Last year, a Congressional panel met to discuss consumer genetic testing. Some of the speakers issued statements that were so factually inaccurate as to be offensive; then, they largely concluded that people should be protected from their own curiosity. This week, an FDA panel met to discuss consumer genetic testing. Some of the speakers issued statements that were factually inaccurate and in one case plain offensive; then, they largely concluded that people should be protected from their own curiosity.

When I wrote a six-part series about consumer genetic testing last year for Newsweek, I was not an advocate on either side. (At least I didn’t start out that way.) Now I find myself squarely in one camp and sorely disappointed in the way the dialogue on the issue has played out over the last few months. What motivated me to write about the issue in the first place was a feeling that consumers were being left out of a debate that was supposed to be about them. Critics in Congress and the GAO were concerned that people would mistakenly treat their necessarily incomplete genetic data sets as crystal balls, but how many customers were actually invited to the Congressional hearing to share how they might think about their results? None. This time around, at the public meeting, how many consumers were expressly invited to speak? None. It’s hard to see how people in power could ever look fairly at consumer genetic testing, given that every time they tackle the issue they end up having the same conversation without bothering to get direct input from the people whose welfare they’re purporting to protect. UPDATE: After the meeting, the FDA held an official public comment period. This was a great way to to get consumer input, and the agency should be commended for it. 

So here I am again, waving my hands and jumping up and down, trying to provide some of that input.

Last year, I was a potential consumer of genetic scans. Now I’m a current consumer. I bought a kit from 23andMe in August; when I got my SNP list back, I sent it off to deCODEme for a generously donated second opinion. And — attention, FDA! over here! — I found out something earth-shaking.

It wasn’t that I’m at dramatic risk of Alzheimer’s, which was the only bad news I thought I might get. Turns out that 23andMe doesn’t test for variants, or SNPs, in APOE4, which is the gene that could have told me such a thing. Scientists can often figure out what a genetic variant is without directly testing it, by examining other nearby variants — this is called imputation — but for technical reasons, APOE4 data apparently can’t be imputed from the information I have. The upshot is that if I’m carrying a variant that might dramatically increase my risk of Alzheimer’s Disease — an illness to which several of my relatives have succumbed — I have no way of knowing, at least not from these results.

It wasn’t that I have a very high or low genetic risk for any other common disease. Best I can tell from these results, I don’t. I suspected that already based on family history. My SNPs are just as “delightfully uninteresting” from a medical perspective as I expected them to be.

I did have two health risks that appeared in bold red text at the top of my 23andMe results list. I suppose that bold red text might have scared me if I hadn’t read the thin black text that was intended to explain it. But I had paid $500 for the thin black text. So I read it, and I reread it, and I cross-referenced it with my deCODEme report, and I clicked on the links to studies, and I did some literature searches of my own. Here is what I concluded:

(1)    For the first bold red risk — atrial fibrillation — the results were based on two SNPs. Neither by itself correlates with a dramatic rise in susceptibility. (Also, I have only one of the high-risk SNPs; my other associated SNP is actually linked to a slightly lower risk than average.) Both SNPs are in the same gene-poor region of chromosome four. Nobody knows what they do, biologically. One thing scientists do know is that other genes have been and will be linked to atrial fibrillation. None of these other genes were tested in my results. If they had been, who knows what would have shown up? It’s possible I’m not at high risk for this disease at all, especially since I have none of the known environmental risk factors. In short: I’m not terribly worried.

(2)    The second bold red risk was for Restless Legs Syndrome. According to 23andMe, 4.2 out of every 100 European women develop RLS; among those with a particular variant on chromosome six, which I have, 5.2 out of 100 will. (This in and of itself made me skeptical. More than four percent of European women have this disease? I’m willing to believe the illness is real, but might it be overdiagnosed? Why, yes, it might be.) Unlike my atrial fibrilliation SNPs, this variant is in a gene, albeit in a non-coding portion. 23andMe does an excellent job of explaining what that may mean: “The function of this gene is not yet known. Scientists do know that it belongs to a large family of genes that encode proteins that can influence activity levels of other genes. The SNP in this gene doesn’t actually cause a change in the protein sequence of BTBD9. Instead, it lies in a non-coding part of the gene where it may affect how BTBD9 is turned on or off.” In other words, I have one variant that may help regulate one gene that regulates other genes; this variant is linked to a polygenic disease for which the background rate is in dispute. Gosh! Forget Restless Legs Syndrome; isn’t this knowledge going to keep me up at night? No. No, it’s not.

These were the only two higher-than-average risks in my report. My analysis of the rest of my risks proceeded along the same lines — which were lines that anyone with an ounce of sense would follow. To wit:

Hey, I have a lower-than-average genetic risk of melanoma! Except I might not, seeing as how my 23andMe results are based on just two SNPs (does anyone think cancer is caused by two genes alone?). Given that there is melanoma in my family, and given that I’m a white girl who regrettably got burned to a crisp on a regular basis in childhood, I’ll keep wearing sunscreen.

This just in: my AA status at the SNP rs7590720 suggests I’m at “typical odds of alcohol dependence in men!” Except I might not be in real life, because alcohol dependence is not a Mendelian trait and I’m not a man.

Cool, I’m AA at rs363050! According to 23andMe, a 2006 candidate-gene study of 667 Dutch subjects showed that for each A at this site, non-verbal IQ goes up three points. But candidate-gene studies often fail to replicate. (Small quibble with 23andMe: Why cite candidate-gene studies on such a complex trait, especially in the era of GWAS? Maybe an appropriate role for regulation would be quality control, assuring that the literature cited is sound.) Besides, IQ is presumably affected by all kinds of things. This result is useful only for making jokes about one’s prowess at Sudoku, and one doesn’t need to be AA at rs363050 to see why.

