The Big Similarities & Quirky Differences Between Our Left and Right Brains

A broken symmetry from our evolutionary heritage is part of what makes us human.

by Carl Zimmer

From the May 2009 issue, published online April 15, 2009

 

There is nothing more humbling or more perception-changing than holding a human brain in your hands. I discovered this recently at a brain-cutting lesson given byJean-Paul Vonsattel, a neuropathologist at Columbia University. These lessons take place every month in a cold, windowless room deep within the university’s College of Physicians and Surgeons. On the day I visited, there were half a dozen brains sitting on a table. Vonsattel began by passing them around so the medical students could take a closer look. When a brain came my way, I cradled it and found myself puzzling over its mirror symmetry. It was as if someone had glued two smaller brains together to make a bigger one.

Vonsattel then showed us just how weak that glue is. He took back one of the brains and used a knife to divide the hemispheres. He sliced quickly through the corpus callosum, the flat bundle of nerve fibers that connects the halves. The hemispheres flopped away from each other, two identical slabs of fleshy neurons.

Sometimes surgeons must make an even more extreme kind of slice in the brain of a patient. A child may suffer from epilepsy so severe that the only relief doctors can offer is to open up the skull and cut out the entire hemisphere in which the seizures start. After the surgery, the space soon fills with cerebrospinal fluid. It may take a child a year of physical therapy to recover from losing a hemisphere—but the fact that patients recover at all is stunning when you consider that they have only half a brain. It makes you wonder what good two hemispheres are in the first place.

In fact, scientists have spent a lot of time pondering this very question. Their best answer has a lot to do with the form and evolutionary history of our bodies. From early in our development as embryos, humans take on a left-right symmetry that eventually gives rise to our two eyes, our two big toes, and every paired structure in between. All vertebrates are symmetrical in the same way, as are butterflies, scorpions, and a vast number of other invertebrates. This left-right structure is probably inherited from the common ancestor of all bilaterally symmetric animals*, a creature that apparently emerged over 570 million years ago.

There were some obvious survival benefits from left-right symmetry. With muscles and limbs on both sides of their bodies, animals could move forward quickly and efficiently. Once established, symmetry had a powerful effect on how new organs evolved. Eyes and antennae tended to develop in left-right pairs, for example. When early fish began to evolve complex brains, those too developed according to left-right rules. The human brain is very different from the brain of a lamprey, but in both species the neocortex—the outer layers of the brain—is divided into two mirror-image hemispheres.

Of course, our bodies are not perfectly symmetrical (heart on the left, appendix on the right), and neither are our brains. Some regions are slightly bigger on one side than on the other, and these differences translate into imbalances in how the human brain works. Most people, for example, tend to favor their right hand over their left. In the mid-1800s, the French physician Paul Broca discovered a region on the left side of the brain that is essential for language; damage to Broca’s area, as it is called, leaves people unable to talk. The same region on the right side is not so vital. Another area, on the underside of the brain, is important for recognizing people’s faces. The right half of this region, known as the facial fusiform area, does most of the work of recognizing. In fact, if people view a face only through their left eye (which is linked to the brain’s right hemisphere), they will do a better job of recognizing it than if they use only their right eye.

These sorts of findings helped to turn the hemispheres into pop phenoms. People were tagged as “right brains” if they could draw and “left brains” if they were analytical. Academics made some big claims about the hemispheres as well. In the 1990s psychologist Michael Corballis of the University of Auckland in New Zealand argued that the asymmetry of the brain—known as lateralization—was a key step in the evolution of our species, giving us language and additional mental powers that other animals lack.

Today Corballis readily admits he was wrong. Lateralized brains are not unique to humans. Parrots prefer picking up things with their left foot. Toads tend to attack other toads from the right but go after prey from the left. Zebra fish are likely to look at new things with their right eye and familiar things with their left. Even invertebrates are biased. Pinar Letzkus, a vision researcher at Australian National University, rewarded bees with sugar whenever they extended their tongue at the sight of a yellow rectangle on a computer screen. He then fashioned tiny eye patches and put them on a new set of subjects. Bees with their left eye covered learned almost as quickly as did bees without a patch. But bees with their right eye covered did far worse.

The broken symmetry of the nervous system may thus be as old as the symmetry itself. If so, it is an ancient puzzle. Being biased to one side would seem like a serious handicap: A toad that hopped to the left whenever it was startled by a predator, for instance, would be easy prey for an attacker that could anticipate which way it would go; the same holds for any other kind of ingrained behavioral imbalance. A number of scientists have run experiments to find the benefits that might offset such costs.

One hypothesis is that a lateralized brain is more powerful than one that works like a mirror image. Instead of two matching parts of the brain performing an identical task, one can take charge, leaving the other free to do something else. Lesley Rogers, a biologist at the University of New England in Australia, tested this hypothesis on chickens. The birds use their left hemisphere to peck for seeds and their right hemisphere to detect predators. Some chickens have more lateralized brains than others, and there is a simple way to make any chicken more lateralized: Just shine a light on it while it is still in the egg. Chick embryos usually develop with the left eye tucked inward and the right eye facing out. The stimulation of light on the right eye alters the developing left-brain hemisphere but not the right.

Rogers and her colleagues reared 27 chicks that had been exposed to light and 24 that had not. Each day the researchers put the chicks in a special box with grain and pebbles scattered on the floor; at the same time, they distracted the birds by moving a hawk-shaped cutout overhead. They then observed how well the chicks were able to distinguish between pebbles and grain. Light-exposed chicks learned to do a much better job. Rogers concludes that lateralized brains allowed the chicks to multitask more effectively, with each eye handling a separate job.

