# data[].attributes.body
Medical Consent

# data[].attributes.attachment_link.readable_text
Imagine waking up after a serious accident to discover you've become an unwitting subject in a medical study without ever agreeing to participate.

It's a controversial reality of emergency research, and now concern is growing that dwindling research budgets are making it harder to alert the community about the studies so people can decide ahead of time whether to opt in or out.

A case in point: a Department of Defense-sponsored study led by the University of Pittsburgh, which is currently testing the practice of giving bleeding patients plasma to help their blood clot during flights to the hospital. Each of six sites gets $20,000 out of a total $6.5 million budget for community awareness efforts such as sending out letters and paying for radio spots. People are told if they don't want to take part in the research, they can get a free bracelet to wear at all times, letting emergency workers know their wishes.

Though millions of people could potentially be trauma victims at the various sites, only 300 people at one site - members of a Jehovah's Witness congregation in Louisville - have asked for bracelets. Researchers say this meager response shows the notification has reached far too few people.

"Certainly you would like to reach everyone. But there's no way," says Laura Trachtenberg, research coordinator at the University of Louisville. "So if you do the due diligence, you've done the best you can. It's very challenging."

Fellow researcher Clifton Callaway, a professor of emergency medicine at the University of Pittsburgh, says it would be a lot easier with more research dollars. A January study in the Journal of the American Medical Association found U.S. funding for medical research overall increased 6% a year from 1994 to 2004, then slowed dramatically to 0.8% a year through 2012.

Helicopters similar to this Air Methods Kentucky medical chopper ferry patients to the University of Louisville hospital for a clinical trial in which bleeding patients get plasma during their flights. Because they are incapacitated, they cannot provide informed consent, raising numerous ethical issues. (Photo: Air Methods Kentucky)

With drug companies spending an estimated $2.5 billion annually on advertising to consumers, "the average person is much more likely to hear about (the fibromyalgia drug) Lyrica or something," Callaway says. "One ad costs more than the entire research budget of a trial like ours."

But Lynne Richardson, a professor of emergency medicine at the Icahn School of Medicine at New York's Mount Sinai who researches community notification, says money matters less than reaching out to potential subjects in an effective way. She says most people who learn about such studies are OK with participating, and a mechanism for opting out isn't required by the federal government.

Plus, she says, "no matter how much money you spend, some people aren't going to pay attention."
Research without consent
Informed consent is rooted in the Nuremberg code of 1947, drafted in the wake of Nazi experimentation. Exception-from-consent studies are rare; Richardson estimates there are about six large national trials and a handful of small studies currently enrolling people. They are allowed only when patients or their families can't possibly give their permission, such as when someone is alone and unconscious.

Arthur Caplan, head of the division of medical ethics at New York University's Langone Medical Center, says research without consent "absolutely should be the last resort."

It's highly regulated. The U.S. Food and Drug Administration has a special rule requiring, among other things, that patients are in life-threatening situations and that currently-available treatments are unproven or unsatisfactory. Researchers must apply to institutional review boards for waivers, be closely monitored and report any problems.

Caplan says the trials are designed to find better ways to save lives in emergencies and can be stopped when initial results show outcomes are the same or worse. Callaway says he has been involved in more than one cardiac arrest study stopped because it showed no clear benefit.

Some studies actually have harmed patients. A 2008 JAMA review of 16 clinical trials showed blood substitutes, including some tested without consent, were associated with "a significantly increased risk" of heart attacks and death.

Callaway says it's too early to know what his current four-year plasma study will find, but no problems or deaths have been attributed to the study so far. Researchers point out that giving plasma isn't a new practice; surgeons at trauma centers now may give plasma in the hospital. The study aims to find out if giving it in transport helicopters instead reduces the chance of death or severe complications.

A similar no-consent study in Denver, also sponsored by the defense department, tests giving another plasma product with slightly lower levels of clotting proteins during ambulance rides. And a third study in Maryland tests administering cold fluid to lower body temperature in bleeding patients to buy time for resuscitation.

Callaway says such studies "are definitely worth it" given what researchers can learn. Rosamond Rhodes, director of bioethics education at Mount Sinai, agrees.

But Caplan says while the research can lead to breakthroughs, there's always a chance of hurting unwitting subjects, and "that's the gamble (the nation) took when we allowed this sort of research to proceed."
Buying in, opting out
Ethicists say that gamble makes FDA-required community awareness all the more important.

The first step is community consultation, which happens before the study is launched and can determine whether it takes place in a certain location at all.

Richardson says effective consultation involves soliciting opinions from area leaders and also reaching out to groups most likely to be affected, which in the case of blood-related studies include Jehovah's Witnesses, who believe blood transfusions are forbidden.

"Public notification" or "public disclosure" involves telling the public what's happening through media such as radio, brochures or the Internet - and letting them know about opt-out methods like bracelets.

Richardson currently is studying the best ways to reach those most likely to be affected. As far as opting out, she says people who do so often oppose being a part of any research or have had bad experiences with the hospital involved.

Some ethicists argue that opting out is an important choice and say public notification often isn't up to par. "I don't see (community outreach) happening quite that aggressively," Caplan says.

That's because of the limited resources, researchers say. In Louisville, for example, researchers couldn't afford television spots or newspaper ads; half their awareness budget went to radio spots and the other half went to develop a website and fund printing and postage for the letter sent to Jehovah's Witness congregations.

"We did the best we could," says Brian Harbrecht, who heads up the plasma study there.

Rhodes acknowledges public notification could be done better but says it's an open question whether more of the limited research dollars should be diverted away from the studies themselves.

Such questions need to be answered, researchers and ethicists say, because the stakes are high: They are expecting people to unknowingly accept risk to advance medical science.

