When worlds collide: Wakefield, ethics, & where I live

The News of the Day is that the British Medical Journal has called Andrew Wakefield’s notorious and notoriously retracted vaccine-MMR study “fraud.” That’s something a lot of people had already figured out, but with the imprimatur of BMJ, I guess this makes it official.

Ah, it takes me back, though. To the time I dined with Andrew Wakefield. To that day that the Lancet issued its full retraction of that horrific, fraudulent trash heap of a paper.  To that satisfying few hours of schadenfreude when the GMC handed down its decision to strip him of his license. To my various other Andy sightings about town. To the real horrors of what he wrought when he did what he did to those children in that study.

I’ve posted a lot about Wakefield on my personal blog, and some of the posts have focused on my anger at his bastardization of science and my musings on how people might feel when they falsify data. They’ve included mapping what the enormity of the alleged conspiracy against him would have to be and breaking down with tongue firmly in cheek his plea to make his book of apologia a bestseller. There was the post that I swore would be My Last Word on Wakefield (it wasn’t).

Finally, there is what I taught my son today. We’re studying science–Science–and we were discussing the qualities that make one a good scientist. Sure, there’s curiosity. Creativity. And…there’s honesty. For that and that alone, I close with my defense of ethics in science, why ethics matter, and why I think someone who perpetrates this level of harm to public health ought to be somewhere away from his comfortable, ultra-expensive home just a stone’s throw from where I live. Preferably a quiet place, perhaps with four bare walls, a place where he can ponder the damages he’s wrought.

NPR’s Asperger’s FAIL

NPR’s “All Things Considered” ran a piece today on the difficulties in defining “mental disorders.” Based on what is posted on their site regarding the piece, they essentially report the opinion of one man, Allen Frances, who has taken it upon himself to do two selfish things. The first is that he blames himself for what he calls the “Asperger’s epidemic.” The second is that he felt compelled to discuss some unfounded–or at least, unsupported–assumptions about Asperger’s diagnoses on NPR.

Frances, former chief of psychiatry at Duke University Medical Center, was the editor of the previous edition of the “mental disorders” bible, the Diagnostic and Statistical Manual of Mental Disorders. We’re coming up on the fifth version of this hefty tome. From my personal experience, by the time it comes out, research will be about five years ahead of much of what it contains. But never mind that. Frances’ issue with IV was that it contained Asperger’s as a diagnostic category (he has other issues not addressed in the NPR piece). He describes having acquiesced in its inclusion based on needs expressed by professionals who were seeing children with autism-like behaviors that weren’t as severe as the disorder known as autism.

Now he regrets that. Why? Because so many children are now being diagnosed with Asperger’s. As the parent of a child with autism, as the friend of many families with parents or children with autism, as the acquaintance of many grown people with autism–including Asperger’s–I can say that many of us would perceive that increase as a good thing. Why? Because that means more people with autism are able to recognize what makes them tick, and it helps them to know that yes, in a world where many of us feel like Temple Grandin’s aptly described “anthropologist on Mars,” there are a lot of other like-minded anthropologists out there.

That’s not Frances’ take. Based on a study done at the time IV was formulated, Asperger’s was “vanishingly rare.” That’s not too shocking given that for most professionals, it didn’t exist yet. The explanation that he offers for the increase in Asperger’s cases isn’t that there is now a diagnostic category for it, but that people–parents, presumably–seek the diagnosis so that their children can get services at school. This part is worth quoting from the piece:

“And so kids who previously might have been considered on the boundary, eccentric, socially shy, but bright and doing well in school would mainstream [into] regular classes,” Frances says. “Now if they get the diagnosis of Asperger’s disorder, [they] get into a special program where they may get $50,000 a year worth of educational services.”

The clear inference to draw from this is that there are hundreds of medical professionals out there deliberately stretching the diagnostic checklist for Asperger’s to cover children who are “doing well in school” and who are “socially shy” (what other kind of shy is there?). I have a few problems with this scenario.

First, if your child is doing well in school, you don’t get services. Services are for academic support. Period. There aren’t “special programs.” A child may have academic supports from almost nothing to a full-time aide in an integrated classroom to exclusion in a resource classroom. There is no one “special program.” That’s one reason they call those things INDIVIDUAL education plans. Regardless, if you’re doing well academically, you don’t get these supports. If you have speech or motor deficits, you receive appropriate therapies. But the deficits have to be there–they’re not something you just make up.

