents, rug shampoos, cosmetics, nail-polish removers, insect repellents, paints, lawn fertilizers, cold remedies, cough syrups, herbal teas, coffee, even peanut butter."

The goal-oriented lawyers are relentless, and you can see the four-dog defense in play:

"Do you eat peanut butter?" one of Facher's young associates asked Anne Anderson.
"No," said Anne.
"Did you ever eat peanut butter?"
"I guess everybody living has probably tried it," replied Anne.
"Do your kids eat peanut butter?"
"Well, the same jar has been sitting there an awfully long time, so I guess we don't eat much"
"What kind is it, plain or chunky?"
"Plain, smooth," said Anne."
"You made your children peanut butter sandwiches?"
"They ate some, when they were small"
"When you say, 'some,' could you quantify that?" One or two sandwiches a week for the children?"

How does this apply to the chemical on trial and the deaths and illnesses that the communty was experiencing, you ask? Peanut butter can contain aflatoxin, a carcinogen. By cataloguing the everyday products that the plaintiffs used, then pointing to possible carcinogens that they contained, the lawyers could throw doubt of the cause of the TCE related illnesses. Clearly Anne hardly ever ate peanut butter. But here, the lawyer throws doubt on that. As Harr writes, Jan Schlichtmann, lawyer for the plaintiffs, knows that the defendant's lawyers are trying to dilute the evidence in order to develop uncertainty about the origin of the cancers. When at 5:00PM, he requests that the defense lawyers to end their deposition, they ignore him and continue their questioning.

"Do you eat bacon?...(Bacon contains dimethylnitrosamine, a carcinogen.) How often? How many slices? Do you fry it or bake it? Do you have Teflon pans (Teflon is made of a resin containing acrylonitrile, a carcinogen.) How often do you use them? Do you chew sugarless gum? (Saccharin, a carcinogen in mice.) How often? Do you pump your own gas?..."

It continues with each plaintiff, over the next three weeks -- do you bathe, shower, wear deodorant, own a cats, have plastic shower curtains, drink beer, smoke? Each activity or product contains certain carcinogens, and therefore passes on certain risks...

While the pre-trial "discovery" of "A Civil Action" drags on, people continue drinking TCE polluted water and breath TCE polluted air.

"Roland Gamache was dying of leukemia by the time his second deposition began. Neither he nor his wife could admit this to each other. But the lawyers all knew. In early October, Gamache did not have strength enough to get out of bed...."

And while these leukemia victims answer inquiries by lawyers working on behalf of TCE dumpers, somewhere else in the world, in another room, at another polished bird's eye maple conference table, lawyers for a different chemical or product question different plaintiffs about their possible exposure to solvents -- have you ever glued anything (glues contain can TCE)? Walked by the old Naval base in the next block?

In the end the Woburn case didn't repair the TCE victims, nor did it motivate universal action on TCE. But law schools use the book as a case study to instruct future lawyers prosecuting (as well as defending) the makers of toxic chemicals. As you can imagine then, with this sort of defense fully proven to work, people injured from environmental toxicants have a difficult time getting remedy from the courts.

The Doggy-Dog World of Politicians

Given the tenacity and success of the four dog defense, it was against great odds that after decades years of stalling, not only by industry and lawyers, but by politicians, White House administrations, and the Department of Defense and Department of Energy, the EPA released its final IRIS assessment of TCE last week.

The EPA's last assessment of TCE came in 1987, almost a quarter of a century ago. In 2001 the EPA calculated that based on research to that date, TCE was 5-65 times as toxic as previously thought, especially to children. It can be found in 761 Superfund sites. Since the Department of Defense and Department of Energy would be responsible for cleaning up many of the sites, the agencies fought vigorously to prevent EPA action. The Office of Management and Budget (OMB) reports that DOD action against the rule cost taxpayers a million dollars.

The EPA's path to updating the Toxic Substance Control Act (TSCA) is tortuous, likewise for the the EPA's completion of the IRIS assessments for the backlog of chemicals with suspected or proven health affects. The agency struggles to overcome a failed strategy of depending on industry to produce safety profiles of chemicals, a method of oversight that hasn't adequately safeguarded our health. (Acronym Required started reporting this here in 2005, decades into the battle ²). But progress gets perpetually hindered - as you can see, industry mounts gargantuan hurdles against the EPA.