"Everyone's well aware you're experimenting without permission," Caplan says. But with emergency research, "I realistically trust there's no other way."

Read or Share this story: http://usat.ly/1HPxMQE

# data[].attributes.attachment_link.title
No-consent medical experiments put ethics to test

# data[].attributes.attachment_link.description
Imagine waking up after a serious accident to discover you've become an unwitting subject in a medical study without ever agreeing to participate. It's a controversial reality of emergency research, and now concern is growing that dwindling research budgets are making it harder to alert the community about the studies so people can decide ahead of time whether to opt in or out.

# data[].attributes.attachment_link.readable_text
Much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong. So why are doctors-to a striking extent-still drawing upon misinformation in their everyday practice? Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science.

In 2001, rumors were circulating in Greek hospitals that surgery residents, eager to rack up scalpel time, were falsely diagnosing hapless Albanian immigrants with appendicitis. At the University of Ioannina medical school's teaching hospital, a newly minted doctor named Athina Tatsioni was discussing the rumors with colleagues when a professor who had overheard asked her if she'd like to try to prove whether they were true-he seemed to be almost daring her. She accepted the challenge and, with the professor's and other colleagues' help, eventually produced a formal study showing that, for whatever reason, the appendices removed from patients with Albanian names in six Greek hospitals were more than three times as likely to be perfectly healthy as those removed from patients with Greek names. "It was hard to find a journal willing to publish it, but we did," recalls Tatsioni. "I also discovered that I really liked research." Good thing, because the study had actually been a sort of audition. The professor, it turned out, had been putting together a team of exceptionally brash and curious young clinicians and Ph.D.s to join him in tackling an unusual and controversial agenda.

Last spring, I sat in on one of the team's weekly meetings on the medical school's campus, which is plunked crazily across a series of sharp hills. The building in which we met, like most at the school, had the look of a barracks and was festooned with political graffiti. But the group convened in a spacious conference room that would have been at home at a Silicon Valley start-up. Sprawled around a large table were Tatsioni and eight other youngish Greek researchers and physicians who, in contrast to the pasty younger staff frequently seen in U.S. hospitals, looked like the casually glamorous cast of a television medical drama. The professor, a dapper and soft-spoken man named John Ioannidis, loosely presided.

One of the researchers, a biostatistician named Georgia Salanti, fired up a laptop and projector and started to take the group through a study she and a few colleagues were completing that asked this question: were drug companies manipulating published research to make their drugs look good? Salanti ticked off data that seemed to indicate they were, but the other team members almost immediately started interrupting. One noted that Salanti's study didn't address the fact that drug-company research wasn't measuring critically important "hard" outcomes for patients, such as survival versus death, and instead tended to measure "softer" outcomes, such as self-reported symptoms ("my chest doesn't hurt as much today"). Another pointed out that Salanti's study ignored the fact that when drug-company data seemed to show patients' health improving, the data often failed to show that the drug was responsible, or that the improvement was more than marginal.

Salanti remained poised, as if the grilling were par for the course, and gamely acknowledged that the suggestions were all good-but a single study can't prove everything, she said. Just as I was getting the sense that the data in drug studies were endlessly malleable, Ioannidis, who had mostly been listening, delivered what felt like a coup de grâce: wasn't it possible, he asked, that drug companies were carefully selecting the topics of their studies-for example, comparing their new drugs against those already known to be inferior to others on the market-so that they were ahead of the game even before the data juggling began? "Maybe sometimes it's the questions that are biased, not the answers," he said, flashing a friendly smile. Everyone nodded. Though the results of drug studies often make newspaper headlines, you have to wonder whether they prove anything at all. Indeed, given the breadth of the potential problems raised at the meeting, can any medical-research studies be trusted?

That question has been central to Ioannidis's career. He's what's known as a meta-researcher, and he's become one of the world's foremost experts on the credibility of medical research. He and his team have shown, again and again, and in many different ways, that much of what biomedical researchers conclude in published studies-conclusions that doctors keep in mind when they prescribe antibiotics or blood-pressure medication, or when they advise us to consume more fiber or less meat, or when they recommend surgery for heart disease or back pain-is misleading, exaggerated, and often flat-out wrong. He charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His work has been widely accepted by the medical community; it has been published in the field's top journals, where it is heavily cited; and he is a big draw at conferences. Given this exposure, and the fact that his work broadly targets everyone else's work in medicine, as well as everything that physicians do and all the health advice we get, Ioannidis may be one of the most influential scientists alive. Yet for all his influence, he worries that the field of medical research is so pervasively flawed, and so riddled with conflicts of interest, that it might be chronically resistant to change-or even to publicly admitting that there's a problem.

For starters, he explains, the odds are that in any large database of many nutritional and health factors, there will be a few apparent connections that are in fact merely flukes, not real health effects-it's a bit like combing through long, random strings of letters and claiming there's an important message in any words that happen to turn up. But even if a study managed to highlight a genuine health connection to some nutrient, you're unlikely to benefit much from taking more of it, because we consume thousands of nutrients that act together as a sort of network, and changing intake of just one of them is bound to cause ripples throughout the network that are far too complex for these studies to detect, and that may be as likely to harm you as help you. Even if changing that one factor does bring on the claimed improvement, there's still a good chance that it won't do you much good in the long run, because these studies rarely go on long enough to track the decades-long course of disease and ultimately death. Instead, they track easily measurable health "markers" such as cholesterol levels, blood pressure, and blood-sugar levels, and meta-experts have shown that changes in these markers often don't correlate as well with long-term health as we have been led to believe.

