Larry Needham and the Partition Ratio
Larry Needham was fearless when it came to analytical challenges. Colleagues at the
CDC had told me to approach Larry for his advice in regard to a tricky problem in the
early 1990s. From my interactions with Vernon Houk and Eric Sampson, I learned that
Larry was emerging as an important person in risk assessment of human exposures to
environmental chemicals. At the time, I had to assess exposures to PCBs in a Faroese
birth cohort. We had found that prenatal methylmercury exposure was associated with
cognitive deficits at age 7 years, but were considering if this could be confounded by
PCB exposure.
Umbilical cord tissue from the births had been collected, but nobody yet had ever
dared analyze PCBs in this medium. Without hesitation Larry said, ‘Send them on, we’ll
do them.’ We agreed that a couple of hundred analyses would be sufficient (and Barry
Johnson agreed that ATSDR would pay the expenses). I soon traveled back to Atlanta
with a very large package of frozen umbilical cords. My flight was delayed, and at 2:30
a.m. I was waiting for my huge styrofoam box at the baggage claim. Virlyn Burse from
Larry’s laboratory met me there. I thanked him for his kindness, but Virlyn said that his
main concern was not me, but the precious samples that Larry was eager to secure in the
CDC’s freezers. Virlyn did carry me as supplementary cargo and dropped me at my hotel
before rushing onward with the cords.
Once the analyses were done, we discussed the validity of chemical
measurements in different sample types. How does PCB partition into the various body
compartments? Experimental studies supported the notion that PCBs would distribute
throughout the lipid phase, and that tissue concentrations would depend mainly on the
lipid content. For the lipid phase, the partition ratio would then be close to 1. However,
there was little empirical evidence from humans to support this notion.
We had to do a study of partitions between matched samples from childbirths. So,
we developed detailed sampling criteria and procedures for sample preparation, and my
colleagues in the Faroes agreed to provide the samples. At CDC, Don Patterson, Andreas
Sjodin, Wayman Turner, and Antonia Calafat helped to run the analyses.
It was a large group effort, with over 80 different analytes in sample sets of
maternal serum, cord serum, placenta, cord tissue, and milk. The final manuscript was
somewhat delayed, but Larry saw it through. The published article (Needham et al.,
2011) received much attention, though sadly, by that time, Larry had passed.
While working on the paper, we discussed compartment theory in a more general
sense. The body of science can be looked upon as a large number of different
compartments that are interlinked to a smaller or greater extent, with fractional transfer
rates representing the information flow between compartments. Similar to persistent
pollutants, information accumulates within each compartment, and the partition ratio
reflects the extent to which this information is shared.
I pictured Larry and his laboratory in a large central compartment, where
exposure assessment methodology and experience were developed to a much greater
extent than anywhere else in the world. More importantly, Larry’s compartment had the
wonderful attribute of high transfer rates for information passed on to colleagues in other
compartments. The partition ratios would be close to 1. But in contrast to slow-moving
PCBs, the data and advice were transferred from Larry and his colleagues rapidly and
generously, independent of media and affinities.
Larry was a giant in exposure assessment research. From the point of view of
compartment theory, Larry’s legacy is magnified by his enthusiasm for collaboration and
his willingness to share. Larry had a catalytic effect on environmental health research: In
science, a partition ratio close to 1 makes a world of a difference.
Reference
Needham LL, Grandjean P, Heinzow B, Jørgensen PJ, Nielsen F, Patterson DG Jr, Sjödin
A, Turner WE, Weihe P. Partition of environmental chemicals between maternal and
fetal blood and tissues. Environ Sci Technol 2011; 45: 1121-6.
Philippe Grandjean
Department of Environmental Medicine, University of Southern Denmark, 5000 Odense,
Denmark
Department of Environmental Health, Harvard School of Public Health, Boston, MA
02215, USA