Unraveling Radiation's Secrets Through the Million Worker Study and the Mallinckrodt Chemical Works Cohort
Imagine a world where the first atomic bomb wasn't just a historical event but an ongoing scientific mystery—one that would take nearly a century to unravel. In the early 1940s, as the Manhattan Project raced to develop nuclear weapons, thousands of American workers began handling radioactive materials with little understanding of the long-term health consequences.
Today, a landmark scientific effort called the Million Person Study (MPS) is investigating a crucial question: what happens to human health when radiation exposure occurs gradually over years rather than in a single instant? At the heart of this inquiry lies the Mallinckrodt Chemical Works cohort, a group of St. Louis workers who processed uranium for the very first atomic reactor and whose health experiences are now providing unprecedented insights into radiation's effects on human health 4 6 .
Their story represents one of the most important and prolonged public health investigations in American history, bridging past discoveries with future protection.
When most people think about radiation risks, they picture the atomic bomb survivors of Hiroshima and Nagasaki. While these studies provided foundational knowledge about acute high-dose radiation, they left a significant gap in our understanding: what are the health effects when exposure happens gradually over time, as occurs in occupational, environmental, or medical settings? 5 8
The Million Person Study was specifically designed to address this question by examining the health outcomes of American workers and veterans exposed to radiation throughout their careers 5 .
The scale of the MPS is unprecedented—it's approximately twelve times larger than the Japanese atomic bomb survivor study and includes diverse occupational groups from Department of Energy workers to nuclear power plant employees, medical radiation technicians, and atomic veterans 8 .
This extraordinary cooperation enables scientists to pool data and resources in ways that were previously impossible, creating a rich dataset for answering critical questions about radiation protection.
The Mallinckrodt Chemical Works in St. Louis, Missouri, holds a singular place in nuclear history. In 1942, Arthur Holly Compton, director of the Metallurgical Laboratory at the University of Chicago, recruited this established pharmaceutical company to process uranium for the Manhattan Project 4 .
The challenge was enormous—the project required 40 tons of uranium oxide and 6 tons of uranium metal to initiate the world's first controlled nuclear reaction. Within just eight months, Mallinckrodt produced the uranium needed for Enrico Fermi to create the first human-made sustained nuclear chain reaction on December 2, 1942, marking the birth of the atomic age 4 6 .
Mallinckrodt begins processing uranium for the Manhattan Project
First sustained nuclear chain reaction using Mallinckrodt uranium
Uranium processing operations move to Weldon Spring, Missouri
Mallinckrodt plant closes
Behind the scientific data are real people—the 2,514 White male employees who form the core of the Mallinckrodt cohort study 4 . These workers, predominantly hired in the 1940s and 1950s, performed their duties with limited understanding of the potential long-term health risks.
The cohort is notable for its long-term follow-up—84% of the workers have been confirmed deceased, providing substantial data for mortality analysis 4 .
One of the most challenging aspects of the Million Person Study has been reconstructing credible radiation doses decades after exposures occurred. For the Mallinckrodt workers, this meant accounting for six different sources of exposure: external gamma rays from radioactive elements, medical X-rays from required chest examinations, internal intakes of uranium measured through urine samples, radium intake through radon breath measurements, occupational exposures at other facilities, and cumulative radon concentrations in the work environment 6 .
Researchers employed sophisticated biokinetic models to estimate how radioactive materials moved through workers' bodies and deposited in specific organs 4 . The mean lung dose for Mallinckrodt workers was calculated at 65.6 mGy, with a median of 29.9 mGy 4 .
| Method | Workers Monitored | Purpose |
|---|---|---|
| Film badge records | 2,514 | Measure external gamma radiation |
| Occupational chest X-rays | 2,514 | Account for medical radiation exposure |
| Uranium urinalysis | 1,868 | Estimate internal uranium intake |
| Radon breath measurements | 487 | Measure radium intake |
| Radon ambient measurements | 1,356 | Assess workplace radon concentrations |
| Silica dust estimates | 1,317 | Evaluate non-radiation toxin exposure |
Determining the health status of a cohort over 70 years requires remarkable detective work. For the Mallinckrodt study, researchers used multiple data sources including the National Death Index, Social Security Administration Epidemiological Vital Status Service, and state mortality files to confirm vital status for 99.4% of workers—an exceptionally high follow-up rate that lends credibility to the findings 4 .