On the relatively rare occasions when a study does go on long enough to track mortality, the findings frequently upend those of the shorter studies. (For example, though the vast majority of studies of overweight individuals link excess weight to ill health, the longest of them haven't convincingly shown that overweight people are likely to die sooner, and a few of them have seemingly demonstrated that moderately overweight people are likely to live longer.) And these problems are aside from ubiquitous measurement errors (for example, people habitually misreport their diets in studies), routine misanalysis (researchers rely on complex software capable of juggling results in ways they don't always understand), and the less common, but serious, problem of outright fraud (which has been revealed, in confidential surveys, to be much more widespread than scientists like to acknowledge).

If a study somehow avoids every one of these problems and finds a real connection to long-term changes in health, you're still not guaranteed to benefit, because studies report average results that typically represent a vast range of individual outcomes. Should you be among the lucky minority that stands to benefit, don't expect a noticeable improvement in your health, because studies usually detect only modest effects that merely tend to whittle your chances of succumbing to a particular disease from small to somewhat smaller. "The odds that anything useful will survive from any of these studies are poor," says Ioannidis-dismissing in a breath a good chunk of the research into which we sink about $100 billion a year in the United States alone.

Most journal editors don't even claim to protect against the problems that plague these studies. University and government research overseers rarely step in to directly enforce research quality, and when they do, the science community goes ballistic over the outside interference. The ultimate protection against research error and bias is supposed to come from the way scientists constantly retest each other's results-except they don't. Only the most prominent findings are likely to be put to the test, because there's likely to be publication payoff in firming up the proof, or contradicting it.

But even for medicine's most influential studies, the evidence sometimes remains surprisingly narrow. Of those 45 super-cited studies that Ioannidis focused on, 11 had never been retested. Perhaps worse, Ioannidis found that even when a research error is outed, it typically persists for years or even decades. He looked at three prominent health studies from the 1980s and 1990s that were each later soundly refuted, and discovered that researchers continued to cite the original results as correct more often than as flawed-in one case for at least 12 years after the results were discredited.

Doctors may notice that their patients don't seem to fare as well with certain treatments as the literature would lead them to expect, but the field is appropriately conditioned to subjugate such anecdotal evidence to study findings. Yet much, perhaps even most, of what doctors do has never been formally put to the test in credible studies, given that the need to do so became obvious to the field only in the 1990s, leaving it playing catch-up with a century or more of non-evidence-based medicine, and contributing to Ioannidis's shockingly high estimate of the degree to which medical knowledge is flawed. That we're not routinely made seriously ill by this shortfall, he argues, is due largely to the fact that most medical interventions and advice don't address life-and-death situations, but rather aim to leave us marginally healthier or less unhealthy, so we usually neither gain nor risk all that much.

Medical research is not especially plagued with wrongness. Other meta-research experts have confirmed that similar issues distort research in all fields of science, from physics to economics (where the highly regarded economists J. Bradford DeLong and Kevin Lang once showed how a remarkably consistent paucity of strong evidence in published economics studies made it unlikely that any of them were right). And needless to say, things only get worse when it comes to the pop expertise that endlessly spews at us from diet, relationship, investment, and parenting gurus and pundits. But we expect more of scientists, and especially of medical scientists, given that we believe we are staking our lives on their results. The public hardly recognizes how bad a bet this is. The medical community itself might still be largely oblivious to the scope of the problem, if Ioannidis hadn't forced a confrontation when he published his studies in 2005.

Ioannidis initially thought the community might come out fighting. Instead, it seemed relieved, as if it had been guiltily waiting for someone to blow the whistle, and eager to hear more. David Gorski, a surgeon and researcher at Detroit's Barbara Ann Karmanos Cancer Institute, noted in his prominent medical blog that when he presented Ioannidis's paper on highly cited research at a professional meeting, "not a single one of my surgical colleagues was the least bit surprised or disturbed by its findings." Ioannidis offers a theory for the relatively calm reception. "I think that people didn't feel I was only trying to provoke them, because I showed that it was a community problem, instead of pointing fingers at individual examples of bad research," he says. In a sense, he gave scientists an opportunity to cluck about the wrongness without having to acknowledge that they themselves succumb to it-it was something everyone else did.

To say that Ioannidis's work has been embraced would be an understatement. His PLoS Medicine paper is the most downloaded in the journal's history, and it's not even Ioannidis's most-cited work-that would be a paper he published in Nature Genetics on the problems with gene-link studies. Other researchers are eager to work with him: he has published papers with 1,328 different co-authors at 538 institutions in 43 countries, he says. Last year he received, by his estimate, invitations to speak at 1,000 conferences and institutions around the world, and he was accepting an average of about five invitations a month until a case last year of excessive-travel-induced vertigo led him to cut back. Even so, in the weeks before I visited him he had addressed an AIDS conference in San Francisco, the European Society for Clinical Investigation, Harvard's School of Public Health, and the medical schools at Stanford and Tufts.

The irony of his having achieved this sort of success by accusing the medical-research community of chasing after success is not lost on him, and he notes that it ought to raise the question of whether he himself might be pumping up his findings. "If I did a study and the results showed that in fact there wasn't really much bias in research, would I be willing to publish it?" he asks. "That would create a real psychological conflict for me." But his bigger worry, he says, is that while his fellow researchers seem to be getting the message, he hasn't necessarily forced anyone to do a better job. He fears he won't in the end have done much to improve anyone's health. "There may not be fierce objections to what I'm saying," he explains. "But it's difficult to change the way that everyday doctors, patients, and healthy people think and behave."

