June 10, 2005

Therapeutics
Delivery Technology Paves Way for RNAi Therapies

Neuroscience
Gene Clue to Brain Asymmetry Revealed on Right Side

Social Medicine
Gun Violence May Be Viewed as Contagious

Neurology
Fetal-cell Transplants Reverse Parkinson’s in Two Patients

Clinical Research
Discord Found in Clinical-trial Contracts

Health Care Policy
National Mental Health Survey Shows Mixed Results on Progress

Genetics
Disease Mutation Tracked Down, Ending ‘Curse’ for Colombian Families

New Books
The Spring Bookshelf

Education
HMS Teaching Awards Presented for 2005

Accolades
Students Laud Gardner as Champion of Humanism in Medicine

Medical Ethics
Debate at HMS Frames Ethics of Online Organ Donation

Brain Chemical Serotonin Linked to Left–Right Patterning of Embryo

Rising Leaders in Minority Health Research Turn Data into New Directions

New Chairs Honor Federman and Egan Family

Honors and Advances

In Memoriam

Let Consumers Drive Progress in Health Care Quality

Front Page

Brain Chemical Serotonin Linked to Left–Right Patterning of Embryo

Image courtesy of Michael Levin Serotonin gradient in the early frog embryo. This cross section of a frog embryo at the 32-cell stage reveals the asymmetrical distribution of serotonin, the red arrow showing its presence and the white its absence.

The neurotransmitter serotonin, a small-molecule messenger known primarily for its role in signaling at the synapse between nerve cells, has been implicated in an early stage of patterning the left–right axis in vertebrate embryos. It is the first endogenous neurotransmitter to be described in the developmental pathway regulating the asymmetric positioning of internal organs.

Working in embryonic chicks and Xenopus frogs, two models with very different early architectures, researchers led by Michael Levin demonstrated the role of serotonin prior to the emergence of embryonic nerve cells and characterized the pathway in which serotonin is active. Appearing in the May 10 Current Biology, the findings further establish that serotonin is, indeed, present in very early chick and frog embryos, the function of the serotonin pathway is needed for normal asymmetry, and its activation occurs prior to asymmetric gene expression. The study sheds light on the role of small, nonprotein molecules in embryonic patterning and on the evolution of synaptic signaling mechanisms.

“This work demonstrates that a signaling mechanism previously believed to exist only in neuronal synapses is, in fact, also a signal used by communicating primitive embryonic cells—thus illustrating a fascinating reuse of cellular control systems in evolution,” said Levin, an HMS assistant professor of oral and developmental biology at HSDM and the Forsyth Institute and an associate member of the staff at Forsyth.

Though the study finds parallels between the role of serotonin in frogs and chicks, differences also exist. Serotonin-based signaling takes place during cell cleavage stages in frogs and early gastrulation in chicks. Whether early left–right patterning mechanisms involving the neurotransmitter also exist in mammals is controversial. No early mechanisms are yet known to be conserved between mice and other species, for example. Yet this study raises the possibility that the serotonin pathway plays a role in left–right embryonic patterning in mice and other mammals, including humans.

One important clinical ramification of serotonin-based patterning in human embryos would be the danger to fetal development posed by pregnant women taking antidepressant monoamine oxidase inhibitors like phenelzine (Nardil), believed to block natural enzymes that break down serotonin. But if the role of serotonin in human embryonic development were definitively established, opportunities would also arise for the targeted development of drug therapies to correct errors in the serotonin pathway, thereby preventing fetal malformations.

—Robert Neal

Rising Leaders in Minority Health Research Turn Data into New Directions

Photo by Steve Gilbert In presenting infant mortality data from racial and ethnic groups in Massachusetts, Jacqueline Grant said that an analysis focusing on discrete periods of risk before and after birth might reveal different health improvement strategies for different groups.

Though the 2003 infant mortality rate in Massachusetts was lowest among the states, the rate for individual communities and racial and ethnic groups in the commonwealth showed wide disparities. In fact, some of the disparities among these groups were greater than those among communities. The findings were part of a fellowship project by Jacqueline Grant, who presented her research on May 5 during the 2005 annual meeting of three HMS programs in minority health policy based at the Office for Diversity and Community Partnership. Grant reported that the 2003 infant mortality rate for non-Hispanic blacks in Massachusetts was 12.7 per 1,000 live births, three times the 4.1 mortality rate for non-Hispanic white infants. This rate among Hispanics was 5.6.