The third mortality follow-up of Mallinckrodt workers, published in 2024 and following workers through 2019, revealed several important patterns. Perhaps most notably, researchers observed more brain cancer deaths than expected compared to the general U.S. population 4 . The standardized mortality ratio (SMR) for brain cancer was 1.79, meaning there were approximately 79% more brain cancer deaths than would typically be expected 4 .
79% more brain cancer deaths than expected in general population
Risk approximately doubles at 100 mGy kidney dose
| Health Outcome | Finding | Statistical Measure |
|---|---|---|
| Brain Cancer | Increased compared to general population | SMR: 1.79 (CI: 1.14-2.70) |
| Kidney Cancer | Increased with radiation dose | HR at 100 mGy: 2.07 (CI: 1.12-3.79) |
| Lung Cancer | No association with radiation | HR at 100 mGy: 0.93 (CI: 0.78-1.11) |
| Cardiovascular Disease | Increased with heart dose | HR at 100 mGy: 1.11 (CI: 1.02-1.21) |
| Non-malignant Kidney Disease | Associated with high dust exposure | HR: 3.02 (CI: 1.12-8.16) |
An important finding from the recent Mallinckrodt analysis was the positive relationship between radiation dose and cardiovascular disease 4 . The hazard ratio at 100 mGy was 1.11, indicating an 11% increase in risk at that dose level 4 . This finding contributes to growing evidence that radiation's effects may not be limited to cancer but might also include other chronic conditions.
The findings from the Mallinckrodt cohort and the broader Million Person Study have direct implications for radiation protection programs that impact worker safety, cleanup criteria for contaminated sites, medical practice, and energy production policies 8 .
The study provides crucial evidence for evaluating, developing, and implementing science-based guidance that protects those who work with radiation while allowing beneficial uses of nuclear technology to continue 8 .
Surprisingly, the Mallinckrodt cohort has relevance that extends beyond Earth's atmosphere. NASA is particularly interested in the workers' exposure to radium, which deposited in their brains and released high-LET alpha particles 6 .
This provides the only human analogue, though limited, for understanding potential effects of galactic cosmic rays—high-energy, high-Z particles that astronauts would encounter on extended Mars missions 6 .
The Million Person Study is specifically examining nuclear submariners because they share unique similarities with astronaut crews: sleep deprivation, fatigue, disruption of circadian rhythms, confined spaces, isolation, and protracted radiation exposures 8 .
| Research Tool | Function in the Study |
|---|---|
| Medicare/Medicaid Claims Data | Provides information on smoking histories, disease occurrence, and cognitive impairment |
| Virtual Pooled Registry Cancer Linkage System | Offers high-quality cancer incidence diagnoses |
| Comprehensive Epidemiologic Data Resource (CEDR) | Houses decades of occupational radiation data |
| Colossus Software | Open-source R-based software to handle billions of data points |
| Biokinetic Models | Estimate how radioactive materials move through the body and deposit in organs |
| National Death Index | Provides accurate cause of death information |
The story of the Mallinckrodt workers and the Million Person Study embodies the saying that "the past is prologue to the future." These workers, who contributed to one of the most significant scientific achievements of the 20th century, continue to advance our understanding of radiation health effects nearly eight decades later.
As the Million Person Study continues, with researchers working to complete data harmonization and ultimately pool all cohorts into one comprehensive analysis, we face both promise and challenge. The vision is for a National Center for Radiation Epidemiology and Biology that would maintain this invaluable resource for answering questions we haven't yet thought to ask 8 .