As helter-skelter as the University of Ioannina Medical School campus looks, the hospital abutting it looks reassuringly stolid. Athina Tatsioni has offered to take me on a tour of the facility, but we make it only as far as the entrance when she is greeted-accosted, really-by a worried-looking older woman. Tatsioni, normally a bit reserved, is warm and animated with the woman, and the two have a brief but intense conversation before embracing and saying goodbye. Tatsioni explains to me that the woman and her husband were patients of hers years ago; now the husband has been admitted to the hospital with abdominal pains, and Tatsioni has promised she'll stop by his room later to say hello. Recalling the appendicitis story, I prod a bit, and she confesses she plans to do her own exam. She needs to be circumspect, though, so she won't appear to be second-guessing the other doctors.

Tatsioni doesn't so much fear that someone will carve out the man's healthy appendix. Rather, she's concerned that, like many patients, he'll end up with prescriptions for multiple drugs that will do little to help him, and may well harm him. "Usually what happens is that the doctor will ask for a suite of biochemical tests-liver fat, pancreas function, and so on," she tells me. "The tests could turn up something, but they're probably irrelevant. Just having a good talk with the patient and getting a close history is much more likely to tell me what's wrong." Of course, the doctors have all been trained to order these tests, she notes, and doing so is a lot quicker than a long bedside chat. They're also trained to ply the patient with whatever drugs might help whack any errant test numbers back into line. What they're not trained to do is to go back and look at the research papers that helped make these drugs the standard of care. "When you look the papers up, you often find the drugs didn't even work better than a placebo. And no one tested how they worked in combination with the other drugs," she says. "Just taking the patient off everything can improve their health right away." But not only is checking out the research another time-consuming task, patients often don't even like it when they're taken off their drugs, she explains; they find their prescriptions reassuring.

Later, Ioannidis tells me he makes a point of having several clinicians on his team. "Researchers and physicians often don't understand each other; they speak different languages," he says. Knowing that some of his researchers are spending more than half their time seeing patients makes him feel the team is better positioned to bridge that gap; their experience informs the team's research with firsthand knowledge, and helps the team shape its papers in a way more likely to hit home with physicians. It's not that he envisions doctors making all their decisions based solely on solid evidence-there's simply too much complexity in patient treatment to pin down every situation with a great study. "Doctors need to rely on instinct and judgment to make choices," he says. "But these choices should be as informed as possible by the evidence. And if the evidence isn't good, doctors should know that, too. And so should patients."

In fact, the question of whether the problems with medical research should be broadcast to the public is a sticky one in the meta-research community. Already feeling that they're fighting to keep patients from turning to alternative medical treatments such as homeopathy, or misdiagnosing themselves on the Internet, or simply neglecting medical treatment altogether, many researchers and physicians aren't eager to provide even more reason to be skeptical of what doctors do-not to mention how public disenchantment with medicine could affect research funding. Ioannidis dismisses these concerns. "If we don't tell the public about these problems, then we're no better than nonscientists who falsely claim they can heal," he says. "If the drugs don't work and we're not sure how to treat something, why should we claim differently? Some fear that there may be less funding because we stop claiming we can prove we have miraculous treatments. But if we can't really provide those miracles, how long will we be able to fool the public anyway? The scientific enterprise is probably the most fantastic achievement in human history, but that doesn't mean we have a right to overstate what we're accomplishing."

We could solve much of the wrongness problem, Ioannidis says, if the world simply stopped expecting scientists to be right. That's because being wrong in science is fine, and even necessary-as long as scientists recognize that they blew it, report their mistake openly instead of disguising it as a success, and then move on to the next thing, until they come up with the very occasional genuine breakthrough. But as long as careers remain contingent on producing a stream of research that's dressed up to seem more right than it is, scientists will keep delivering exactly that.

"Science is a noble endeavor, but it's also a low-yield endeavor," he says. "I'm not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact."

We want to hear what you think about this article. Submit a letter to the editor or write to letters@theatlantic.com.

# data[].attributes.attachment_link.description
Much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong. So why are doctors-to a striking extent-still drawing upon misinformation in their everyday practice? Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science.

# data[].attributes.attachment_link.title
The immortal cells of Henrietta Lacks - Robin Bulleri

# data[].attributes.attachment_link.readable_text
Have you ever heard of HeLa cells? They've been around for more than 60 years, but unless you're a medical researcher, the name probably didn't crop up on your radar until recently, if at all. In the past decade or so, countless articles -- and one New York Times bestselling book -- have been written about them.

But what's a HeLa cell? It's a line, or population, of cells, taken from a person and used in scientific research. Cell lines are often named after the people from whom they were originally derived, and HeLa comes from the first two letters in the name Henrietta Lacks. Cell lines are used in all kinds of ways, such as studying the effects of diseases or developing medications and vaccines, and play an invaluable role in medicine today.

But HeLa cells were the first -- the first line of human cells to survive in vitro (in a test tube). Named after a cancer patient, the cells were taken from Lacks' tissue samples and grown by a researcher named Dr. George Gey in 1951. Dr. Gey quickly realized that some of Lacks' cells were different from normal cells. While those died, they just kept on growing. After more than 50 years, there are now billions and billions of HeLa cells in laboratories all over the world. It's the most commonly used cell line, and it's known to be extremely resilient.

The fact that HeLa cells have been used in some very important, groundbreaking medical research is interesting enough, but there's another part of the story -- and that part is why Oprah might be making a movie about HeLa. Henrietta Lacks had no idea that her cells were taken and used in this way, and neither did her family. And while the cells became commercialized (researchers can buy a vial of them for $250) Lacks' family has lived without healthcare and in poverty. Henrietta Lacks' story isn't just about her contribution to medical research; it's about the ethics of biomedical research and the practice of informed consent. But let's start at the beginning, with Henrietta herself.