These figures represent widely varying trends in infant mortality. The commonwealth experienced a 31 percent reduction in infant mortality from 1990 to 2003. In that same period, non-Hispanic blacks underwent only a 7 percent reduction, but Hispanics had a 39 percent reduction and non-Hispanic whites a 33 percent reduction.

To clarify primary directions to further reduce these rates, Grant recommended the Perinatal Periods of Risk approach advocated by CityMatCH, a national maternal and child health organization. The technique would map feto-infant mortality among different racial and ethnic groups into four risk periods from maternity to infancy, revealing the stages of highest comparative risk. “When the feto-infant mortality rate for each component is compared, the differences in their weighted distributions suggest that each group would need to examine different strategies to reduce their overall feto-infant mortality rate,” Grant said.

The teen birth rate, which is associated with infant mortality, also showed variation by community as well as race and ethnicity. While this rate for whites was 13.7 births per 1,000 young women aged 15 to 19, the rate for blacks, 40.3, was three times higher. And for Hispanics, the rate of 78.3 was nearly twice the rate of blacks. Despite these gaps, the teen birth disparities among communities exceeded these disparities among racial and ethnic groups, with Holyoke (91.9), Lawrence (82.9), and Springfield (79.3) having the highest teen birth rates.

The annual meeting was marked by this sort of eye-opening analysis, prompting speakers to comment on the “environment of innovation” and the “exciting time” for their health policy research. Practicum presentations like Grant’s were given by the fellows and scholars of the Commonwealth Fund/Harvard University Fellowship in Minority Health Policy and a complementary program, California Endowment Scholars in Health Policy at Harvard University. The two days of talks also included those by alumni fellows of the Commonwealth Fund/Harvard program, faculty fellows of the HMS Center of Excellence in Minority Health and Health Disparities, and a keynote address on each day.

The annual meeting was marked by this sort of eye-opening analysis, prompting speakers to comment on the “environment of innovation” and the “exciting time.”

In her practicum presentation, Alexy Arauz, a fellow in the Commonwealth Fund/Harvard program, gave evidence for the ability of patient assistance programs offered by pharmaceutical manufacturers to decrease drug costs at community health centers. Fellow Ivette Motola (HMS instructor in surgery at Brigham and Women’s Hospital) argued for the use of remote simultaneous medical interpretation via headsets worn by the clinician and patient to aid in interpretation for non–English speaking patients. And California Endowment scholar Richard Nunes presented a case for increasing mental health services to offenders in the juvenile justice system, who are disproportionately members of racial and ethnic minorities.

Starting the second group of practicum presentations was Commonwealth Fund/Harvard fellow Christian Arbelaez (HMS instructor in medicine at BWH), who worked with the Association of American Medical Colleges in determining that a significant proportion of the increase the association recommends in the physician workforce over the next 10 years should be made up of minorities. California scholar Barsam Kasravi explored the structure of New England foundations and their grants for easing racial and ethnic disparities in health care. Working along similar lines, fellow Lenny Lopez (HMS instructor in medicine at BWH) studied whether academic hospitals provide higher quality care for congestive heart failure and found it was not consistently better. He plans to investigate whether Latinos have adequate access to care for congestive heart failure and other conditions.

Unmet dental needs in a California immigrant community was the research topic of scholar Abraham Nobel, who found that providing patients with care is not the problem, “getting them into the dental chair is the issue.” Back on the East coast, fellow Jacqueline Nwando Onyejekwe, analyzed support for school-based sexuality education in Lynn, Mass. Early results showed that a large majority of parents and other adults in the town believe that sexuality education should be part of the school curriculum.

In his keynote on the opening day of the conference, president of the California Endowment Robert Ross considered the national disparities agenda. He said that good health is a resource, not an ultimate goal, and that the majority of what determines health status is not medical, but social and political.

Giving the second day’s keynote, Garth Graham, deputy assistant secretary for minority health in the Office of Minority Health of the U.S. Department of Health and Human Services, said the take-home message on leadership in minority health is that “at the end of the day, it’s all about change.” The annual meeting was sponsored by the HMS Office for Diversity and Community Partnership, headed by the dean for diversity and community partnership, Joan Reede.

—Robert Neal

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