What else? I’m slightly more sensitive to Coumadin than average and slightly less sensitive to Plavix. I’ll bear that in mind if I ever need an anti-coagulant — but for now, I’ll content myself with learning more about how anti-coagulants work. There’s some fascinating stuff there, starting with the fact that Coumadin was invented as a rat poison.

I carry none of the rare recessive variants that I got tested for, except for one linked to hemochromatosis. Were this a disease-causing variant, I might ask my husband to get tested, too, but my variant is mild. The only consequence of my carrying it, and finding out that I do, is that now I’m interested in hemochromatosis.

I had a blast figuring all this out. And I didn’t need a doctor to help me do it. Actually, sitting in a doctor’s office trying to sift through the data would have been less fun and almost certainly impossible, as I’m sure my primary care provider has much better things to do than babysit me while I look at PubMed.

Now that I have my results, I can’t help but laugh at myself a little, or at least at the version of myself I used to be. Listen to me back in August, agonizing over whether I really wanted to check out my own DNA: “When I finally pulled my testing kit out of its box, [I] found to my complete surprise that I was — there’s just no other word — scared of it. … Whether or not the test qualifies as a medical device under FDA rules, it looks like one. It has a biohazard sticker on it!”

Why on earth was I so scared? What was it that caused me to see my own spit as a biohazard? If you had asked me back then, I might have said something like “emotion” or “irrationality.” Now, I know that this particular type of irrationality has a name: “genetic exceptionalism.” It’s defined as “the idea that genetics must be treated as special under the law,” and it’s largely based on the unfounded belief that DNA is more powerful than it actually is, to the point of being magical.

I don’t know why genetic exceptionalism is so common and reflexive. I don’t know why so many people seem to naturally approach DNA with fear and awe. Maybe it’s because almost everyone is introduced to genetics through Mendel’s pea genes, which really were individually powerful in their effects on phenotype; maybe the lesson people subconsciously absorb is “all genes work like that.” Or maybe it’s just because of GATTACA.

Maybe it’s because DNA really is special in a number of ways. It is a biochemical form of literature, a Great Natural Novel that tells a story of life. (Not the whole story, by any means. But a good story.) It is elegant and beautiful.

But it is not magical or all-powerful, and if we are ever going to make responsible policies around it, we have to stop thinking of it as such.

Here is the earth-shaking thing I found out: It is possible to stop thinking that way. Reason can overcome emotion. People can approach information about DNA, even their own DNA — information that they might naturally find scary — and come to realize that there is nothing to fear because they see it in cold clear light for nothing more than what it is. I know people can do this, because it’s what I did.

Genetic exceptionalism is the default, the state of ignorance. How do you combat ignorance? By enabling knowledge. By giving people information and showing them what it may mean for their lives. By, say, appealing to people’s inherent curiosity about themselves, and then handing them a document that shows — that cannot help but show — that genes aren’t destiny.

This is precisely the information that bad regulation would keep out of the hands of consumers.

What will happen if we, as a society, confirm people’s misconception that genes are all-powerful, and if we tell them they are too stupid to understand their own data? They will come to believe that genes are all-powerful and that they are stupid. It’s a self-fulfilling prophecy. Whatever you think of consumer genetic testing, there is nothing that can turn up in a scan of a few hundred thousand SNPs that is anywhere near so frightening.

Michael Pollan, the well-known writer on food and agriculture, is a smart guy. His arguments tend to be nuanced and grounded in common sense. I like his basic maxim on nutrition – “Eat food. Not too much. Mostly plants” – so much that I recently promoted it in a Newsweek cover story. He’s the last person I’d suspect of reactionary thinking, which is why I wish I didn’t have to say this: Michael Pollan has made a deeply unfortunate mistake.

A few days ago, speaking to his 43,000 followers on Twitter, Pollan linked to an essay written by an environmental advocacy group that spends much of its time fighting the depradations of Big Agriculture. Curiously, the essay wasn’t about ecological destruction or even about agriculture. It was about human genetics. It argued that since genetics currently can’t explain everything about inheritance, genes must not influence the development of disease, and thus the causes of illness must be overwhelmingly environmental (meaning “uninherited” as opposed to “caused by pollution,” though the latter category of factors is part of the former one). This was a little like arguing that your engine doesn’t power your car because sometimes it breaks down in a way that confuses your mechanic — and concluding that gasoline alone is sufficient to make a car with no engine run. But Pollan took the argument at face value. He said it showed “how the gene-disease paradigm appears to be collapsing.” He was troubled that its contentions apparently had gone unnoticed: “Why aren’t we hearing about this?!”

Perhaps unknown to Pollan, the human genetics community – or at least the small, vocal part of it that is on Twitter – had in fact heard about this. It set about dismantling and dismissing the essay’s chief conclusions, which were at best overstated and at worst flatly wrong. A number of people outside the genetics community also must have seen the essay. Maybe some of them read it and thought, “huh. My kid looks just like me, but these people are saying genotype has little to no effect on phenotype. Do they really think my kid has my distinctive Roman nose because he grew up in my house?” Maybe some of them wisely thought, “hmm, I was taught that nature and nurture both mattered, this can’t be right” — i.e., don’t you need the engine and the gasoline? — and moved on.