# data[].attributes.attachment_link.description
Have you ever heard of HeLa cells? They've been around for more than 60 years, but unless you're a medical researcher, the name probably didn't crop up on your radar until recently, if at all. In the past decade or so, countless articles -- and one New York Times bestselling book -- have been written about them.

# data[].attributes.attachment_link.readable_text
The Woman in the Photograph
There's a photo on my wall of a woman I've never met, its left corner torn and patched together with tape. She looks straight into the camera and smiles, hands on hips, dress suit neatly pressed, lips painted deep red. It's the late 1940s and she hasn't yet reached the age of thirty. Her light brown skin is smooth, her eyes still young and playful, oblivious to the tumor growing inside her - a tumor that would leave her five children motherless and change the future of medicine. Beneath the photo, a caption says her name is "Henrietta Lacks, Helen Lane or Helen Larson."

No one knows who took that picture, but it's appeared hundreds of times in magazines and science textbooks, on blogs and laboratory walls. She's usually identified as Helen Lane, but often she has no name at all. She's simply called HeLa, the code name given to the world's first immortal human cells - her cells, cut from her cervix just months before she died.

Her real name is Henrietta Lacks.

I've spent years staring at that photo, wondering what kind of life she led, what happened to her children, and what she'd think about cells from her cervix living on forever -bought, sold, packaged, and shipped by the trillions to laboratories around the world. I've tried to imagine how she'd feel knowing that her cells went up in the first space missions to see what would happen to human cells in zero gravity, or that they helped with some of the most important advances in medicine: the polio vaccine, chemotherapy, cloning, gene mapping, in vitro fertilization. I'm pretty sure that she - like most of us - would be shocked to hear that there are trillions more of her cells growing in laboratories now than there ever were in her body.

There's no way of knowing exactly how many of Henrietta's cells are alive today. One scientist estimates that if you could pile all HeLa cells ever grown onto a scale, they'd weigh more than 50 million metric tons - an inconceivable number, given that an individual cell weighs almost nothing. Another scientist calculated that if you could lay all HeLa cells ever grown end-to-end, they'd wrap around the Earth at least three times, spanning more than 350 million feet. In her prime, Henrietta herself stood only a bit over five feet tall.

I first learned about HeLa cells and the woman behind them in 1988, thirty-seven years after her death, when I was sixteen and sitting in a community college biology class. My instructor, Donald Defler, a gnomish balding man, paced at the front of the lecture hall and flipped on an overhead projector. He pointed to two diagrams that appeared on the wall behind him. They were schematics of the cell reproduction cycle, but to me they just looked like a neon-colored mess of arrows, squares, and circles with words I didn't understand, like "MPF Triggering a Chain Reaction of Protein Activations."

I was a kid who'd failed freshman year at the regular public high school because she never showed up. I'd transferred to an alternative school that offered dream studies instead of biology, so I was taking Defler's class for high-school credit, which meant that I was sitting in a college lecture hall at sixteen with words like mitosis and kinase inhibitors flying around. I was completely lost.

"Do we have to memorize everything on those diagrams?" one student yelled.

Yes, Defler said, we had to memorize the diagrams, and yes, they'd be on the test, but that didn't matter right then. What he wanted us to understand was that cells are amazing things: There are about one hundred trillion of them in our bodies, each so small that several thousand could fit on the period at the end of this sentence. They make up all our tissues - muscle, bone, blood - which in turn make up our organs.

Under the microscope, a cell looks a lot like a fried egg: It has a white (the cytoplasm) that's full of water and proteins to keep it fed, and a yolk (the nucleus) that holds all the genetic information that makes you you. The cytoplasm buzzes like a New York City street. It's crammed full of molecules and vessels endlessly shuttling enzymes and sugars from one part of the cell to another, pumping water, nutrients, and oxygen in and out of the cell. All the while, little cytoplasmic factories work 24/7, cranking out sugars, fats, proteins, and energy to keep the whole thing running and feed the nucleus. The nucleus is the brains of the operation; inside every nucleus within each cell in your body, there's an identical copy of your entire genome. That genome tells cells when to grow and divide and makes sure they do their jobs, whether that's controlling your heartbeat or helping your brain understand the words on this page.

Defler paced the front of the classroom telling us how mitosis - the process of cell division - makes it possible for embryos to grow into babies, and for our bodies to create new cells for healing wounds or replenishing blood we've lost. It was beautiful, he said, like a perfectly choreographed dance.

All it takes is one small mistake anywhere in the division process for cells to start growing out of control, he told us. Just one enzyme misfiring, just one wrong protein activation, and you could have cancer. Mitosis goes haywire, which is how it spreads.

"We learned that by studying cancer cells in culture," Defler said. He grinned and spun to face the board, where he wrote two words in enormous print: HENRIETTA LACKS.

Henrietta died in 1951 from a vicious case of cervical cancer, he told us. But before she died, a surgeon took samples of her tumor and put them in a petri dish. Scientists had been trying to keep human cells alive in culture for decades, but they all eventually died. Henrietta's were different: they reproduced an entire generation every twenty-four hours, and they never stopped. They became the first immortal human cells ever grown in a laboratory.

"Henrietta's cells have now been living outside her body far longer than they ever lived inside it," Defler said. If we went to almost any cell culture lab in the world and opened its freezers, he told us, we'd probably find millions - if not billions - of Henrietta's cells in small vials on ice.