Second, if your child is doing well in school, parents and schools and medical professionals don’t generally go looking for a label to slap on the child. Parents seek help because their child has a problem or problems. The gold standard for calling something a disorder is if it interferes regularly with the general processes of daily life. Doing well in school but being “shy” doesn’t meet that standard. With autism, with Asperger’s, we’re talking about debilitating, meltdown-inducing, terror-filling anxiety. There is a difference.

Third, I don’t have a clue where he got the monetary value from, and NPR provides no balance for that statement. It’s just sitting there, making any family with a child receiving any services look like a faking money suck. Nice.

The piece as presented on the NPR Website provides nothing in the way of confirmation from objective sources. No studies indicating overdiagnosis. No input from experts in autism confirming what Frances says. His off-the-cuff commentary, his self blame, his stirring the pot all just sit there, unchallenged. Even the apparent effort at “balance” at the end of the story is almost a non-sequitur, part of a story with no real core. It’s as though they can’t make up their minds about whether the piece is about difficulties of diagnosis in general, the blurred lines between disorder and merely discombobulated, or that Asperger’s in particular is an overdiagnosed condition.

They don’t even provide Frances’ qualifications to speak to autism in particular. Not all doctors are oncologists, and not all psychiatrists have a deep understanding of developmental disorders.

All in all, a shoddy presentation that is already making its way around the Twitterverse, with parents once again feeling as though they have to defend their child’s diagnosis of a developmental difference that often goes unseen. Here’s the deal: The diagnostic criteria are clear, and a child who’s merely eccentric and doing well in school does not fit those criteria. If there is some modicum of overdiagnosis, it’s certainly not because of parents overseeking a label so they can have their child be stigmatized at school by receiving services. Look to the diagnosticians to blame. Or, in the complete absence of any evidence from Frances himself or NPR, do what Frances asks and blame him. Given his focus on his regrets over IV, he clearly seems to have something to expiate. And so does NPR. I’ll turn to D.H. Lawrence and say that thing is…a pettiness.

Autism, SHANK, and busy highways

Two autism studies in the news. I’ve summarized them at the Thinking Person’s Guide to Autism here. Let’s just say that the headlines, stories, and news releases have hyped yet again. Indeed, the title of this post should’ve been: “Headlines hype, news releases overpromise again in autism research.”

The worst offender is easily, “Proximity to freeways increases autism risk, study finds.” Um, no. The study found that autism rates are higher among people living within 309 meters of freeways. That in no way means that living close to a freeway increases autism risk. It’s a common, basic overinterpretation of correlation and epidemiological conclusions, but it’s really starting to get old. You can read more about the fuzzy definition of “freeway” and “major road” here.

Microbes redirect our best-laid plans

Greeks at War (pottery from the British Museum; photo courtesy of Wikimedia Commons)

The madness of King George

Timeline, 2006: It’s not that unusual for disease to alter the course of history–or, history as humans intended it to be. Some scholars believe, for example, that the intransigence of King George III of England arose from his affliction with porphyria, a heritable metabolic disorder that can manifest as a mental problem, with symptoms that include irrational intractability. But it’s rarer for a disease to shift the balance of power so entirely that one nation gains the upper hand over another. Yet that appears to be what happened to the city-state of Athens just before the Peloponnesian Wars of around 430 B.C. The upshot of the wave of disease and the wars was that Sparta conquered Athens in 404 B.C.

Spartans had a little microbial assistance

Sparta may have owed its big win to a small bacterium, Salmonella enterica enterica serovar Typhi, the microbe responsible for typhoid fever. A plague swept across Athens from 430 to 426 B.C., having traveled from Ethiopia to Egypt and Libya before alighting in the Greek city and destroying up to a third of its population. In addition, it brought to a close what became known as the Golden Age of Pericles, a time when Athens produced some of its most amazing and widely recognized art, artists, and philosophers, including Aeschylus, Socrates, the Parthenon, and Sophocles. Pericles was a statesman who oversaw the rebuilding of Athens following the Greek win in the Persian Wars, and he guided the city-state to a more democratic form of rule and away from the dictatorships of the previous regimes. In the process, the city flourished in art and architecture.

And then along came the plague. The Greek historian Thucydides, who chronicled the Peloponnesian Wars, left behind such a detailed account of the plague, its symptoms, and what happened to its victims, that intrigued medical detectives have ever since debated about what might have caused it. Thucydides, himself a plague survivor, vividly described the sudden fever, redness of the eyes, hemorrhaging, painful chest and cough, stomach distress, and diarrhea that ultimately led to death in so many cases. He also mentioned pustules and ulcers of the skin and the loss of toes and fingers in survivors. This litany of symptoms produced many candidate causes, including bubonic plague, anthrax, smallpox, measles, and typhoid fever.