But Pollan’s tweet lent the essay prominence and credibility. Since then, the Huffington Post has jumped on the meme, declaring with typical flair that genomics may just be “one part boondoggle, one part conspiracy by the military-industrial establishment.” The very respectable Marion Nestle has also joined in, tweeting enthusiastically about the “study,” which is no such thing. (It’s an opinion piece on a website, just like this blog post.) Who knows how many people have now seen the essay and been misled into thinking that science has shown the “environment must be the entire cause of ill health?” Who knows how many people far too savvy to subscribe to genetic determinism are now espousing “environmental determinism?”

It’s been more than a week since Pollan’s tweet – which, in Internet time, is an epoch – and he’s said nothing else about the topic. The essay is probably fading away. But I fear the thinking behind it isn’t going anywhere. This looks to me like the first (or maybe the second) flare-up in what may be a new iteration of the nature-nurture debate, which scientists abandoned decades ago as a false dichotomy but which apparently has never disappeared from popular imagination. It’s an iteration in which both sides will speak the language of science but only one will hew to its principles – a debate that could quickly come to resemble the “controversies” over autism/MMR and intelligent design. It will probably center on the issue of missing heritability, which is complicated and messy and lends itself to abuse. And if it does come to pass – if this essay is not an anomaly but a harbinger – it’s going to involve a whole lot of woo.

Well-crafted woo, at that. The argument in the essay – which boils down to “genetics is a work in progress, therefore genes don’t matter” – appeals to many people’s desire to focus on what can be changed (environmental factors) as opposed to what can’t (one’s genetic sequence). It slyly paints geneticists — and indeed, “medical researchers” in toto — as determinists, despite the fact that it’s practically impossible to be a determinist if you work on complex-trait inheritance, as Dan MacArthur has observed. It’s aimed at well-educated people who are naturally suspicious of the “military-industrial complex,” and people who have never had any particular reason to learn how heritability is calculated because they’re busy doing other important things. And it’s counterintuitive and anti-authoritarian in an extremist but oddly appealing way, one that sounds so populist as to resemble the rhetoric of both the Huffington Post and the Tea Party (“all those big-deal geneticists are WRONG!”).

This type of argument could present an enormous challenge for human geneticists, putting them on the defensive for research that should not need defending — and doing so in a way that’s very hard to counter without coming across badly. Sneering at denialists doesn’t work. It only feeds their momentum (“all those big-deal geneticists are SNOBS!”). Calmly explaining the facts doesn’t always work, either, as vaccination advocates and evolutionary biologists have learned over the years.

Last Thursday, I tried to put together a rebuttal of the essay as part of a 15-minute crash course in the basics of human genetics and genomics. After I gave the talk, I put it on the web. (I’m not sure it worked and would appreciate feedback. Also, it cuts off abruptly at the end because I forgot to ask people if it was OK to include the Q&A period and because YouTube doesn’t like videos longer than 15 minutes.) The presentation discusses GWAS design and heritability, present and missing. It touches very briefly on some directions for future genetic research: rare/less-common variants, copy number variants, gene-gene interaction, gene-environment interaction, etc. It considers how much the “missing heritability” debate will matter in the long run. And it does a wee bit of fact-checking the essay, albeit mostly by citing other people’s arguments.

But I don’t expect all that many laypeople, save my captive audience from last Thursday, to pay attention to the point-by-point part of the rebuttal. Who outside the field has the time or will to burrow so deeply into statistical genetics methodology when there are jobs to be done, kids to be raised, lives to be lived?

What I do want people to see is the 10:55 mark, where I try to engage with the essay on a level that doesn’t require any understanding of genomics — because I think this may be a way of explaining what’s wrong with it that speaks to a wider readership. Aside from its factual misinterpretations, the essay makes two logical errors that anyone can see if he looks hard enough:

1. It assumes that absence of evidence is evidence of absence, concluding that because common diseases aren’t caused by a handful of genes with strong effects, they aren’t influenced by genes at all. This is clearly a silly position, but it’s a handy one if you are, say, a group that wants to raise the profile of biomedical research into non-genetic factors such as pollution, and if you’re concerned about money being poured into genetic research at your expense. (For the record, I agree that research into environmental factors is important. Maybe the essay’s authors and geneticists should be lobbying together against pending cuts to the NIH? To borrow a malapropism from someone with whom I disagree on almost every other point: shouldn’t we make the pie higher?)

2. It mistakenly portrays science as a monologue, and a dull one at that. First, it lists some of the potential hiding places for heritability that remain in the genome. Then it notes that a few scientists think some of them are less likely candidates than others and that there’s no consensus that one of them will explain everything. This is presented as evidence that almost all of human genetics is in crisis. But the data has just begun to be generated, and of course it’s unlikely that one type of factor will explain everything. Life, in biology as elsewhere, is complicated. (As geneticists freely point out: take it from David Altshuler, Leonid Kruglyak, and a bunch of other people who would know.) We’ve seen this line of “minor disagreement = major crisis” argument before, from creationists who conscripted Stephen Jay Gould and punctuated equilibrium as “evidence” that natural selection wasn’t a widely accepted principle. It was just as absurd — and effective — a rhetorical tactic then as it is now.

Why do I think these parts of the rebuttal are the most important ones? Because if this essay is indeed the first volley from a new, “environmental determinist” movement, the technical flaws it contains are not going to matter in terms of public opinion. Laypeople aren’t going to have the time to learn the nitty-gritty details of how genomic research is done, and they will react poorly to anything they perceive as condescension from geneticists. As they should: Condescension is bad.

But ultimately, the essay itself — really, the entire “genes don’t matter” argument — is what’s condescending. It starts from a couple of philosophically flawed premises, papers over the holes with something that looks and sounds like science, and assumes that its readers, lacking technical expertise, are unable to see that the conclusions are not reality-based.