The pop psychology notion of a left brain and a right brain doesn’t capture their intimate relationship. The left specializes in the sounds that form words; the right is more sensitive to the emotions of language.

David Stark of Harvard Medical School recently found additional clues about lateralization in his studies of 112 different regions in the brains of volunteers. He and his collaborators discovered that the front portions of the brain are generally less tightly synchronized across the hemispheres than are the ones in the back. It may be no coincidence that the highly synchronized back regions handle basic functions like seeing. To observe the world, it helps to have unified vision. At the front of the hemispheres, in contrast, we weave together streams of thought to produce complex, long-term plans for the future. It makes sense that these areas of the brain would be more free to drift apart from their mirror-image partners.

No matter how lateralized the brain can get, though, the two sides still work together. The pop psychology notion of a left brain and a right brain doesn’t capture their intimate working relationship. The left hemisphere specializes in picking out the sounds that form words and working out the syntax of the words, for example, but it does not have a monopoly on language processing. The right hemisphere is actually more sensitive to the emotional features of language, tuning in to the slow rhythms of speech that carry intonation and stress.

Neuroscientists know that the hemispheres work together and that they do so by communicating through the corpus callosum. But exactly how the hemispheres cooperate is not so clear. Perhaps paired regions take turns being dominant. That is known to happen in some animals. For instance, dolphins use this strategy to sleep and swim at the same time: One hemisphere remains active for hours, then fades while the other takes over. Bird brains switch as well. In order to sing, a songbird makes the two sides of its lungs open and close. The two hemispheres of the bird’s brain take turns controlling the song, each dominating for a hundredth of a second.

The intimate cooperation between the two hemispheres makes it all the more remarkable that a person can survive with just one—a sign that the brain is far more malleable than we once thought. After a hemisphere is forced to manage on its own, it can rewire itself to handle all the tasks of a full brain. In fact, two hemispheres can cause more trouble than one if they cannot talk clearly to each other. Neuro scientists have linked some mental disorders, including dyslexia and Alzheimer’s, with a breakdown in left-right communication.

The two sides of the brain may be a legacy that we inherited from our wormlike ancestors. But their delicate balance of symmetry and specialization is now woven into the very essence of human nature.

Priority Setting in Biomedical Research

Rebecca Dresser, JD

The 21st century is replete with exciting discoveries in biomedical science. Even a superficial review of research conducted at or funded by the U.S. National Institutes of Health (NIH) supplies irrefutable evidence of the enormous range of opportunities that exists today. A survey of studies occurring in the private sector only adds to this evidence. And researchers in every field are enthusiastic about the knowledge and clinical benefits that their work could deliver.

LEARNING OBJECTIVEIdentify the social-justice issues raised by public and private-sector choices about allocation of funding to research and public health.

The array of promising research areas presents itself in a context of limited resources, however. The NIH and private-sector funding sources must make difficult decisions about the fields and specific studies to support and must do so in a nation and world full of people vulnerable to an immense number of health problems.

Research-funding entities use broad criteria to allocate their limited resources. Under pressure to articulate the government’s decision-making process, NIH officials issued a document explaining their allocation criteria in 1997. Five considerations play a role in the agency’s spending choices: (1) public health needs; (2) scientific merit of specific study proposals; (3) potential for advances in a particular area; (4) distribution across diverse research areas (because it is impossible to predict exactly where advances will occur); and (5) national training and infrastructure needs.

The first NIH criterion, public health needs, is determined by the:

• Number of people with a specific disease.
• Number of deaths a specific disease causes.
• Degree of disability a specific disease produces.
• How much a specific disease shortens the average human lifespan.
• A specific disease’s financial and social costs.
• Threats posed to others by contagious disease.

According to the NIH, these considerations are of equal importance in allocating research resources [1].

Resource allocation in the private sector may incorporate some of the same considerations as the NIH applies, but other factors play a role too. Pharmaceutical, biotechnology, and other companies are profit-making entities that consider the size of anticipated financial return as an essential guide to research investments. And nonprofit organizations often limit their support to research that could assist their specific disease constituencies.

Public and private choices about allocation of resources for research and public health needs raise social-justice issues. The ethical question is whether these funding sources make fair decisions about where to invest their resources. The NIH has the clearest obligation to distribute its resources fairly because it is taxpayer-supported. There is disagreement over whether private organizations have this obligation too; some believe that even businesses have a responsibility to consider the public good in their research investments [2].

The problem lies in deciding what qualifies as a fair allocation decision. The NIH lists factors that many people would use to determine fairness, but fails to rank them according to their importance. Moreover, its priority-setting criteria omit other ethical considerations that could bear on fairness, such as the relative significance of research needs of people in the United States compared to those in poor nations.

Not much attention is paid to fairness in research priority setting, but some writers have explored the topic and questioned the fairness of the NIH’s current approach to resource allocation. For example, some criticize it for allowing current politics and political correctness to shape its allocation decisions [3]. A related charge is that interest-group lobbying plays too heavy a role. Others contend that the NIH should do more to show that its choices are aimed at conditions that impose the heaviest personal and social burdens. And at least one critic argues that the current criteria place too heavy an emphasis on extending the average lifespan and not enough on public health, disease prevention, and disability reduction [4].

It is not surprising that clear consensus is lacking on defensible research priorities. As the NIH criteria illustrate, there are many variables, and people differ in the value they assign to each. Is it more important to study childhood diseases than diseases affecting older individuals? Is extending life more important than ameliorating the burdensome symptoms of illness? Should life-threatening diseases that affect a small number of people take priority in the research agenda over less-serious diseases that affect many more individuals? Is it better to invest money in areas where breakthroughs appear imminent or in less-promising areas, where investments might jump-start research progress? People answer these questions differently based on their values and personal experiences with disease [5, 6].