Construction crews yet again uncover something interesting

In the mid-1980s, a construction crew was busy digging a hole for a subway station in the city of Kerameikos when they uncovered a mass burial site. Unlike other Greek burial sites, this one bore marks of hasty and haphazard burials, and the few artefacts that accompanied the bones dated it to the time of the plague that destroyed Athens. Researchers were able to harvest some teeth from the site and analyze the tooth pulp, which retains a history of the infections a person has suffered. They examined DNA sequences from the pulp for matches with suggested microbial agents of the plague, and finally found a match with the typhoid bacterium.

Typhoid Mary: Intent on cooking, ended up killing

One discrepancy between the disease pattern of typhoid fever and that described by Thucydides is the rapidity of onset the Greek historian detailed. Today, typhoid fever, which still infects millions of people worldwide, takes longer to develop in an infected individual, and sometimes never develops at all. People who bear the virus but don’t become ill themselves are “carriers.”

Perhaps the most famous carrier was Typhoid Mary, Mary Mallon, a cook in New York City at the beginning of the 20th century. It is believed that she infected hundreds of people, with about 50 known cases and a handful of deaths being directly associated with her. Typhoid Mary was told not to work as a cook any longer or she would be quarantined, but she simply disappeared for awhile and then turned up under a different name, still working as a cook. After another outbreak was traced to her, she was kept in quarantine for 23 years until she died.

Bisphenol A: multisystem effects

These bottles were produced without BPA in response to concerns about the chemical. Photo via Creative Commons, attributed to Alicia Vorhees, thesoftlanding

Are endocrine disruptors stealing our future?

Endocrine-disrupting compounds are chemicals in the environment—usually compounds that we have introduced—that can alter normal hormone signaling processes. Often, exposure to these compounds has little immediate effect in adult animals, but it can have big effects on organisms during sensitive developmental periods, like embryogenesis. During embryonic development in vertebrates, steroid hormones govern many processes, and the fetal hormone environment is usually carefully calibrated to ensure that these processes go forward normally.

Tiny amounts, big changes

But many compounds disrupt these processes, knocking them off track and resulting in development that is unusual or abnormal. For example, male alligators exposed in the egg to these compounds—which often persist in fatty tissues or yolk—emerge with serious penile abnormalities that can affect their ability to reproduce. The banned pesticide DDT is probably one of the best-known of these compounds, and exposure to it or its metabolites has been shown to disrupt hormone signaling to the point of altering sex development completely.

When we think of hormones, we often think of puberty, the time when hormones seem to govern our every move. When we think of estrogen, we probably think “female” because estrogen has historically been considered the “female” hormone. What you might not know is that estrogen, which is made in the ovaries, is also made in our brains during embryonic development. In mammals, appropriate male development appears to require neural estrogen synthesis. When estrogen synthesis in embryonic mammals is blocked, the males that develop do not exhibit typical male behaviors when they reach reproductive maturity.

Bisphenol A: ubiquitous chemical

Among the compounds that have been identified as endocrine disruptors is bisphenol A (BPA). In the United States, we produce about 2 billion pounds of BPA a year. Previous studies have demonstrated that BPA can disrupt thyroid signaling to the point of affecting the thyroid’s role in appropriate brain development. In addition, BPA has been linked to feminization of reptiles. Some scientists were aware of BPA’s hormone-activity potential as far back as the early twentieth century.

But because no one took that knowledge or its potential seriously—the field of endocrine disruptors is relatively young—BPA has found its way into almost every aspect of our lives. It is in the dental sealants we put on our teeth to keep the cavities at bay. It is in the lining that coats the insides of food cans to keep the metal from rusting. It is in the hard plastic that we use for baby bottles and teething rings. And it can leach from these products into the food that we eat. BPA is found at high levels in some pregnant women, and it appears to accumulate in higher concentrations around the umbilical cord and in the fetal amniotic fluid.

BPA and effects on the developing brain

Work from Yale and from researchers in Japan also points to some potentially serious effects on the brain. Part of the role of estrogen in brain development is facilitating synaptic connections in a crucial brain area called the hippocampus. The hippocampus is the center where neurons organize that will later be activated to produce sex-appropriate activity in vertebrates. It is also the area of the brain involved in the formation and retention of memory.