Her cells were part of research into the genes that cause cancer and those that suppress it; they helped develop drugs for treating herpes, leukemia, influenza, hemophilia, and Parkinson's disease; and they've been used to study lactose digestion, sexually transmitted diseases, appendicitis, human longevity, mosquito mating, and the negative cellular effects of working in sewers. Their chromosomes and proteins have been studied with such detail and precision that scientists know their every quirk. Like guinea pigs and mice, Henrietta's cells have become the standard laboratory workhorse.

"HeLa cells were one of the most important things that happened to medicine in the last hundred years," Defler said.

Then, matter-of-factly, almost as an afterthought, he said, "She was a black woman." He erased her name in one fast swipe and blew the chalk from his hands. Class was over.

As the other students filed out of the room, I sat thinking, That's it? That's all we get? There has to be more to the story.

I followed Defler to his office.

"Where was she from?" I asked. "Did she know how important her cells were? Did she have any children?"

"I wish I could tell you," he said, "but no one knows anything about her."

After class, I ran home and threw myself onto my bed with my biology textbook. I looked up "cell culture" in the index, and there she was, a small parenthetical:

In culture, cancer cells can go on dividing indefinitely, if they have a continual supply of nutrients, and thus are said to be "immortal." A striking example is a cell line that has been reproducing in culture since 1951. (Cells of this line are called HeLa cells because their original source was a tumor removed from a woman named Henrietta Lacks.)

That was it. I looked up HeLa in my parents' encyclopedia, then my dictionary: No Henrietta.

As I graduated from high school and worked my way through college toward a biology degree, HeLa cells were omnipresent. I heard about them in histology, neurology, pathology; I used them in experiments on how neighboring cells communicate. But after Mr. Defler, no one mentioned Henrietta.

When I got my first computer in the mid-nineties and started using the Internet, I searched for information about her, but found only confused snippets: most sites said her name was Helen Lane; some said she died in the thirties; others said the forties, fifties, or even sixties. Some said ovarian cancer killed her, others said breast or cervical cancer.

Eventually I tracked down a few magazine articles about her from the seventies. Ebony quoted Henrietta's husband saying, "All I remember is that she had this disease, and right after she died they called me in the office wanting to get my permission to take a sample of some kind. I decided not to let them." Jet said the family was angry - angry that Henrietta's cells were being sold for twenty-five dollars a vial, and angry that articles had been published about the cells without their knowledge. It said, "Pounding in the back of their heads was a gnawing feeling that science and the press had taken advantage of them."

The articles all ran photos of Henrietta's family: her oldest son sitting at his dining room table in Baltimore, looking at a genetics textbook. Her middle son in military uniform, smiling and holding a baby. But one picture stood out more than any other: in it, Henrietta's daughter, Deborah Lacks, is surrounded by family, everyone smiling, arms around each other, eyes bright and excited. Except Deborah. She stands in the foreground looking alone, almost as if someone pasted her into the photo after the fact. She's twenty-six years old and beautiful, with short brown hair and catlike eyes. But those eyes glare at the camera, hard and serious. The caption said the family had found out just a few months earlier that Henrietta's cells were still alive, yet at that point she'd been dead for twenty-five years.

All of the stories mentioned that scientists had begun doing research on Henrietta's children, but the Lackses didn't seem to know what that research was for. They said they were being tested to see if they had the cancer that killed Henrietta, but according to the reporters, scientists were studying the Lacks family to learn more about Henrietta's cells. The stories quoted her son Lawrence, who wanted to know if the immortality of his mother's cells meant that he might live forever too. But one member of the family remained voiceless: Henrietta's daughter, Deborah.

As I worked my way through graduate school studying writing, I became fixated on the idea of someday telling Henrietta's story. At one point I even called directory assistance in Baltimore looking for Henrietta's husband, David Lacks, but he wasn't listed. I had the idea that I'd write a book that was a biography of both the cells and the woman they came from - someone's daughter, wife, and mother.

I couldn't have imagined it then, but that phone call would mark the beginning of a decadelong adventure through scientific laboratories, hospitals, and mental institutions, with a cast of characters that would include Nobel laureates, grocery store clerks, convicted felons, and a professional con artist. While trying to make sense of the history of cell culture and the complicated ethical debate surrounding the use of human tissues in research, I'd be accused of conspiracy and slammed into a wall both physically and metaphorically, and I'd eventually find myself on the receiving end of something that looked a lot like an exorcism. I did eventually meet Deborah, who would turn out to be one of the strongest and most resilient women I'd ever known. We'd form a deep personal bond, and slowly, without realizing it, I'd become a character in her story, and she in mine.

Deborah and I came from very different cultures: I grew up white and agnostic in the Pacific Northwest, my roots half New York Jew and half Midwestern Protestant; Deborah was a deeply religious black Christian from the South. I tended to leave the room when religion came up in conversation because it made me uncomfortable; Deborah's family tended toward preaching, faith healings, and sometimes voodoo. She grew up in a black neighborhood that was one of the poorest and most dangerous in the country; I grew up in a safe, quiet middle-class neighborhood in a predominantly white city and went to high school with a total of two black students. I was a science journalist who referred to all things supernatural as "woo-woo stuff"; Deborah believed Henrietta's spirit lived on in her cells, controlling the life of anyone who crossed its paths. Including me.

"How else do you explain why your science teacher knew her real name when everyone else called her Helen Lane?" Deborah would say. "She was trying to get your attention." This thinking would apply to everything in my life: when I married while writing this book, it was because Henrietta wanted someone to take care of me while I worked. When I divorced, it was because she'd decided he was getting in the way of the book. When an editor who insisted I take the Lacks family out of the book was injured in a mysterious accident, Deborah said that's what happens when you piss Henrietta off.