Social justice becomes even more critical in the international context. Discussions of international research priorities often refer to the 10/90 split. Estimates are that just 10 percent of research focuses on the diseases that are responsible for 90 percent of the world’s health problems. Most research occurs in wealthy countries and tends to study the diseases that affect people living in those countries [7]. Is it defensible for wealthy countries to devote so little to research on conditions like malaria, tuberculosis, diarrhea, and malnutrition, and so much to conditions that affect primarily people fortunate enough to live into their later decades [8]?

It may seem shocking to raise questions about the fairness of the current approach to biomedical research funding. But Daniel Callahan, a noted writer on bioethics and health policy, presents the following thought experiment:

Consider—as an imaginative exercise—what we would get if there was no progress at all from this point forward, and medicine remained restricted to what is now available. The rich countries would remain rich. Most of their citizens would make it to old age in reasonably good health. There would continue to be incremental gains in mortality and morbidity, the fruits of improved social, economic, and educational conditions, and improvements in the evaluation and use of present therapies. No prosperous country would sink from the lack of medical advances [4].

Callahan’s points relate to a second matter of social justice, which concerns the trade-offs between funding research and established health care. The United States has a poor record of providing basic health care to its people. Estimates are that more than 40 million individuals lack health insurance coverage and even more have inadequate coverage [9]. As a result, a large part of the community has trouble obtaining established therapies that could extend and improve their lives. This situation raises questions about the justification for investing large amounts of money in research aimed at developing health care innovations, especially those that are likely to be expensive. As health plans expand to cover the fruits of emerging biomedical research, the added costs can lead to even more disparities in health care access.

Advocates contend that research is needed to assist people with illnesses or injuries that cannot now be adequately treated. For them, social justice supports research that assists this disadvantaged group. They see a “research imperative” to conduct studies that could save lives and avoid suffering by those who cannot be helped by established medicine [10].

The case for a moral duty to undertake research must consider a second position, however. Investing resources to expand access to standard health interventions would also save lives and avoid suffering among people now deprived of this help. Most established therapies have already been evaluated in research, their benefits are well known, and they are relatively inexpensive. In poor nations, many children and adults die from easily prevented or treatable diseases because their countries cannot afford to provide them with effective medicines [11]. For example, the HIV epidemic has imposed untold suffering and devastating social burdens on people unable to obtain treatment [12].

Should limited resources be invested in research to develop health care innovations or to allow more people to benefit from already existing therapies? This question is rarely addressed in debates about U.S. biomedical priorities [13]. The social-justice inquiry raises questions about which areas of biomedical research merit the highest priority and the relative priority of biomedical research when compared to health care delivery. Delivering meaningful help to people in need requires difficult choices about where to place our nation’s limited resources.

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References

1. National Institutes of Health. Setting Research Priorities at the National Institutes of Health. Bethesda, MD: National Institutes of Health. 1997.
2. Dresser R. Private-sector research ethics: marketing or good conflicts management? The 2005 John J. Conley Lecture on Medical Ethics. Theor Med Bioeth. 2006;27(2):115-139.
3. Johnson JA. Disease Funding and NIH Priority Setting. CRS Report for Congress. Report 97-917 STM. Washington, DC: Congressional Research Service; 1998.
4. Callahan D. What Price Better Health? Hazards of the Research Imperative. Berkeley, CA: University of California Press; 2003.
5. Daniels N, Sabin J. Limits to health care: fair procedures, democratic deliberation, and the legitimacy problem for insurers. Philos Public Aff.1997;26(4):303-350.
6. Dresser R. When Science Offers Salvation: Patient Advocacy and Research Ethics. New York, NY: Oxford University Press; 2001.
7. Huang F, Stremlau M. Disease researchers neglecting world poor. Los Angeles Times. April 30, 2002.
8. Utzinger J, de Savigny D. Control of neglected tropical diseases: integrated chemotherapy and beyond. PLoS Med. 2006;3(5):e112. http://medicine.plosjournals.org/perlserv/?request=get-document& doi=10.1371/journal.pmed.0030112.
9. DeNavas-Walt C, Proctor B, Lee C. Income, Poverty and Health Insurance Coverage in the United States: 2005. The Census Bureau Report.Washington, DC: Government Printing Office; 2006.
10. Callahan D. Death and the research imperative. N Engl J Med. 2000;342(9):654-656.
11. Cohen J. Global health. The new world of global health. Science.2006;311(5758):162-167.
12. Lange JM, Thaineua V. Access for all? Science. 2004;304(5679):1875.
13. Morgan JJ, Lee TH. Do we really want broad access to health care? N Engl J Med. 2005;352(12):1260-1263.

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Rebecca Dresser, JD, is the Daniel Noyes Kirby Professor of Law and professor of ethics in medicine at Washington University in St. Louis. Since 1983, she has taught medical and law students about legal and ethical issues in end-of-life care, biomedical research, genetics, assisted reproduction, and related topics. She has been a member of the President’s Council on Bioethics since 2002.

Related in VM

The History and Role of Institutional Review Boards, April 2009

How to handle patients who are always late

Practice Management. By Karen Caffarini, AMNews staff. Posted April 13, 2009.

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Just about every medical practice has chronically tardy patients, the ones who arrive half an hour to an hour after the scheduled appointment time and demand to be squeezed in.

