Loose dry ice is handled on Nov. 11 at the Dry Ice Nationwide manufacturing facility in Reading, England. (Leon Neal/Getty Images)
On Monday, the pharmaceutical company Pfizer announced early data that showed a vaccine it has been developing in partnership with the German drug manufacturer BioNTech was more than 90 percent effective in preventing covid-19. This level of efficacy amazed researchers, including those at my own institution, Yale School of Medicine, who agreed that if the data holds (it has not yet been peer reviewed), then this vaccine would be poised to dramatically curtail the impact of the virus.
This news made headlines, along with Joe Biden’s and Kamala D. Harris’s rollout of a covid-19 task force composed of biomedical experts, suggesting even as the number of daily new infections reached an all-time high in the U.S., a cure was in sight. But, storing and distributing a vaccine — especially the potential Pfizer vaccine, which must be frozen until use at -70°C, around the temperature of dry ice — poses a significant challenge.
Rural cattle breeders offer a solution. In the 1950s, during the Cold War, they played a major role in developing and scaling up the technology to circulate biological materials globally at temperatures as low as -196°C, that of liquid nitrogen. In what is known as the “cold chain,” these supply networks made it possible to ship temperature-sensitive agricultural and medical products within and beyond the United States.
In other words, practices honed in the American heartland helped make cold-dependent therapeutics feasible — from organ transplantation to blood banking, artificial insemination to vaccine development and distribution. The history of how cattle breeders developed and supported a worldwide cold chain demonstrates that problems of global public health require attention to technology transfer between industrial sectors, such as agriculture and biomedicine, as well as between nations.
One of the most influential early players in this network was American Breeders Service (ABS). Founded in 1949 in Madison, Wis., by entrepreneur Rockefeller “Rock” Prentice, the company also sponsored the American Foundation for the Study of Genetics, a not-for-profit corporation devoted to the science of animal breeding. The ability to freeze bull semen contributed to an intensification of reproduction, making it possible to get thousands rather than dozens of calves from each sire.
Within four years of its founding, ABS had recruited experts in the emerging field of cryobiology, known as the “science of frosty life,” to demonstrate the potential of using cold storage to manipulate the breeding process. In 1953, it celebrated the success of their experiments in artificial insemination using frozen bull semen with the birth of a calf they named “Frosty,” and a promotional film declaring this to be “Progress, progress the American way!”
The next step was to hone the ability to keep sperm cold as it traveled between the lab and various farms. The need to improve mobile cold storage — a crucial link in the cold chain — had become imperative. Traditional kerosene gas refrigerators — which were quickly becoming obsolete — were portable, albeit cumbersome. Liquid nitrogen presented a new possibility. It was inert and nonflammable, making it safe for the materials it kept frozen as well as the field technicians transporting them.
Working together with engineers at the Linde cryobiology lab near Buffalo, ABS developed a mobile cold-storage canister that combined both a new insulation material and a vacuum to support liquid nitrogen. The biologics contained inside could be maintained for up to two weeks, enabling it to be “transported from farm to farm as the local inseminator made his rounds.”
Though ABS had invested heavily in the development of this technology, it did not seek a patent, allowing competitors to gain access. Prentice recognized that making their equipment freely available would accelerate broader innovation necessary to extend the cold chain globally. The result was a transformation in both the cattle breeding and liquid nitrogen industries.
By the 1970s, the liquid nitrogen-based distribution system developed by ABS had been endorsed by the World Health Organization (WHO), which was deeply invested in developing systems of blood-based epidemiological surveillance of infectious diseases. While this required accumulating and freezing blood samples from people living all over the world, existing modes of cold storage were either too expensive — in the case of dry ice and freeze drying — or unreliable — in the case of wet ice.
Liquid nitrogen circumvented these problems. The container ABS had built was adapted for use in shipping biologics other than sperm. In one pilot project conducted by the WHO, the “refrigerator-transporter” was filled with liquid nitrogen in Europe and then sent to Lagos, Nigeria, where it was transported to more remote rural areas where human blood samples were being collected before being shipped back to Europe. The whole process took two weeks and represented a dramatic strengthening of the cold chain for public health.
A cattle breeding company — in partnership with corporations interested in the production of low temperature gases — had become the source for knowledge on practical considerations of working with cryopreserved materials, as well as suppliers of equipment to those wishing to preserve and transport other kinds of biological materials on an industrial scale.
The connection between vaccination demands and agriculture is not new. In fact, the word vaccination comes from the Latin for cow. The first vaccines were developed on dairy farms in the late 18th century, inoculating humans with cowpox as a means of preventing the spread of smallpox.
It would take until 1980 for smallpox to be declared eradicated. Part of what made the mass distribution of smallpox vaccine possible is that it was heat stable, meaning that it did not need to be refrigerated.
In the age of covid-19, the history of cattle breeding in the Midwest provides insights about the challenges and possibilities involved with the distribution of Pfizer’s potential vaccine, whether it ultimately uses liquid nitrogen or another mode of cold storage. In fact, how agricultural workers and engineers partnered with public health officials the world over at mid-century, during times of geopolitical strife, provides precisely the kind of unexpected object lessons necessary for surviving the present.