The Lackses challenged everything I thought I knew about faith, science, journalism, and race. Ultimately, this book is the result. It's not only the story of HeLa cells and Henrietta Lacks, but of Henrietta's family - particularly Deborah - and their lifelong struggle to make peace with the existence of those cells, and the science that made them possible.

Excerpted from The Immortal Life of Henrietta Lacks by Rebecca Skloot Copyright 2010 by Rebecca Skloot. Excerpted by permission of Crown, a division of Random House Inc. All rights reserved.

# data[].attributes.attachment_link.title
'Henrietta Lacks': A Donor's Immortal Legacy

# data[].attributes.attachment_link.description
In 1951, Henrietta Lacks died after a long battle with cervical cancer. Doctors cultured her cells without permission from her family. The story of those cells - known as HeLa cells, in Lacks' honor - and of the medical advances that came from them, is told in Rebecca Skloot's book, The Immortal Life of Henrietta Lacks.

# data[].attributes.attachment_link.readable_text
Journalist Rebecca Skloot's new book investigates how a poor black tobacco farmer had a groundbreaking impact on modern medicine

smithsonian.com

Medical researchers use laboratory-grown human cells to learn the intricacies of how cells work and test theories about the causes and treatment of diseases. The cell lines they need are "immortal"-they can grow indefinitely, be frozen for decades, divided into different batches and shared among scientists. In 1951, a scientist at Johns Hopkins Hospital in Baltimore, Maryland, created the first immortal human cell line with a tissue sample taken from a young black woman with cervical cancer. Those cells, called HeLa cells, quickly became invaluable to medical research-though their donor remained a mystery for decades. In her new book, The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells, Henrietta Lacks, and documents the cell line's impact on both modern medicine and the Lacks family.

Who was Henrietta Lacks?
She was a black tobacco farmer from southern Virginia who got cervical cancer when she was 30. A doctor at Johns Hopkins took a piece of her tumor without telling her and sent it down the hall to scientists there who had been trying to grow tissues in culture for decades without success. No one knows why, but her cells never died.

Why are her cells so important?
Henrietta's cells were the first immortal human cells ever grown in culture. They were essential to developing the polio vaccine. They went up in the first space missions to see what would happen to cells in zero gravity. Many scientific landmarks since then have used her cells, including cloning, gene mapping and in vitro fertilization.

There has been a lot of confusion over the years about the source of HeLa cells. Why?
When the cells were taken, they were given the code name HeLa, for the first two letters in Henrietta and Lacks. Today, anonymizing samples is a very important part of doing research on cells. But that wasn't something doctors worried about much in the 1950s, so they weren't terribly careful about her identity. When some members of the press got close to finding Henrietta's family, the researcher who'd grown the cells made up a pseudonym-Helen Lane-to throw the media off track. Other pseudonyms, like Helen Larsen, eventually showed up, too. Her real name didn't really leak out into the world until the 1970s.

How did you first get interested in this story?
I first learned about Henrietta in 1988. I was 16 and a student in a community college biology class. Everybody learns about these cells in basic biology, but what was unique about my situation was that my teacher actually knew Henrietta's real name and that she was black. But that's all he knew. The moment I heard about her, I became obsessed: Did she have any kids? What do they think about part of their mother being alive all these years after she died? Years later, when I started being interested in writing, one of the first stories I imagined myself writing was hers. But it wasn't until I went to grad school that I thought about trying to track down her family.

How did you win the trust of Henrietta's family?
Part of it was that I just wouldn't go away and was determined to tell the story. It took almost a year even to convince Henrietta's daughter, Deborah, to talk to me. I knew she was desperate to learn about her mother. So when I started doing my own research, I'd tell her everything I found. I went down to Clover, Virginia, where Henrietta was raised, and tracked down her cousins, then called Deborah and left these stories about Henrietta on her voice mail. Because part of what I was trying to convey to her was I wasn't hiding anything, that we could learn about her mother together. After a year, finally she said, fine, let's do this thing.

When did her family find out about Henrietta's cells?
Twenty-five years after Henrietta died, a scientist discovered that many cell cultures thought to be from other tissue types, including breast and prostate cells, were in fact HeLa cells. It turned out that HeLa cells could float on dust particles in the air and travel on unwashed hands and contaminate other cultures. It became an enormous controversy. In the midst of that, one group of scientists tracked down Henrietta's relatives to take some samples with hopes that they could use the family's DNA to make a map of Henrietta's genes so they could tell which cell cultures were HeLa and which weren't, to begin straightening out the contamination problem.

So a postdoc called Henrietta's husband one day. But he had a third-grade education and didn't even know what a cell was. The way he understood the phone call was: "We've got your wife. She's alive in a laboratory. We've been doing research on her for the last 25 years. And now we have to test your kids to see if they have cancer." Which wasn't what the researcher said at all. The scientists didn't know that the family didn't understand. From that point on, though, the family got sucked into this world of research they didn't understand, and the cells, in a sense, took over their lives.

How did they do that?
This was most true for Henrietta's daughter. Deborah never knew her mother; she was an infant when Henrietta died. She had always wanted to know who her mother was but no one ever talked about Henrietta. So when Deborah found out that this part of her mother was still alive she became desperate to understand what that meant: Did it hurt her mother when scientists injected her cells with viruses and toxins? Had scientists cloned her mother? And could those cells help scientists tell her about her mother, like what her favorite color was and if she liked to dance.

Deborah's brothers, though, didn't think much about the cells until they found out there was money involved. HeLa cells were the first human biological materials ever bought and sold, which helped launch a multi-billion-dollar industry. When Deborah's brothers found out that people were selling vials of their mother's cells, and that the family didn't get any of the resulting money, they got very angry. Henrietta's family has lived in poverty most of their lives, and many of them can't afford health insurance. One of her sons was homeless and living on the streets of Baltimore. So the family launched a campaign to get some of what they felt they were owed financially. It consumed their lives in that way.