Call me an optimist, but I think many readers are smarter than that. And if I were a typical reader — if I weren’t closely acquainted with the scientific literature — I’d be angry to find that people purporting to enlighten me were in fact trying to snow me. (“Hey, this environmental-determinist advocacy group is WRONG!”) Or at least I’d want someone I respected — someone with, say, 43,000 followers on Twitter — to set things right.

Here’s a suggestion for how to do that in fewer than 140 characters: “Genes matter. Not too much. So does the environment.” Over to you, Mr. Pollan.

Max Blake was 7 the first time he tried to kill himself. He wrote a four-page will bequeathing his toys to his friends and jumped out his ground-floor bedroom window, falling six feet into his backyard, bruised but in one piece. Children don’t really know what death is, as the last page of Max’s will made clear: “If I’m still alive when I have grandchildren,” it began. But they know what unhappiness is and what it means to suffer. On a recent Monday afternoon, Max, now 10, was supposed to come home on the schoolbus, but a counselor summoned his mother at 2:15. When Amy Blake arrived at school, her son gave her the note that had prompted the call. “Dear Mommy & Daddy,” it read, “I am really feeling sad and depressed and lousy about myself. I love you but I still feel like I want to kill myself. I am really sad but I just want help to feel happy again. The reason I feel so bad is because I can’t sleep at night. And dad yells at me to just sleep at night. But, I can’t control it. It is not me that does control it. I don’t know what controls it, but it is not me. I really really need some help, love Max!!!!! I Love you Mommy I Love you Daddy.”

This is the story of a family: a mother, a father and a son. It is, in many ways, a horror story. Terrible things happen. People scream and cry and hurt each other; they say and do things that they later wish they hadn’t. The source of their pain is bipolar disorder, a mental illness that results in recurring bouts of mania and depression. It is an elusive disease that no parent fully understands, that some doctors do not believe exists in children, that almost everyone stigmatizes. But this is also a love story. Good things happen. A couple sticks together, a child tries to do better, teachers and doctors and friends help out. Max Blake and his parents may not have much in common with other families. They are a family nonetheless. That is what has mattered most to Amy and Richie Blake since Oct. 31, 1997, the day their son took his first ragged breath.

Max came into the world with a hole in his heart. Struggling to be born, he lost oxygen, and doctors performed an emergency C-section. Recovering from the operation, Amy feared her infant son would need surgery, too, but the doctors said the hole would close with time. Four days later the Blakes wrapped their baby in a blanket and brought him home to their little house in Peabody, Mass. Richie, a former Marine, was working as a county corrections officer. Amy was a promising divorce lawyer at a firm in nearby Boston. As children, both Richie and Amy had watched their parents split up, but they had found a comfortable routine in each other: he played straight man to her comic. Marriage suited them. Amy hung a large, sunny wedding portrait in the living room. Starting a family would not be easy: there were no grandparents living nearby, and Amy could take only three months of maternity leave. Still, she thought, this was a stable home, one where Max would be safe and happy.

The mothers of bipolar kids often say their babies are born screaming. These are children who live at the extremes: so giddy they can’t speak in sentences, so low they refuse to speak at all. Unlike bipolar adults, they flit rapidly between emotions; sometimes they seem to feel everything at once. At least 800,000 children in the United States have been diagnosed as bipolar, no doubt some of them wrongly. The disease is hard to pin down. The bipolar brain is miswired, but no one knows why it develops that way. There are many drugs, but it’s unclear how they work. Often, they don’t work at all, and they may interfere with normal brain growth. There are no studies on their long-term effects in children. Yet untreated bipolar disorder can be disastrous; 10 percent of sufferers commit suicide. Parents must choose between two wrenching options: treat their children and risk a bad outcome, or don’t treat and risk a worse one. No matter what they do, they are in for uncertainty and pain.

Amy knew none of this when Max was born. She did know new motherhood was tough. Max never slept through the night, and neither did she. He cried for hours at a time. He banged his head against his crib and screamed until his face burned red. Nursing, cuddling, pacifiers—none of them helped. At 2 a.m., at 3, at 4 and 5 and 6, Amy cradled her son, trying to believe this was typical infant irritability, the kind her friends with kids had warned her about. It must be colic or gas, she thought, as Max howled another day into being. Exhausted, mystified, she made jokes—he was born on Halloween, she ate too many spicy chicken wings before delivery—trying to explain how a baby too young to hold up his head could raise such hell.

After a year, the jokes gave way to worry. Max was reaching and surpassing his milestones, walking by 10 months and talking in sentences by age 1, but he wasn’t like the babies in parenting books. Richie carried his son to the backyard and tried to put him down, but Max shrank back in his father’s arms; he hated the feel of the grass beneath his small bare feet. Amy gave Max a bath and turned on the exhaust fan; he put his hands over his ears and screamed. At 13 months, he lined up dozens of Hot Wheels in the same direction, and when Amy nudged one out of order, he shrieked “like you’d just cut his arm off.” At day care, he terrorized his teachers and playmates. He wasn’t the biggest kid in the class, but he attacked without provocation or warning, biting hard enough to leave teeth marks. Every day, he hit and kicked and spat. Worries became guilt. Amy had been overweight and dehydrated in pregnancy. Was Max so explosive because she had done something wrong?

By 18 months, the day-care facility was threatening to throw Max out, and the Blakes were desperate. Richie, the drill sergeant, tried the strict discipline he’d grown up with—he said no, he withheld TV and dessert, he spanked. It didn’t work. Amy, the lawyer, tried bargaining with her toddler. That didn’t work either. Amy and Richie started to fight about how to raise their son. The family’s pediatrician had been treating kids for decades—he had once been Amy’s doctor—but he had no answers. All he could say was that this wasn’t the terrible twos come early. It was bigger than anything he could fix, and if the Blakes wanted help, they would have to look for it 20 miles down the road.