Even once people are somewhat convinced that a chemical such as TCE is toxic, lobbyists for industry deploy the four dog defense. This is long after the media loses interest, long after the public tires of hearing about it, long after the environmental groups start in on their next action item, and long after most politicians drop the issue (now that they're not getting calls from their constituents).

As we speak, politicians that we (you) voted for, "working in our interest" actively fight against the EPA's IRIS assessments and against EPA moves to strengthen TSCA. Their most successful claim against regulating chemicals that cause the loss of life and impede people's ability to work? That the "stringent" rules will "cost jobs". Politicians are often lawyers first after all, so they know the four dog defense perhaps better than any of us.

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¹ "Can This Man Tame Tobacco?" David Barstow St. Petersburg Times April 7, 1997

² Acronym Required wrote about TSCA in of posts a couple of posts about Teflon in 2005; in a few posts on Europe's REACH, for instance The EU on Chemicals: More Strife Across the Pond?; a here and in many posts about bisphenol-A.

Mundane Data Breaches

Mistakes usually occur after a conflagration of seemingly small, quotidian errors. Often no one seems to own the problem, it's simply a "glitch". In our technological world, we're quite accustomed to glitches and large data integrity losses. We stick the newly issued credit card into our wallet before even knowing (or caring) about the details of why it was replaced.

Technology "glitches" are not to be trifled with though, they shut down metropolitan train systems, admit ~32,000 students instead of ~16,000, and compromise the most private data of 31,000 people, 100,000 people, 4 million people...They're just boring news.

In medicine, repercussions from computer glitches make train outages seem trivial. From August 2008 through February 2009, a computer glitch in the Veteran's Affairs record system tied patients to the wrong medical records, leading to incorrect dosing, delays in treatment, and other errors. A computer glitch in another case incorrectly cleared women of breast cancer after mammogram screens showed they actually had tumors.

Bodily Injury and Death

Imagine the most unimaginable "glitch" and it's probably already happened. In one, famous 1980's case (PDF), cancer patients undergoing radiation treatments from the Therac 25, manufactured by Atomic Energy of Canada (AECL), intermittently received radiation doses 100X the prescribed dose. The resulting radiation could burn through the torso and leaving a burn marks on the victim's back. The trauma from radiation trauma killed some patients within weeks.

An investigation of the Therac 25 history showed how multiple errors begot fatal injuries. The high doses occurred when a technician first entered an "X" to incorrectly select a certain dose of high beam photon mode; then "cursor up"; then "E" to correctly select a certain dose in the electron mode; then "Enter", all within 8 seconds. This accidental series of keystrokes activated the high beam instead of the low-beam, but the high beam diffuser wasn't in place, so intense radiation burned ears, breasts, groins, clavicles.

When it happened to one patient, the sound system between the treatment room and the operator wasn't functioning. He had been treated multiple times in the past, so knew something was wrong when as he lay on the table for treatment he suddenly heard unusually loud noises, saw a flash of light, and felt a searing burn. Pause. Then it happened again. The technician only learned something was wrong when the patient pulled himself off the treatment table and began banging on the locked door.

Because the burns happened infrequently, because the error messages were imprecise or oblique, and because technicians, engineers and managers couldn't believe the Therac 25 was malfunctioning, operators continued to injure patients until 1987. In a letter to one hospital physicist AECL explained that their machines couldn't be malfunctioning because of modifications that improved the "hazard rate" by "at least five orders of magnitude! With such an improvement in safety (10,000,000%) we did not believe there could have been any accelerator malfunction."

A glitch -- an "accelerator malfunction"? Or errors attributable to peoples' actions?

Errors Upon Errors

The persistence of medical physicists at several hospitals quickened Therac-25 problem solving, but clumsy safety processes, a reluctant manufacturer, and slow FDA action impeded resolution. In the final analysis, a long list hardware, software, quality assurance and process issues such as these, contributed to the injuries and fatalities:

• The hardware and software were built by two different companies and only tested when the system was installed in the hospital.
• Code wasn't independently reviewed.
• Some engineering errors permitted overrides after malfunctions, other errors allowed for safety check bypasses.
• The FDA hadn't thoroughly tested the Therac 25 (a medical device) because previous models had a reasonable safety record. But the Therac 25 had undergone numerous changes, for instance manual control systems transitioned to software controlled systems.
• The company recalled the machines at one point, but because the first patients didn't die, the FDA under-classified the severity of the problem. But an intense radiation beam to the head could result in a more lethal dose than another body part, so later incidents were fatal.
• The medical physicists and the FDA made recommendations to AECL. The company complied with some safety directives, but ignored others.
• Technicians incorrectly diagnosed issues, for instance in one case a problem was wrongly attributed to a switch. The company replaced the switches. The problem recurred.
• AECL wrongly told some institutions who reported incidents that theirs was the first report. So each hospital thought their case[s] unique.