The researchers found that small doses of BPA—doses that fall within EPA-approved levels for exposure—can inhibit hippocampal synaptic formation in rats, counteracting the effect of estrogen. That BPA is an estrogen inhibitor could be serious for our brains if the results translate into human effects. As we age and our endogenous estrogen levels decrease, for example, the hippocampus suffers and our memory does, too. If BPA sets this process in motion even earlier, hippocampal—and thus, memory—decline may occur even earlier.

Rodents, monkeys, and people–oh, my

A recent report in Environmental Health Perspectives concludes that rodents, rhesus monkeys, and people all exhibit similar pharmacokinetics with BPA and that exposures may be far greater than previously calculated. Other recent studies suggest effects on sugar metabolism related to diabetes, an association with polycystic ovarian syndrome in rats, and a relationship to the development of asthma in a mouse model.

Just eat the broccoli, preferably steamed

A presidential/vegetable debacle

When the first President Bush indicated a distaste for broccoli during his presidency, he set off a firestorm of vegetable-based controversy. Broccoli haters sympathized, but nutritionists were horrified. Turns out, the data are all on the side of the nutritionists.

Research has shown that people who eat cruciferous vegetables—for example, broccoli, cabbage, or cauliflower—have lower rates of cancer. Armed with this information, researchers around the country have sought the cancer-fighting ingredient in broccoli and tried different ways to maximize the benefits we can get from it.

Yes, it’s got healthy stuff in it

They pinpointed the compound of interest in 1992. It is sulforaphane, a phytochemical in a group called the isothiocyanates. These compounds are known to induce apoptosis, or programmed cell death, of cancer cells. Epidemiologists—people who trace and track diseases and their causes—have found lower rates of prostate cancer in men who eat diets high in isothiocyanates. Scientists found that the way we release these cancer-fighting compounds from our veggies is to cut or chew them.

Sulforaphane, one of the most powerful anticarcinogens—anti-cancer compounds—in our food, works through the liver. Our livers are responsible for detoxifying our bodies, which happens in phases. In some cases, liver enzymes can actually turn compounds into carcinogens. But our phase II liver enzymes break down toxins before they can damage our DNA, the molecule that houses our genetic code. Sulforaphane boosts these phase II enzymes, thus wielding its anti-cancer power.

Broccoli pill–or just broccoli?

When the world found out broccoli’s secrets, there was a craze for broccoli-derived supplements that contained sulforaphane. Broccoli-based pills, powders, and teas hit the shelves, and people everywhere crunched into broccoli, possibly wincing like our former president might have as they chewed it up and forced it down. But what they may not have realized is that mature broccoli also has some compounds help liver enzymes that turn compounds into carcinogens. The goal was to find a way to deliver sulforaphane without delivering too much of these less-benign accompaniments, or too much sulforaphane, which can be toxic in large amounts.

One approach was to synthesize a sulforaphane that retained its anti-cancer powers, but was not as toxic in high doses. This compound is called oxomate, and it has been successful in the lab in reducing breast tumors in rats. Another approach was to try to find a broccoli growth stage that made sulforaphane in reasonable amounts, but that did not produce the compounds that elicited the liver’s carcinogen-producing enzymes. Scientists following that line of research discovered that broccoli sprouts, tiny alfalfa-like sprouts grown from broccoli seeds, contain abundant and safe levels of sulforaphane, but do not synthesize the unwelcome compounds that boost carcinogenesis.

When proteins attack

But one thing that food scientists had found was that even when broccoli was consumed, its sulforaphane could be immediately disabled by broccoli protein called the epithiospecifier protein. Sulforaphane in the plant is attached to a sugar via a sulfur bond. When we cut or chew the broccoli, we can activate the enzyme that breaks the sulforaphane off of the sugar. But then there’s that sulfur flapping in the breeze, and the epithiospecifier comes along, yanks off the sulfur, and inactivates the sulforphane. Food researchers have found that cooking broccoli for 10 minutes at 140 degrees Fahrenheit kills off the epithiospecifier protein, leaving behind intact sulforaphane and the enzyme that releases it from the sugar to do its good work in our bodies.

So if you’ve been choking down overcooked broccoli all in the name of health, you may have been reaping the benefits of fiber or other broccoli-derived nutrients, but you weren’t getting much sulforaphane out of it. Your best bet, according to researchers, is to steam fresh broccoli for about three or four minutes and eat it, cheese sauce optional.

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