The Blakes started calling doctors in Boston. After three months of trying, they got through to Joseph Jankowski, chief of child psychiatry at Tufts-New England Medical Center, and scheduled an appointment for Nov. 18, just after Max’s 2nd birthday. Jankowski ran several lab tests, but they showed little except for slightly high levels of a metabolic enzyme. He ordered a brain scan and sat down with his interns to watch his new patient. Max behaved as usual: he screamed and bit Amy, then gathered up pieces of paper to draw on, only to rip them to shreds. After an hour, Jankowski said he thought Max might have bipolar disorder. He told the Blakes little else.

To the Blakes, bipolar disorder was as foreign as dengue fever. Amy had heard of “manic-depression,” but that was a serious illness, one that didn’t strike children. Although the National Institute of Mental Health (NIMH) estimates that 5.7 million American adults are affected by the disorder, most doctors, then as now, consider it impossible to diagnose in toddlers. There are still those who joke that every child is “bipolar”: up, down, at the mercy of emotion. Amy had her doubts as well. She sat in Jankowski’s office and wondered if she should get a second opinion. Worn down, she looked at the degrees on his wall, at the name embroidered on his white coat. “Well,” she thought, “I hope he knows what he’s talking about.”

Jankowski wanted to put Max on a low dose of Depakote, a drug used for seizures, migraines and bipolar disorder. Amy was used to migraine medications—she’d had the headaches for years—and she and some of her family members had taken antidepressants. Richie was more wary. Like many people, he didn’t think children should be on powerful psychoactive meds. He worried about side effects, a concern that would dog him and Amy for years to come. Max lasted on Depakote for just three weeks. He wasn’t eating and couldn’t sleep. Jankowski tried Zyprexa, an antipsychotic. Within days, Max started eating again. For the first time Amy could remember, he slept like the baby he was. “Good,” Amy thought. “We’ll keep him on this for a few weeks, like an antibiotic. Then he’ll get well and we’ll move on.”

On Feb. 4, Jankowski said he had a diagnosis. Amy was hoping for something with a cure—”something like a brain tumor, even, something we could read about and understand and fix.” Most likely, she thought, it would be attention-deficit/hyperactivity disorder; her friends’ kids all had that. Richie thought that whatever Max had, he might grow out of it, the way the hole in his heart had healed on its own. But Jankowski had little comfort for the Blakes. Their son’s problem was serious and incurable: a life sentence. Jankowski’s first impression had been borne out. Max was bipolar. Amy and Richie took their son home, and Amy started writing in a notebook that would become a complete log of Max’s medical history: “dx: Bipolar Disorder, Hyperactivity.” Then she closed the notebook. Max was screaming again. There was one good thing about this strange diagnosis, she thought: at least it meant she wasn’t a bad mother.

At the time, pediatric bipolar disorder was obscure, even within child psychiatry. Doctors at Massachusetts General Hospital (MGH) fully described the disorder just four years before Max’s diagnosis. In 1995, child psychiatrist Joseph Biederman and his protégée Janet Wozniak reported that 16 percent of the kids in their clinic had a form of the illness. “Back then it was considered so rare in children that you might see one in your entire career,” says Wozniak. “But we’d been blind to children who were right in front of us.” Doctors had missed the fact that their young patients were bouncing between pathological highs and lows, she says: if they saw kids on the upswing, they diagnosed hyperactivity, and if they saw the down side, they diagnosed depression. The MGH team’s ideas left many doctors skeptical, but other psychiatrists followed them closely.

Scientists now know that bipolar children have too much activity in a part of the brain called the amygdala, which regulates emotions, and not enough in the prefrontal cortex, the seat of rational thought. “They get so emotional that they can’t think,” says Mani Pavuluri, a child psychiatrist at the University of Illinois at Chicago. More than the rest of us, a bipolar child perceives the world as a dramatic and dangerous place. If he is shown a picture of a neutral face, he may see it as angry. Show him one that really is angry, and his prefrontal cortex will shut down while his amygdala lights up like a firecracker. The typical result: a fury that feeds on itself. Neurological research has its limits, though, and bipolar disorder still cannot be identified based on brain scans. Diagnosing it is more art than science. Many psychiatrists think that in the years since Max’s diagnosis, doctors have erred on the side of seeing it everywhere, mislabeling kids and creating a lucrative market for drug companies. Even one of Max’s docs says he thinks nine out of 10 kids with the bipolar label have been wrongly classified. But this sort of debate doesn’t much interest Amy. “I don’t care what diagnosis Max has,” she says. “To me, the concern is, what are we going to do about it?”

In the months after his diagnosis, Max’s med log filled up with drug after drug, but he didn’t get any better. His private day care kicked him out at 28 months, and the Blakes transferred him to their best remaining option, a public-school special education program. Now he was surrounded by children with physical or serious learning disabilities, in the care of people who were neither trained nor able to handle such a small, angry bull. Amy would drop him off in the morning, only to arrive at her Boston office and find a message from a teacher telling her to drive back to Peabody and pick him up. There were whole months when he was suspended and the Blakes were stuck at home. Something had to change.