What are the lessons from this book?
For scientists, one of the lessons is that there are human beings behind every biological sample used in the laboratory. So much of science today revolves around using human biological tissue of some kind. For scientists, cells are often just like tubes or fruit flies-they're just inanimate tools that are always there in the lab. The people behind those samples often have their own thoughts and feelings about what should happen to their tissues, but they're usually left out of the equation.

And for the rest of us?
The story of HeLa cells and what happened with Henrietta has often been held up as an example of a racist white scientist doing something malicious to a black woman. But that's not accurate. The real story is much more subtle and complicated. What is very true about science is that there are human beings behind it and sometimes even with the best of intentions things go wrong.

One of the things I don't want people to take from the story is the idea that tissue culture is bad. So much of medicine today depends on tissue culture. HIV tests, many basic drugs, all of our vaccines-we would have none of that if it wasn't for scientists collecting cells from people and growing them. And the need for these cells is going to get greater, not less. Instead of saying we don't want that to happen, we just need to look at how it can happen in a way that everyone is OK with.

About Sarah Zielinski

# data[].attributes.attachment_link.description
smithsonian.com Medical researchers use laboratory-grown human cells to learn the intricacies of how cells work and test theories about the causes and treatment of diseases. The cell lines they need are "immortal"-they can grow indefinitely, be frozen for decades, divided into different batches and shared among scientists.

# data[].attributes.attachment_link.readable_text
On its own, the HeLa genome doesn't say anything specific about Lacks: it's a string of billions of letters that detail the genetic information that makes up a HeLa cell, which is useful for science. A news release from the European Molecular Biology Laboratory, where the HeLa genome was sequenced, said, "We cannot infer anything about Henrietta Lacks's genome, or of her descendants, from the data generated in this study."

But that's not true. And a few scientists decided to prove it. One uploaded HeLa's genome to a public Web site called SNPedia, a Wikipedia-like site for translating genetic information. Minutes later, it produced a report full of personal information about Henrietta Lacks, and her family. (The scientist kept that report confidential, sharing it only with me.) Until recently, few people had the ability to process raw genome data like this. Now anyone who can send an e-mail can do it. No one knows what we may someday learn about Lacks's great-grandchildren from her genome, but we know this: the view we have today of genomes is like a world map, but Google Street View is coming very soon.

Scientifically speaking, that's good news. There's a lot of hope for using technology like this for affordable "personalized medicine." But legally and ethically speaking, we're not ready for it.

As Francis S. Collins, director of the National Institutes of Health, says: "This latest HeLa situation really shows us that our policy is lagging years and maybe decades behind the science. It's time to catch up." The regulations governing this sort of research were written in the 1970s, long before anyone imagined what you could learn from a bit of DNA. They are largely based on the now outdated belief that if samples are "anonymized" (i.e., your name is removed), there's no need to get consent before using them in research.

The problem, says Yaniv Erlich, a fellow at the Whitehead Institute for Biomedical Research, is that anonymity vanishes when it comes to DNA: "People don't realize it's impossible to hide genetic information once it's out there." He and his colleagues recently proved that it's possible to use online public databases to find the identities of people whose anonymous DNA samples had been sequenced and published online. Yet researchers aren't required to tell you that there is no guarantee that a genome, once sequenced, will stay private or anonymous.

More than a year and a half ago, the N.I.H. and several government organizations proposed changing current regulations to require consent for tissue research, genome sequencing and sharing private data. The proposal generated public comment but nothing changed, and science continues to move forward with speed, potential and outdated regulation.

The Lackses' experiences over the last 60 years foretold nearly every major ethical issue raised by research on human tissues and genetic material. Now they're raising a new round of ethical questions for science: though their consent is not (yet) required for publishing private genetic information from HeLa, should it be? Should we require consent before anyone's genome is sequenced and published? And what control should gene-sharing family members have?

The Lacks family is proud of HeLa's contributions to society, and they don't want to stop HeLa research. But they do want to learn about the HeLa genome - how it can be used for the good of science while still protecting the family's privacy - so they can decide whether to consent to its publication. And they want researchers to acknowledge that HeLa cells are not anonymous and should be treated accordingly.

After hearing from the Lacks family, the European team apologized, revised the news release and quietly took the data off-line. (At least 15 people had already downloaded it.) They also pointed to other databases that had published portions of Henrietta Lacks's genetic data (also without consent). They hope to talk with the Lacks family to determine how to handle the HeLa genome while working toward creating international standards for handling these issues.

The publication of the HeLa genome without consent isn't an example of a few researchers making a mistake. The whole system allowed it. Everyone involved followed standard practices. They presented their research at conferences and in a peer-reviewed journal. No one raised questions about consent.

In the three years since my book about HeLa was published, the Lacks family and I have spoken to audiences by the thousands about these issues. Public response is overwhelmingly consistent and in line with several studies: the public supports the science and wants to help it move forward. But that support is dependent on consent and trust.

# data[].attributes.attachment_link.title
Opinion | The Immortal Life of Henrietta Lacks, the Sequel

# data[].attributes.attachment_link.description
On its own, the HeLa genome doesn't say anything specific about Lacks: it's a string of billions of letters that detail the genetic information that makes up a HeLa cell, which is useful for science.

# data[].attributes.attachment_link.description
This character was seen as "simple" but she probably suffered from epilepsy or mental retardation. , Mary was the assistant to this doctor and cell research specialist. , This doctor tested the effects of cancerous HeLa cells on his uninformed patients and test subjects by injecting them with her cells.