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From Neurons to Neighborhoods: Lead Case Studies

Schematic representation of the electron shell structure of the lead atom.

The public health spectrum runs from the invisible to the international. To improve health, researchers need to work every angle—from the intricate ballet of molecules that make humans live or die to the Byzantine process of shaping government policies that affect millions of people. A breakthrough in the lab feeds into new treatment and prevention programs, which in turn can shape national and global strategies.

A classic example is lead. While the human body needs metals like zinc, iron and copper in order to thrive, it has no use for lead. Yet the toxic metal insinuates itself into the human body and the brain, causing special destruction at the fragile edges of human life: in children whose brains are fast developing and in older adults enduring age-related changes. These pages detail the “neuron-to-neighborhood” efforts being made by Bloomberg School scientists to eliminate lead’s danger to health.

Brain Damage
One of the key ways that lead damages the brain remained a mystery until Environmental Health Sciences (EHS) Professor Tomás Guilarte revealed lead’s interference with the NMDA (N-methyl-D-aspartate) receptor, a protein complex on nerve cells that is highly concentrated in the hippocampus and is essential for learning and memory. The insight can help scientists focus their strategies for reversing lead poisoning, says Guilarte, PhD ’80.

The Most Susceptible
Armed with the knowledge that certain genes make some people more likely to absorb calcium, EHS Professor Brian Schwartz and colleagues sought and then discovered genes that affect the absorption and distribution of lead—making some people more susceptible to lead poisoning. “We shouldn’t base regulations on the least susceptible people but the most susceptible,” says Schwartz, MD, MS.

Into the Bloodstream
How does lead reach the brain? Joseph Bressler, EHS associate professor, recently discovered a critical pathway: a protein known as divalent metal transporter 1 (DMT1) that normally transports iron in the small intestine, allowing it to enter the bloodstream. Bressler, PhD, demonstrated that DMT1 can also transport lead.

Paternal Risks
A father’s sperm is lead-free, but EHS Professor Ellen Silbergeld and her team have discovered that lead can subtly disturb the contribution of some paternal genes, resulting in altered gene expression in the embryo that may cause neurodevelopmental disabilities. They have also found that lead inactivates protamine, a protein that protects the DNA in a father’s sperm. “It used to be, we only worried about lead causing paternal sterility,” says Silbergeld, PhD ’72.

Making National Policy
As an assistant administrator at the U.S. Environmental Protection Agency in the mid-1990s, Lynn Goldman, MD, MPH ’81, helped establish regulations for the control of lead in paint, soil and dust in home environments.

Writing New Guidelines
A member of a national panel developing new guidelines for management of adults with lead exposure, Brian Schwartz is helping to shape future federal regulatory policy. Surveying more than a decade of lead research, Schwartz says, “Our findings suggest the current OSHA standards are inadequate to protect lead workers.”

Lead in the Bone
Lead levels in the bone gauge an individual’s lifetime dose and can even predict one’s cognitive future. Brian Schwartz demonstrated that the more lead in a person’s bones, the smaller the total brain volume. “The influence of lead on cognitive test scores is almost as large as age itself,” he says. “We call it ‘accelerated aging.’ ”

When “Safe” Isn’t Safe
In a 2004 study, Epidemiology Assistant Professor Eliseo Guallar, MD, DrPH, found that people who had blood-lead levels at one-fifth the CDC’s “elevated” criterion are still 2.8 times more likely to develop peripheral arterial disease (PAD), a painful condition marked by reduced blood flow to the legs.

Safe Neighborhoods
Centuries of lead paint use and eight decades of leaded gasoline consumption have created “a huge reservoir” of lead in U.S. homes, soil and dust, says Mark Farfel, associate professor of Health Policy and Management. Farfel worked with contractors, community leaders and government agencies in the late 1980s to devise safe, low-cost and effective lead abatement strategies that ultimately led to federal guidelines. Farfel, ScD ’87, is now concentrating on preventing lead’s dispersal when urban buildings are demolished. 

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