Experts say these patients do more than just try the receptionist's patience. They could cause lost revenue, make on-time patients wait and sometimes force staff to rack up overtime.

They say practices can avoid this problem by changing the behavior of the tardy patient, that of the staff toward that patient and that of the practice itself, if necessary. That means instituting disincentives for the tardy patient that stay in place until their on-time record improves, experts say. Staff should create a system of reminders and scheduling changes to accommodate these patients. But first, the practice needs to establish a tardiness policy, experts say.

"The goal is to change the patient's behavior so they show up for their appointment at the right time," said Jack Valancy, a practice management consultant in Cleveland Heights, Ohio.

Experts say making late patients wait can be effective in changing their cavalier attitudes toward time. Latecomers should be told that because they are late they need to wait until all the on-time patients have been seen. For some practices, this could mean the latecomer is the last person seen that day.

"Everybody who showed up on time should not be punished because of someone else," said Reed Tinsley, a health care consultant from Houston.

Tinsley said if the patient protests, he or she can be allowed to reschedule for another day. But late patients must be told that if they are late again, they will wait again, Tinsley said.

Tinsley said a practice needs to draw the line about how late a patient can be and still be seen that day. He said one hour is a good limit.

Valancy recommends putting chronic latecomers on a virtual doctor list. These patients need to wait until the first doctor in the practice (not necessarily their own doctor) is available, after all the on-time patients have been seen. Do this every time these patients come in, whether they are late or not. Once they establish a routine of coming in on time, they can gradually return to their regular schedule with their regular doctor, Valancy said.

Patients who are chronically tardy can be charged a late fee, provided your insurers don't specifically disallow these fees, said Alice Berkowitz, PhD, executive director of Practice Management Consultant Co. LLC in New York. As a last resort, the patient can be discharged from the practice.

Experts say if staff members notice a patient is continuously running late, they need to take the initiative to preempt any potential scheduling problems.

Call the patient a day or two before the appointment with a reminder of the day and time, emphasizing the time, Berkowitz said. Valancy said studies show reminders reduce the number of no-shows by 20% to 25%, and could work for late-shows, as well.

Call again on the day of the appointment to make sure the patient is running on time. Also, the doctor can give the patient a gentle reminder on why being on time is important for all the patients.

Most practice management software has pop-ups that alert staff to a patient who is usually late and needs to be reminded, experts say. This also allows staff to do some creative scheduling. One medical practice gives the patient an appointment card with a time 30 minutes to an hour earlier than is scheduled in the appointment book, Tinsley said.

Experts say practices can stagger schedules, such as having so many people arrive every 15 minutes, or straddle longer appointments with shorter ones so a tardy person could be squeezed in if there is a gap.

They don't recommend overbooking, as it could backfire by prompting on-time patients to become late patients to avoid the long wait times double-booking often causes.

And, before getting tough on patients, experts suggest the practice look at its own late record. "You need to run your practice smoothly and fairly on time if you expect patients to be on time," Valancy said.

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Caffarini covered practice management issues during 2008-09. If you have any questions or comments, please contact Business Editor Bob Cook at 312-464-4434 or by e-mail (bob.cook@ama-assn.org).

Suspected Ethical Misconduct in Research: Virtual Mentor

Commentary by Timothy M. Pawlik, MD, MPH

Michael, an MD/PhD student, was working for Dr. Adams, an ambitious, tenure-track associate professor who specialized in several rare genetic diseases. Michael was working on a project of his own, but he heard updates about all of the projects in the research group during a weekly lab meeting.

LEARNING OBJECTIVEIdentify the information gathering and other steps that should be taken when one suspects a colleague of ethical misconduct in research.

Michael was rather surprised when, at one of the lab meetings, Dr. Adams announced that the results of a recently concluded clinical trial were positive and had been submitted to a prestigious journal for possible publication. No one else acted surprised or asked Dr. Adams any questions about this report.

After the lab meeting, Michael and his postdoctoral fellow, Lisa, grabbed a cup of coffee before starting their work. Michael said, “It’s kind of surprising that Dr. Adams’ study results were positive. For the last year, everyone has been grumbling about how badly the study was going.”

Lisa, who was also uninvolved in the study, said “Well, that’s why we have peer review. If there are any inconsistencies, they’ll get picked up. So, any big plans this weekend?”

Despite Michael’s marginal involvement with the study, inexperience in the conduct of clinical trials, and lack of training in statistical methodologies, he could not shake the feeling that something was amiss.

In a moment of privacy with Teddy, one of the more junior members of the lab and a listed co-author on the paper, Michael casually mentioned, “Congrats on finishing the paper. That’s pretty exciting. I thought you guys were having trouble recruiting people that fit the inclusion criteria, but it seems like everything has come together.”

Teddy responded, “Thanks, but I can’t take too much credit. In the last few months, Dr. Adams really became more hands-on with this trial. He pretty much took over every aspect of it, which was nice because I have been able to wrap up some loose ends with a few other projects. To tell you the truth, I was pretty surprised when he said it was over and ready to submit for publication.”

Commentary

When conducting scientific research, residents and students need to be mindful of unethical activity in which they may be directly or indirectly involved. Although it is not the job of residents and students to act as investigators and monitor the ethical behavior of every fellow researcher, they do need to be aware of possible scientific misconduct in the research setting. In fact, a scrutinizing eye toward one’s colleague’s conduct is both scientifically and ethically desirable. Not only is this part of one’s moral duty, but remaining vigilant in the research environment also helps to maintain high standards of scientific integrity. As in this case, however, residents and students will often not directly witness scientific misconduct or fraud, such as a researcher changing data points or manipulating experimental conditions and study eligibility criteria to suit his or her needs. Rather, scientific misconduct is more frequently suspected based on circumstantial evidence. For example, in the current case, Michael did not directly witness Dr. Adams violating the inclusion criteria of the study to facilitate increased trial accrual. Rather, he had a feeling that something was amiss based on Dr. Adams’ positive study results. Although Michael has no direct evidence to prove that Dr. Adams has acted wrongly, he has a strong suspicion, and therefore an ethical duty to act. But what should Michael do?