Elusive Intangible Injury

In the Therac-25 case, each contributor -- a software programer, an engineer, a technician, someone in quality assurance, a safety officer, staff at the FDA, a company executive -- made a small mistake. Lawsuits, FDA investigations, out of court settlements, and eventually national media exposure brought the case attention. The entire compendium of errors in the Therac-25 case is so classic and dramatic that it's used as a case study. But what about computer glitches where less harm is done to fewer patients over a shorter period of time? Or what if so many are hurt - millions, say - that the plight of any one individual gets diffused? What if the evidence is unclear - there there are no burn marks on the front and back of the body?

Can injured patients be made whole? In Therac-25 cases, the lawyers of families of patients with terminal cancer argued that patients died sooner and suffered more because of their Therac-25 injuries.

What if doctors delay cancer treatment and the person dies an early death from breast cancer, as in the case we mentioned above? What can lawyers prove, how can victims be compensated? In the case where Veteran's Administration patients were matched with the wrong record, the VA denies that any negative outcomes. No harm reported, no harm done?

What about still "lesser" glitches, everyday database breaches?

Patients: Students of Misfortune?

The US HIPAA laws protect a person's medical data, file, or record from being accessed by an unauthorized person. Therefore someone couldn't enter your doctor's office, grab your paper record from the thousands stuffed floor to ceiling, and forward it on. Sometimes the law seemed overly strict. In the name of HIPAA, unmarried lifelong partners of hospitalized patients were forbidden from learning about their loved one's health.

Although HIPAA has provisions for electronic records, today's larger, more frequent mishaps leaves this regime seeming quaint. Consider the recent data breach at Stanford, where the emergency room records of 20,000 patients were posted on line. A New York Times article details how it happened. One billing contractor dealt with one marketing contractor, who interviewed one potential employee who leaked the data. The marketing contractor received got the data from Stanford Hospital, "converted it to a new spreadsheet and then forwarded it" to a job applicant, challenging them to

"convert the spreadsheet -- which included names, admission dates, diagnosis codes and billing charges -- into a bar graph and charts. Not knowing that she had been given real patient data, the applicant posted it as an attachment to a request for help on studentoffortune.com, which allows students to solicit paid assistance with their work. First posted on Sept. 9, 2010, the spreadsheet remained on the site until a patient discovered it on Aug. 22 and notified Stanford."

Would any of these patients know if they were harmed? What if they had some condition that an insurance company, employer, teacher or other would use to disqualify them as in this Stanford case? Will the class action lawsuit that's filed make them whole? What if someone recognized the value of such data and stole it, as in a recent Orlando, Florida case where hospital employees forwarded emergency room data for over 2,000 accident victims to lawyers? In the old days, hauling 20,000 patient files out of a doctor's office unobtrusively would be a challenge. Not so much with electronic data, all you need is a glitch.

HIPAA specifies that each responsible individual can be fined $250,000. Will the job applicant who outsourced her Excel Worksheet problem to StudentofFortune.com pay $250,000? The marketing contractor? The billing contractor? Stanford?

Often the public has no idea about medical injuries resulting from glitches, physical or otherwise, just as they didn't with the Therac-25. If someone dies, as in the Therac-25 case, perhaps the news will get out. But the more common the incidents, the more data is lost, the more are made to seem benign, the more harm is done, the less we learn about any particular incident.

You can read all this as a depressingly negative outlook on technology and health, but my view is different. Injuries and deaths due to vague "glitches" can be prevented by fixing small, but very tangible errors. The outsourcing of everything has increased the number of contractors, and with all these people, looser interpretations of rules and diffuse culpability. But it's not just contractors. Many employees are also very cavalier about data. Walk-in or call any major medical center and you will see glaring errors. Fixing such errors, attention to detail, and yes - support for regulatory oversight, can reduce harm.