Amy had never stopped thinking about a second opinion. Through a friend, she heard of Jean Frazier, a child psychiatrist at McLean Hospital in Belmont, Mass., who was interested in behavioral therapies as well as drugs. On Dec. 19, 2000—a year, a month and a day after Max’s first visit with Jankowski—the Blakes took their 3-year-old to Frazier’s office. Max started off in good spirits, but as the appointment wore on, he began to fidget. He refused to look at Frazier when she asked him questions. He tried to bite Richie. He told Amy he wanted to go home. Instead, the Blakes stayed, and Frazier started asking questions again, this time in a whisper. Now Max paid attention, and Frazier realized something: he had been irritated by the sound of her voice. Max couldn’t tolerate normal volumes of speech. In her notes, she wrote that he was “a handsome young man with dark hair and a twinkle in his eye.” She agreed that he had classic symptoms of bipolar disorder, but she ordered a fresh round of brain scans and blood tests. She told the Blakes she wanted to streamline some of Max’s meds. They asked about play therapy, which Jankowski had discouraged. She gave them a referral. More important, she gave them hope.

Max was still adrift in the public schools’ special-ed program, and soon he would need to go to kindergarten. Under state and federal disability laws, the district had to pay for him to attend private school if it couldn’t meet his needs. Hoping to keep Max in the public-school system, Peabody administrators designed a special curriculum for him. He lasted six weeks, punching and cursing and vandalizing the walls, before they gave up and agreed to send him to the Manville School, part of the Judge Baker Children’s Center in Boston, at a cost of $64,000 a year. Manville looked like a regular school, with desks and chairs and a brightly colored mural in the lobby, but it was staffed by social workers and psychologists. It had three teachers for every eight students and almost as many timeout rooms as classrooms. Amy bought a huge three-ring binder where she kept every teacher’s note about her son’s school-day behavior, the way another mother might save book reports and drawings of dinosaurs. She also found a babysitter, Jenny Mellor, who could watch Max in the afternoons. Richie arranged to spend more time at home, too. He became a firefighter; he had to sleep at the firehouse two nights a week, but that meant he could spend the following days with his son.

For all the support he was getting, Max’s life was still a series of upheavals. In the space of one year, he tried eight psychoactive medications. Despite all the meds—and in part, because of them—he was an emotional wreck. Amy learned to recognize a look in his eyes. When she saw it, she’d think, “Here comes the devil.” In January 2002, 4-year-old Max said he wanted to “freeze to death.” In June, he ran away; Amy found him hiding under a neighbor’s car. Max seemed to think his imaginary friends were real. His parents wondered if he was hearing voices. In the grocery store, he heard a woman laughing in the next aisle and broke down—he thought she was laughing at him.

By now, Amy and Richie were feeling stranded. Max couldn’t go to birthday parties, so Amy quietly tossed the invitations in the trash. Some of the Blakes’ friends stopped calling. Amy’s mother started e-mailing her “cures” for bipolar disorder she’d found on the Web. Amy wondered if Max’s own relatives thought he was “damaged goods.” Strangers were no more understanding. One afternoon at the mall, Max threw a fit, and a woman walked up to Amy and told her people like her shouldn’t be allowed to have children.

Even at home, Amy and Richie weren’t safe from judgment. At their most strained, they turned on each other. Richie had been a patient person before Max came along, but now his patience was worn “as thin as a sheet of paper.” Bipolar disorder runs strongly in families, so in the heat of their arguments, Amy and Richie both yelled the worst thing they could think of: “He’s your kid! It’s your fault!”

The Blakes had always planned on having another child. During the times when Max was stable—and there were some—Amy found herself thinking about that second baby. She and Richie feared their own genes now, but maybe they could adopt. She started looking at agencies. The next day, Max threw a tantrum, as if to announce that he knew what she was up to. That was when the Blakes decided their first child would be their last. Later, Max started to ask why he didn’t have any siblings. At times, Amy said she didn’t want him to have to share his toys, or that “Mommy and Daddy wanted one perfect child, and we got him.” There were other times when her patience, like Richie’s, was thin, and she felt that Max was sturdy enough to take a joke. Those were the times when she answered his question. “Look in the mirror,” she’d say, half-smiling. “That’s why.”

By 7½, Max was on so many different drugs that Frazier and his parents could no longer tell if they were helping or hurting him. He was suffering from tics, blinking his eyes, clearing his throat and “pulling his clothes like he wanted to get out of his skin,” says Richie. In February 2005, under Frazier’s supervision, the Blakes took Max off all his meds. With the chemicals out of his system, Max was not the same child he had been at 2. He was worse. Bipolar disorder often gets more serious with age. The brain also reacts to some drugs by remodeling itself, and its dopamine receptors end up naked and sensitive. When the drugs are removed, it’s a shock. Off his meds, Max became delusional and paranoid. He imagined Amy was poisoning him and refused to eat anything she cooked. He talked about death constantly and slept little more than two hours a night. Within a month Frazier had put him back on medication, but with a caveat: she wanted to place him in a short-term bed in a child psych ward.

This move did not sit well with the Blakes. They visited Max every day in the hospital but were disturbed to find that many parents with kids on the ward didn’t do likewise. They also worried that Max wasn’t getting proper treatment. Doctors couldn’t check his med levels because he wouldn’t sit still for blood tests. Finally, after three weeks, Amy and Richie held him down, and the resulting test showed his levels of lithium were indeed too low to do any good. Against Frazier’s advice, they pulled Max out of the hospital and vowed never to send him away again. Two months later he jumped out his bedroom window.

Today, Max’s med log is jammed full of papers: prescription sheets, printouts from Web sites, business cards from doctors. At 10, he has been on 38 different psychoactive drugs. The meds have serious side effects. They have made Max gain weight, and because he’s still growing, they frequently need to be changed. The Blakes are aware that many people think their child—any child—should not be on so many drugs. They aren’t always happy about it either. But to some degree, they have made their peace with medication.