Gathering Information

Accusing a researcher of ethical misconduct is a serious matter. The shadow of an accusation can hang over someone’s career even if later investigations exonerate the individual. A number of criteria need to be satisfied before “blowing the whistle.” First, Michael has a responsibility to ensure his information is accurate and based on a thorough understanding of Dr. Adams’ work. For example, suppose Dr. Adams—realizing that study-inclusion criteria were too strict and severely limited accrual—had applied for and received institutional review board (IRB) approval for revised study-inclusion criteria. Perhaps this is how Dr. Adams had become more hands-on with this trial, and these new IRB-approved inclusion criteria were the reason for the newfound success of the trial. Since Michael is inexperienced in the conduct of clinical trials and lacks training in statistical methodologies, he may not be able to assess accurately whether Dr. Adams is engaging in unethical behavior.

Did Dr. Adams purposely miscalculate the sample size in the study to meet anticipated low accrual or accept a lower statistical power for the study because he anticipated low accrual? Sometimes only an individual with specialized knowledge is in the position to identify behavior as unethical. On the other hand, Dr. Adams may indeed have accrued patients outside the inclusion criteria or manipulated data. Since Michael has his own project and only hears about other projects in the research group during weekly lab meetings, he may not be fully up-to-date on the trial. Michael may be able to get more information by talking with other colleagues in the lab. Discussions with colleagues should be undertaken in a nonaccusatory manner and reflect a genuine desire to understand how the study was completed successfully. If the matter cannot be clarified by this means, Michael should consider talking directly to Dr. Adams.

Facing the Problem One-on-One

In general, a prospective accuser should first attempt to confront the researcher he thinks is performing the ethically questionable activity. If Michael chooses to do this, however, the conversation must be handled with care and in a nonconfrontational manner. Ideally, after identifying an ethically questionable situation, the concerned resident or student should approach the researcher in question to allow him or her the opportunity to clarify, or even rectify, what may be an honest, unintended misunderstanding or error. Michael might say, for example, “Dr. Adams, I was happy to hear that your research project had a positive outcome after the early setbacks last year. What was the main reason for the turnaround?” Unfortunately, even this can be an unrealistic expectation. Fear of retaliation or being blackballed by the entire research team or community often makes an open conversation about these issues unworkable, especially in situations where there is a power disequilibrium involving residents or students. If a researcher feels threatened by a resident or student who is questioning his or her work, that faculty member may be inclined to retaliate, affecting the individual’s career path adversely. On the other hand, if the resident or student proceeds directly to an institutional review process without first approaching the researcher in question, the opportunity to remedy the situation before it becomes public is lost. This course of events would be especially damaging to the resident or student if the complaint were found to be erroneous and based on a misunderstanding of the situation.

When a resident or student suspects ethical misconduct, he or she should initially report the suspected ethical misconduct to an appropriate, trusted individual—ideally not another resident or student, but someone of an academic stature who could effectively investigate the matter as an advocate without fear of repercussions. After gathering more information and confirming that there is an ethical concern, Michael can execute his moral duty by “kicking it up the ladder.” With the assistance of a mentor, Michael can help assure that his concerns are communicated to the appropriate authorities for further investigation and adjudication.

Managing the Situation

Michael has a responsibility to report suspected—and substantiated—ethical misconduct to the appropriate authorities. He should not, however, gossip about suspected ethical misconduct with friends, colleagues, or unsanctioned individuals outside the department or hospital. As noted, discussions of suspected ethical misconduct are best initiated with one’s departmental mentor who can then assist in further investigating the situation before reporting the incident. By reporting to appropriate authorities such as departmental mentors or division chiefs, Michael will be respecting the due process that Dr. Adams deserves.

If indeed the suspicion of ethical-research misconduct rises to the level of a formal complaint to the departmental authoritative body, a full formal investigation usually ensues. Depending on the situation, this may range from review of data files and trial folders, interviews with research nurses and participants, or even the involvement of legal authorities. Most institutions have a system to deal with suspected scientific misconduct that includes assessing the validity of the accusation, properly investigating the grievance, and establishing punishment or rectifying the situation.

Conclusion

Michael’s moral duty lies not in acting as investigator, judge, or jury of suspected ethical-research misconduct. Rather, his moral duty is to be aware of possible scientific misconduct. When misconduct is suspected, Michael has an ethical duty to ensure that he has his facts straight. He should not engage in unconstructive gossip about any of his suspicions, but should talk with Dr. Adams about the research project and its surprise outcome. More realistically, Michael should enlist the support of a trusted mentor who can help explore his sense that something is amiss. If, in conversations and exploration of the facts with this mentor, the concerns remain, the mentor can assist Michael in formally reporting the suspected ethical misconduct to the appropriate departmental or institutional authorities.

Timothy M. Pawlik, MD, MPH, is an associate professor of surgery and oncology at Johns Hopkins University School of Medicine in Baltimore. In addition to completing his residency at the University of Michigan and a surgical oncology fellowship at the University of Texas M. D. Anderson Cancer Center, Dr. Pawlik attended Harvard Divinity School, where he obtained a master’s degree in theological studies. Dr. Pawlik is the hepatobiliary surgery program director, and his research interests include clinical trials and outcomes for HPB malignancies.

