When In Doubt, Lead It Out

An ancient Roman lead glazed Skyphos.

For centuries historians have marveled at the architectural feats of the Roman empire. Its inhabitants engineered sprawling road networks, constructed monumental coliseums, and channeled millions of gallons of water through their aqueducts. But beneath this splendor was a dependence on heavy metals that is thought to have contributed to the unraveling of Rome’s dominion over the West. 

Lead was an ancient engineer’s bread and butter. It is extremely malleable, ductile, and is known to have an incredibly low melting point. These properties allowed blacksmiths to shape and weld lead into waterproof structures. Silver is the chemical byproduct of lead mining but in the context of ancient Roman metallurgy, lead was the economic byproduct. It sounds counterintuitive but the primary economic drive for mining galena ore (PbS, lead sulfide) was the acquisition of silver for Roman currency (the denarius). Through a process called cupellation, the lead-silver alloy was heated so the lead oxidized into litharge (PbO) and separated leaving behind trace amounts of silver. Afterwards, the litharge was heated and reduced with galena (smelting) to recover metallic lead. 

An image simplifying the cupellation process.

Rome’s silver mining industry was so massive that lead became remarkably cheap, abundant, and accessible. The Romans used it in various aspects of life, with the lining of their plumbing systems being the most memorable example. In fact, our modern word “plumbing” comes directly from the Latin word for lead, plumbum. In addition to architectural purposes, lead was molded into pots, jars, pans, and utensils. So although lead is remembered for its structural utility, its unique properties proved to be indispensable in the culinary realm, particularly in Roman winemaking.

When lead comes into contact with the natural organic acids found in grapes, it undergoes a chemical reaction that produces lead acetate Pb(OAc)₂. This compound, referred to as the “sugar of lead” and “salt of saturn”, registers as sweet to human tastebuds. Roman cooks exploited this chemical reaction by boiling down unfermented grape juice in lead cauldrons to create a thick, syrupy concentrate called sapa. What they didn’t realize was that they had just poisoned thousands of their fellow citizens. This toxic syrup was poured into expensive wines to enhance their flavor, disguise poor agricultural vintages, and act as a preservative to delay unwanted fermentation.

The consequences of this exposure were devastating. Since lead ions look and behave similarly to helpful minerals like calcium and iron, the human body cannot detect them. When ingested, the body absorbs the heavy metal, allowing it to cross the blood-brain barrier and once it does, there is little that can be done to remove it. Once lead enters the central nervous system, it acts as a powerful, irreversible neurotoxin, destroying neurons and disrupting vital cellular enzyme synthesis, a condition called plumbism, better known as lead poisoning.

A calcium ion (left) beside a lead ion (right).

The primary target of lead toxicity in the body is an enzyme called ALAD (aminolevulinic acid dehydratase). Without functional ALAD, the body cannot synthesize heme – the core component of hemoglobin that allows red blood cells to carry oxygen. As a result, consumers of sapa most likely developed lead-induced anemia. For the average Roman citizen (pleb), plumbism manifested as abdominal cramps, severe joint pain, and reproductive failure. The patricians (upper class), who could afford high quality lead-lined plumbing and drank an estimated two liters of wine per day faced rampant infertility, miscarriages, kidney failure, erratic behavior, and paranoia. 

When the brain wants to send a signal, it floods the synapse with calcium, triggering the release of neurotransmitters like glutamate, which is essential for cognitive function. Lead being introduced to the blood brain barrier completely disrupts this process. As lead competes against calcium at binding sites, it initiates a toxic accumulation of intracellular calcium. This damages the mitochondria by opening the mitochondrial permeability transition pore (mPTP). Once this pore opens, the mitochondrion is susceptible to collapse, swelling, a halt in energy production, and eventually cell death. Mitochondrial dysfunction can (and often does)  result in neuron-killing excitotoxicity characterized by a leak of glutamate. 

The prefrontal cortex is responsible for cognition, decision making, and emotional regulation. The disruption of neurotransmitter synthesis in this area of the brain can trigger irritability, paranoia, hallucinations, and cognitive decline. Interestingly, Rome’s most infamous rulers developed these traits once they came into power. Rome’s “mad” emperors – Nero and Caligula – consumed sapa-sweetened wine, like most Roman aristocrats. Although their erratic behaviors and paranoia could be attributed to character traits magnified by a  proximity to unchecked power, plumbism is also considered to be a plausible cause of their antisocial demeanors.

Aside from the brain, lead exposure crippled the rest of the anatomy of Rome’s citizens as well. Throughout Rome’s dominion, citizens complained of excruciating abdominal pain, historically dubbed “lead colic.” Calcium helps release acetylcholine, which dictates the contractions of smooth muscle found in the stomach and intestines. When lead replaces calcium, acetylcholine leaks from nerve terminals and locks the intestines into violent spasms.

An individual with a stomachache.

Additionally, the kidneys were also severely affected by the ingestion of lead. As they filtered the tainted blood, lead molecules built up inside the tubules, forming dense clumps that scarred kidney tissue. Eventually the filters (nephrons) died, leading to kidney failure. As the kidneys failed, they could no longer excrete uric acid. Instead, the uric acid accumulated in the bloodstream, crystallizing within the joints. This disease was known to many European civilizations as the “disease of the rich” though we refer to it as gout today.

Ultimately the story of Rome and lead presents a profound irony. The same characteristics that made lead a pillar of civic progress were the exact traits that turned lead into a seemingly innocuous sweetener that physically crippled Rome’s citizens. We currently inhabit a world where new synthetic chemicals, and artificial foods are created every day. Instead of waiting until we fall ill to these modern toxins, we must recognize that perceived progress is often the detriment of human biology and that history has shown us that we must quit while we’re ahead.