Max’s prognosis has also grown more complex in the seven and a half years since Jankowski first labeled him as bipolar and hyperactive. “He’s oppositional defiant, he’s dyslexic, he’s ADHD, he’s OCD,” says Amy. “Give me an initial and he has it.” Bipolar children, especially those diagnosed early, often have such a litany of disorders. The bipolar brain tries to compensate for its weak prefrontal cortex by roping in other areas to help; these areas may now become dysfunctional, too. Child psychiatrists thus face an enormous practical challenge: they often can’t treat one disorder without affecting another one. “It’s like a balloon where you push on one side and the other side pops out,” says Wozniak, the MGH psychiatrist who helped define childhood bipolar disorder. With kids like Max, she adds, parents often have to settle for “just having one part of the symptoms reduced.”

Max’s life has improved in some ways since his early childhood. Manville has given him a social life. He still has violent tantrums at school, but he also has a best friend, a sweet blond boy with a mild anxiety disorder. Last year he won a “Welcome Wagon” award after teachers noticed he was always the first to show new students around. When his classmates have outbursts of their own, he talks them down. “He’ll say that maybe they need to take some space, take a deep breath, leave the classroom,” says his teacher, Julie Higgins. He has not, however, figured out how to talk himself down, and for all he has progressed as a classmate, he struggles as a student. Technically, Max is in fourth grade—Manville does not separate grade levels—but he is behind in some subjects. He loves science and art, but he has a hard time reading, and although he is creative, he can’t put his ideas in a coherent order. Even holding a pencil for more than a few minutes can be a challenge. “Sometimes you can look at him and you know his disorder has captured him,” says the school’s director, Jim Prince. “But we can’t abandon him. We have to be able to hold on to him, sometimes literally, but also emotionally, to help him come out on the other side.”

Max also finds it hard to describe his feelings, deep and strong though they are. Jean Frazier, now at Cambridge (Mass.) Health Alliance, has him sketch his worries on a whiteboard. At a recent appointment Max drew a crab: insomnia was making him “crabby.” His other therapist, Stuart Ablon, a clinical psychologist at MGH, tries to reach him through play. Max brings Power Ranger action figures to his sessions. “He likes to demonstrate with the characters that there is good and evil, and evil usually triumphs,” Ablon says. “He is greatly worried that the evil parts of himself will always get the better of his good side. But you can’t ask him about that directly. It’s too raw.” Once, Ablon tried. Max whipped a toy at him, cutting his leg. “As soon as I started to bleed,” Ablon says, “he felt ashamed and shut down.”

Max’s feelings often move faster than his thoughts. Riding home after he wrote his most recent suicide note, he sobbed, “Please don’t send me to the hospital.” By the time he had walked through the door he was indignant: he had written the note because his teacher had “treated him unfairly as pre-usual,” he said, sending him to timeout. Then he was ashamed for getting in trouble in the first place. “I was scared of disappointing you and Dad because I didn’t finish the day at school,” he told Amy, knitting his fingers together. “I was sad and scared. I felt like everyone was out to get me.” A minute later he was laughing, romping with the family’s pet bull mastiff as if he’d never been scared of anything.

Team sports are out of the question; Max is too volatile. But he is learning self-control through therapeutic horseback riding at Challenge Unlimited in Andover, Mass. “We have to teach kids like him to relax,” his instructor, Linda Goss, said one recent afternoon as Max rode around an indoor ring. “The trick is to give him choices while also giving him clear directions. He gets a little frustrated, and the horse picks up on that.” On cue, Max’s horse galloped toward a pair of jumping poles that weren’t set up yet. Linda ran, telling him not to jump, but it was too late. The horse made the leap. “I’m sorry,” Max said. “I don’t have control.” But he stayed on long enough to do a few fancy tricks. Last year he won two bronze medals in the state Special Olympics. He wore them for weeks and wanted to keep them on in the shower.

Karate is helping with his self-esteem, although there have been bumps along the way. At a dojo he used to attend, a teacher tried to toughen him up by calling him a crybaby, and Max quit on the spot. Five months ago he restarted karate at Cervizzi’s Martial Arts Academy in North Reading, Mass., which makes a point of accommodating special-needs kids. He has already earned his yellow belt. “Sometimes he just assumes he’s wrong when he isn’t,” says Kris Smith, his sensei. “He may need extra encouragement at times. But he knows the blocks, kicks and punches.”

It is strange to hear that Max Blake is punching and kicking, phrased as if it’s a good thing. He has never acted out in karate class, but he still attacks the people he loves. Jenny Mellor, his babysitter, had a son of her own three years ago, and when she comes over, she brings little Jackson with her. Max is almost always gentle with him. Almost. Last summer, the three of them went swimming in the Blakes’ backyard pool, and Jenny found a dead rodent in the filter. Max had heard a lot about rabies at school, and he tore out of the water. Jenny and Jackson kept swimming. Max got angry, hyperventilating and screaming over and over, “Nobody listens to me!” Eventually Jenny became alarmed. She climbed out, went inside and locked herself and her toddler in the family’s home office. Max charged the door, shattering a mirror hung on the back of it. Jenny sat behind the locked door, shaking, and dialed a neighbor for help. She was scared for herself and her son, but, she says, she was “crying for Max.” She very nearly quit. But she came back two weeks later, and she has been coming back ever since.