CHIP reauthorization increasing extent of kids' coverage

About a dozen states are implementing or considering CHIP eligibility expansions.

By Doug Trapp, AMNews staff. Posted April 13, 2009.

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Washington -- States began expanding health coverage for children even before the recently enacted Children's Health Insurance Program reauthorization took effect on April 1.

The CHIP reauthorization, signed into law in February by President Obama, funds the federal/state program through September 2013 and is expected to expand coverage by 4 million to reach 11 million children by that year. The act pays for the $33 billion of additional funding almost entirely by increasing the federal tobacco tax.

The CHIP act will help fill three big gaps in the U.S. health system: Primary, dental and mental health care, said Ted Epperly, MD, president of the American Academy of Family Physicians. The act requires states to add dental services to CHIP plans and to offer mental health and substance abuse coverage equal to the state's medical and surgical benefits. The reauthorization also allows some states to offer separate dental coverage to CHIP-eligible kids.

"They're really going after the big three, where there's just a tremendous need. I can't applaud the administration enough," Dr. Epperly said. The reauthorization also provides stability to patient care, he said, following many months of uncertainty about the program's future.

CHIP has allowed about a dozen states to expand eligibility or consider doing so, said Jennifer Tolbert, principal policy analyst with the Kaiser Commission on Medicaid and the Uninsured. "Given the current economic situation, it's a pretty significant number," she said. The act lets states receive enhanced federal matching funds to cover children in families earning up to 300% of the federal poverty level. The federal government pays for at least 65% of CHIP spending.

CHIP no longer covers childless adults.

Several states had adopted CHIP expansions while President Bush was in office. But they were handcuffed by a Centers for Medicare & Medicaid Services directive effective Aug. 17, 2008, that limited enhanced federal CHIP funding for children in families earning 250% of poverty or more. CMS never officially enforced that directive, and Obama rescinded it in February.

The Oklahoma Legislature, for example, in 2007 expanded the state's CHIP eligibility from 185% of poverty to 300% of poverty, said Jo Kilgore, spokeswoman for the Oklahoma Health Care Authority, the state's Medicaid agency. But the state never implemented the law because of the CMS directive.

The state recently sent a request to CMS to verify that it would receive the federal matching funding necessary to carry out the CHIP expansion, which is expected to cover 40,000 more children, Kilgore said. Other states whose expansions were hampered by the directive -- such as Ohio, Louisiana and Washington -- are considering or have made similar moves recently, Tolbert said.

Fewer adults allowed

The CHIP reauthorization also changes the program by ending coverage for childless adults by the end of this year. In recent years, the program had covered 600,000 such adults.

But the act allows a state to use CHIP to cover pregnant women if the state's Medicaid program covers lower-income women and if it meets other criteria. Dr. Epperly said pregnant women who are abusing drugs sometimes show up as patients in his Boise, Idaho, practice. He said this provision should help get these women care that will prevent health problems for them and their children.

CHIP also allows states to help low-income parents buy employer-sponsored health insurance, which should remove some of the financial pressures CHIP might place on states, said American Medical Association President Nancy H. Nielsen, MD, PhD. Dr. Epperly said his practice is looking into this assistance option for some of its 145 employees. "I'd as soon keep them in our [health] plan than have them get off our plan and go to CHIP," he said.

CHIP enrollment also will be helped by other provisions, including $100 million in federal funding for states to conduct outreach to children who are eligible for CHIP but not yet signed up. And instead of states running deficits when they exceed enrollment goals, the reauthorization provides $3.2 billion for bonus payments to states that beat their goals if the state also adopts at least five measures to facilitate enrollment. These include ending in-person enrollment interviews, providing help with buying private insurance, and reducing asset tests or documentation requirements.

Stimulus a key

The $87 billion Medicaid funding in the recently enacted stimulus package is helping to mend a fraying health safety net, according to Ann Kohler, director of the National Assn. of State Medicaid Directors. "Many states were forced to have some pretty dramatic cuts in eligibility that they now will not implement because of the stimulus act."

That's in part because the stimulus requires states receiving extra funds to maintain or restore Medicaid eligibility to July 1, 2008, levels. California Gov. Arnold Schwarzenegger on March 30 signed a bill reducing the state's Medicaid re-enrollment requirement from twice a year to annually. This will allow California to receive at least $8 billion in temporary Medicaid funding increases.

Ken King, the Oklahoma State Medical Assn.'s executive director, said he believes his state, which is facing a $900 million budget deficit next year, would have trimmed all of its state agencies without the stimulus funding. The deficit represents about 12% of the projected fiscal 2010 budget of almost $7 billion, according to state estimates from February. But Kilgore said health care programs do not now appear to be on the chopping block.

Kohler said CMS needs to give more details on how many of the provisions in the stimulus act and CHIP reauthorization will work, such as the CHIP dental coverage.

The Escalating Importance of Clinical Research

In 2004, the National Institutes of Health (NIH) launched its NIH Roadmap for Medical Research, an ambitious plan to delineate the agency’s priorities and to serve as a guide for scientific research in the coming years [1]. Central to this plan is the promotion of clinical and translational research. Since then, the NIH has shifted more extramural funding to these areas and added funding for didactic-degree programs in clinical research at academic institutions around the country to train the next generation of clinical researchers. As part of recent economic stimulus efforts, the American Recovery and Reinvestment Act of 2009 will infuse the NIH with hundreds of millions of dollars, much of it slated for clinical-research endeavors [2].

Opportunities in clinical research abound for medical students and residents. And as the focus of the leading scientific agency in the country shifts more toward research involving human subjects, there is little doubt that increasing conflicts between the agenda of scientific advancement and biomedical ethics will surface. This issue of Virtual Mentor explores a number of these aspects of clinical research.

The three clinical cases in this issue describe scenarios that are particularly salient for medical trainees engaged in clinical research. In the first case, Julie Freischlag explains how to avoid faculty favoritism in recognizing the efforts of a resident who enrolls patients in a clinical trial being conducted by his department chair. The second case commentary, written by Mark T. Hughes, charts the course a research trainee should take when asked to add honorary authors to a scientific publication. Timothy M. Pawlik tackles the thorny issue of how to handle suspected research misconduct in the final clinical case.

This month’s journal discussion and clinical pearl relate to the ethics of statistics. In the former, Garrett M. Sparks reviews a 2008 article from theNew England Journal of Medicine that describes the negative publication bias in studies of antidepressants and its effect on the public’s perception of their efficacy [3]. The clinical pearl by Chandra Y. Osborn focuses on the importance of statistical literacy and explains how to interpret several frequently misunderstood statistical concepts.

As alluded to earlier, the NIH is funding many programs to develop future clinical researchers. In the medical education section, Emily Abdoler writes about some of the opportunities available to medical students and residents and the efforts to ensure that ethics is an integral part of that training. In the medicine and society section, Rebecca Dresser takes up the question of how the NIH determines its research priorities and the ethical considerations that must be part of those decisions.

The medical history and medical narrative sections this month highlight the human side of clinical experimentation. In the narrative section, Amanda Redig interviews participants in human-research studies and explores their motivations for subjecting themselves to pain and possible side effects of treatment, often with no known benefit. In a similar vein, Akhil Mehra writes about the incentives for participation in Walter Reed’s historic yellow-fever experiments in the beginning of the 20th century.

Inherent to the conduct of clinical research in this day and age is the role of the institutional review board (IRB)—the oversight body responsible for the protection of human subjects involved in clinical experimentation. In a two-part policy forum, Margaret R. Moon and Felix Khin-Maung-Gyi explore the role of IRBs and debate the pros and cons of for-profit “central” IRBs and not-for-profit, academic institution-based “local” IRBs. Finally, Micah R. Onixt and Robyn L. Sterling review the liability and scrutiny that IRBs face when adverse events do occur in the course of clinical research.

I would like to thank all the distinguished authors for their contributions to this month’s issue of Virtual Mentor. In addition, many thanks are owed to the staff at the American Medical Association—Audiey Kao, Faith Lagay, Phil Perry, and Jennifer Schooley—for their creative input, editorial efforts, and administrative support. It is our sincere hope that you enjoy reading about the aspects of clinical-research ethics covered in this issue and that you find it challenging and educational.

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References

1. National Institutes of Health. NIH roadmap for medical research. 2009. http://nihroadmap.nih.gov. Accessed March 13, 2009.
2. US Department of Health and Human Services, National Institutes of Health. NIH challenge grants in health and science research (RC1). 2009. http://grants.nih.gov/grants/funding/challenge_award. Accessed March 13, 2009.
3. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy.N Engl J Med. 2008;358(3):252-260.

Vital Signs When Stubbornness in a Physician Nearly Proves Fatal

All was aflutter. The sixtysomething Chinese woman squirmed on her stretcher, hands trembling over her chest while her two daughters hovered anxiously. The emergency room din mounted as a note from the patient’s family physician appeared under my nose: “Status post neck sprain x 2 days, complaining of neck pain, bilateral arm numbness, weakness, dyspnea, need to rule out acute cervical disk herniation.”

The patient’s expensive-looking clothes and red hair—set off by loud gray roots—were my first clues. The note reinforced my initial impression: numbness (suggesting damaged nerves) and trouble breathing (suggesting asthma or pneumonia) for two full days? This had to be anxiety.

Trying to keep an open mind, I flipped to the triage nurse’s note. The chief complaint read, “Dizzy, lower back pain, neck pain x 2 days.” No help. Then the woman’s whole body began to shake. Now I wasn’t so sure about my diagnosis.

“Elsa,” I called out to her nurse. “She needs to be out of the hallway and into a room, on a monitor.”

“We’re very full.”

“She needs a room.”

Ten minutes later, translator at my side, I got a second shot. The daughters gathered round. The woman looked calmer as the monitor flashed normal vital signs: blood pressure, pulse, oxygen saturation, breathing rate—all A-OK.

The symptoms had begun while she was making love to her husband two days earlier. Sudden dizziness at first. Then he pulled her to the side, which triggered shooting pain down her arms. How hard had he yanked? Not so hard. Had they been quarreling? (First rule of whodunits: It’s always the spouse.) No. Had the symptoms worsened or changed over the past two days? No. Was she a nervous type of person? No. Any psychological problems? No. Otherwise healthy? Yes—a little high blood pressure, nothing more.

“Do you feel pain anywhere?” I asked, placing my hand on her head. “Here?”

“No.”

Then on her chest: “Here?”

A burst of Mandarin: “My back.”

The daughters piped up. “Her back has been hurting for months.”

“But why is she here today?”

“Dizzy. Very dizzy.”

Aha. Maybe vertigo. “Like the room is spinning?”

“No.” (That would have been too easy; vertigo is common and usually benign.)

“And no chest pain?”

“No.”

“What’s wrong with her?” one daughter wanted to know.