Amy is still figuring out how best to discipline her son. He needs boundaries, but she admits she’s a sucker. She used to reward his good behavior with toys, and it seemed to work until she realized it was bribery and also that it was about to bankrupt her. “I started to feel like I had a Toys ‘R’ Us annex in my house,” she says. So, with Ablon’s guidance, she is trying to learn a new way to raise Max, using techniques outlined in the book “Treating Explosive Kids.” Richie hasn’t read the book. He has too much Marine in him to apply its methods, which focus on the child’s concerns and discourage parents from imposing their will. When he was growing up, he says, a kid like Max would have gotten “smacked around a little. Not everybody was touchy-feely and politically correct.” He admits he sometimes eggs Max on. “I’m trying to teach him in my own way,” he says. It has been tough for Richie to accept that his son is not like other people’s sons. “When I was Max’s age, I was playing hockey and baseball. I was athletic,” he says. “Max is 10 years old and he can’t ride a bicycle, and that bums me out. He can’t do a lot of things kids his age can do. But maybe as he gets older—you know, Tom Brady didn’t start playing football until he was 12. There’s still hope.”

Richie comes from a long line of stoics. There is mental illness in his family tree, but it is not discussed. His brother took his own life at 21; no one knows why. “My father’s not going to talk to me about it,” says Richie, “because that’s the way he is—he doesn’t talk about anything.” Like his father, Richie is no fan of talking. He also wrestles with some of the same issues as his son: he has a temper, and Amy calls him “inflexible.” Richie counters that he’s “stern, and she’s Caspar Milquetoast.” He says he has never been to therapy. But late last year, Amy demanded that the two of them see a marriage counselor. Richie agreed. They went a few times, but there were “scheduling issues,” says Richie, and they haven’t gone back. For the moment, they are getting help from the same people who help Max. Anything that makes his life easier makes theirs easier, too.

Max’s life, of course, is rarely easy. During a recent appointment at Frazier’s office, he went into full-fledged mania. Laughing wildly, he rolled on the floor, then crawled over to his parents and grabbed an empty medication bottle, yelling, “Drugs! I’ve got drugs! It’s child safety!” Richie grabbed it back, Max screamed, Richie threw the bottle across the room, as if playing fetch. Max squealed and dove for it, then began to sing into the neck of the bottle: “Booorn to be wiiiiild …” Amy rolled her eyes: “Two kids.” And then: “It’s hard not to laugh.”

It was. And it was hard to look at Max, who has borne so much, and remember that the grin on his face was not a sign of childish goofiness but a symptom of an illness. Sadness and anger can be pathological; anyone can see that. It’s harder to see happiness that way. As Amy guided Max out of the office, she asked him if he was OK. Max cocked his head. It took him a few seconds to come up with his answer: “Apparently, yes.” On this rare occasion, he’d described himself perfectly.

Max will never truly be OK. In a few years, he will hit puberty, and at that point things will get even more complicated. Teenage rebellion is one thing; a bipolar teenager’s rebellion can end in tragedy. “What happens the first time he says to me, ‘I’m not taking my pills’?” says Amy. “I can’t put them down his throat.” She also worries about the end of 10th grade, which is as far as the Manville School goes. Amy doesn’t think Max will go back to public school in Peabody, which means he’ll have to find another special school or he’ll never go to college. Max hasn’t processed that yet; he wants to be an animator and has already set his sights on the Massachusetts College of Art and Design. Amy hasn’t really processed it either. Every year she puts money in a college account, although she knows the money almost certainly won’t be used for tuition. “I want to believe that Max will have this great normal life, but I don’t know what’s going to happen,” she says. “I wouldn’t be able to get up in the morning if I thought about it. So I don’t anymore.”

There are scientists who have thought about the future of children like Max in great depth. Many still think bipolar disorder is vastly overdiagnosed, but they agree that those who have it face a long, rough road. Two years ago the NIMH released findings from a large study of kids diagnosed between 7 and 17. The ones who fared badly had an early onset of the disorder, as well as psychosis, anxiety, ADHD and a tendency to switch quickly between mania and depression. Max has all these. His chances do not look good.

For now, though, his 18th birthday is a long way off. The Blakes are focusing on making it to his 11th. They have found things to look forward to. “We have Max for better or worse, and there’s a lot of worse, but there’s a lot of better, too,” Amy says. “I’m really lucky because I have a kid who can hug me and tell me he loves me, and there are a lot of autistic kids at Manville whose parents never get that. Through all the tears and the hitting and the ‘I hate you,’ I get to hear ‘I love you’.”

There was a night last month when Max was calm, and after he finished his homework, he curled up in an easy chair with Amy. She was reading him a book, and although it was only 7:45 his eyelids were fluttering. Eventually he began to whine, and Amy asked him if he was about to start a fight. “Probably,” he said. “Let’s just get it over with.” But he didn’t fight. Instead, he was quiet for a few minutes, then he looked at her and said, “Your heart is the size of the world.” What he may not realize now, although he surely will someday, is that it has to be.

Right now, somewhere in the world—in a petri dish in Baltimore, maybe, or in the salivary glands of a laboratory-bred mosquito in Seattle, or in the bloodstream of a villager in Ghana—resides a chemical compound that could help eradicate human history’s biggest killer. Scientists have many promising malaria vaccine candidates in the works, and for the first time one has reached advanced human trials. If it or another candidate is even partly effective in people, it could save the lives of millions of children and pregnant women. It would be the only vaccine yet developed against a human parasite, an achievement of Nobel caliber. And it could, in its first-generation form, be distributed in Africa as soon as 2015.

“If all goes well, five years from today, a vaccine could start being implemented in a wide way in six- to 12-week-old children,” says Joe Cohen, a scientist who is leading some of the most promising research. “It is a fantastic achievement. We are all very proud of that.” This is an extraordinary moment for malaria vaccine research. So why isn’t Regina Rabinovich singing from the rooftops?