“Beats the heck out of me” would have been the honest answer. To buy some time, I resorted to the Universal Doctor’s Dodge: “We’ll run some tests.”

It had to be anxiety. Those vague, unconnected symptoms could only be psychological. Besides, my patient looked fit as a fiddle. This was classic attention-seeking behavior: The oversolicitous daughters, the dyed hair, the fluttering.

Fifteen minutes later, one of the daughters accosted me in the hallway. “My mother’s numb from the neck down!”

“Not possible,” I almost blurted out. If the spinal cord were compressed enough to cause total body numbness, there should be arm or leg weakness too.

Back in the room, my patient had launched an energetic imitation of Lamaze breathing: puff, puff, puff. “Why is she doing that?” I asked the daughters.

“It makes her feel better.”

It was making me feel worse. Was I missing something? Again I checked the strength in her arms and legs. Normal. Then it hit me: Hyperventilation can cause numbness. This was anxiety.

I found Elsa.

“Let’s give her Ativan (a Valium-like drug), one milligram IV. She needs to calm down.”
I returned to her room and told the family, “This will make her feel much better.” Emboldened by my own decisiveness, I continued, “We’ll get a CT scan of the neck.”

Everyone smiled.

The first doctor had raised the possibility of a bulging disk. The CT scan would appease him and the family. Problem was, getting a neck scan for a presumed neuro­logical deficit meant we had to rule out stroke as well. Otherwise, the radiologists would think I’d lost it.

“And we’ll get a scan of the head,” I added. The smiles widened.
Twenty minutes later, I peeked into the room. The woman lay back, eyes closed. Success. A daughter walked over and whispered, “She has not had the CT scan yet. When?”

“Your mother looks better, doesn’t she?”

She shrugged impatiently.

“Soon, soon,” I assured her.

A half hour later, working through my backlog of patients, I spied my redhead returning from the scanner. I rang up the radiologist. “Say, Russ, could you take a quick look at this scan? Story is, her husband pulled on her arms two days ago. Claims she’s numb from the neck down, but I’m not convinced. Just tell me it’s normal and we can send her home.”

“Sure,” came the answer. I waited on the phone for a good 45 seconds. Then there was a shout: “She has a subarachnoid!”

“Wha...?!”

“Pull up the head scan. Subarachnoid.”

On the radiology screen in the emergency department, a white blush highlighted gray whorls of brain. “Jesus,” I muttered. “She said it was her neck.”

“It’s a bleed,” Russ insisted urgently.

Subarachnoid hemorrhage springs from a leak in one of the delicate arteries that snake between the brain and the arachnoid membrane, the brain’s cellophane-like covering. The culprit is a berry aneurysm, a slight (one-eighth to one-third of an inch) ballooning of the artery in the circle of Willis, a network of arteries at the base of the brain. When the balloon ruptures, the sudden jet of blood typically triggers a thunderclap headache along with vomiting and loss of consciousness. Smaller leaks, however, may cause only confusion or back pain (which is why emergency physicians see subarachnoids lurking behind every headache or case of the dizzies). Often the instigating event is sudden exertion, like lovemaking. The textbooks, I learned long ago, have a term for this: coital subarachnoid. A classic diagnosis.

Instead of fleshing it out with probing questions, I had let my patient’s squirrelly symptoms and dyed hair throw me off the scent, interpreting each new finding as confirmation of my original bias. I hustled back to the patient’s room and asked the daughters, “When she felt bad that night, did she have any headache at all?”

The family conferred.

We had to hurry. If patients survive the first arterial leak, chances are fearsomely high that a second one, days or weeks later, will kill them.

“Maybe some headache, yes. But it went away.”

“Any vomiting?”

“Once or twice, but then it stopped.”

The nuggets had been there; the doctor just hadn’t panned thoroughly enough.

Everything clicked into place: Hyperventilation lowers pressure inside the skull by constricting blood vessels. The Lamaze breathing had made her feel better. The numbness? Probably due to the blood irritating her brain and spinal cord.

Now we had to hurry. If patients survive the first arterial leak, chances are fearsomely high that a second one—days or weeks later—will kill them.

I pulled the daughters out of the room. And hoped to God I hadn’t come across as dismissive before. “Your mother has blood in her brain. A vessel has burst. She might need an operation.”
They covered their mouths.

“We need to send her uptown immediately,” I said, as we arranged her transport to a hospital with an angiography suite.

The rise of interventional radiology has radically changed the treatment of brain aneurysms. The first step is still an angiogram, in which radiopaque dye is injected into the cerebral arteries so they can be fluoro­scoped—the image appears as black tendrils against a ghostly white background—and the leak pinpointed. In the old days (the mid-1990s), brain surgery came next. A piece of the skull was lifted, the brain burrowed into, and a clip fastened across the neck of the aneurysm. Nowadays, once the angiogram finds the defect, a tiny platinum coil can be threaded up the vessel and into the aneurysm. There, the coil spawns a clot that seals the opening. Coiling, compared with surgery, halves the rate of post-op seizures, according to a study in The Lancet, though it does have a higher rebleed rate.

My patient’s aneurysm bulged off the top of the right carotid artery. The coil went in smoothly and plugged the defect. Some subarachnoid patients have brain artery spasms caused, it is thought, by the irritating effect of blood outside the arteries. Luckily, my patient had none of those. She went home with her daughters, anxiety-free, a few days later.

As for myself, I could only paraphrase an old adage: If you can’t be smart, at least be lucky.
Tony Dajer is chairman of the department of emergency medicine at New York Downtown Hospital in Manhattan. The cases described in Vital Signs are real, but names and certain details have been changed.