Alliances in Human Biology: The Harvard Committee on Industrial Physiology, 1929-1939.

In 1929 the newly-reorganized Rockefeller Foundation funded the work of a cross-disciplinary group at Harvard University called the Committee on Industrial Physiology (CIP). The committee's research and pedagogical work was oriented towards different things for different members of the alliance. The CIP program included a research component in the Harvard Fatigue Laboratory and Elton May's interpretation of the Hawthorne Studies; a pedagogical aspect as part of Wallace Donham's curriculum for Harvard Business School; and Lawrence Henderson's work with the Harvard Pareto Circle, his course Sociology 23, and the Harvard Society of Fellows. The key actors within the CIP alliance shared a concern with training men for elite careers in government service, business leadership, and academic prominence. But the first communications between the CIP and the Rockefeller Foundation did not emphasize training in human biology. Instead, the CIP presented itself as a coordinating body that would be able to organize all the varied work going on at Harvard that did not fit easily into one department, and it was on this basis that the CIP became legible to the President of Harvard, A. Lawrence Lowell, and to Rockefeller's Division of Social Sciences. The members of the CIP alliance used the term human biology for this project of research, training and institutional coordination.

Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association.

Following hematopoietic cell transplantation (HCT), recipients are subjected to extensive genetic testing to monitor the efficacy of the transplantation and identify relapsing malignant disease. This testing is increasingly including the use of large gene panels, which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor can prove challenging. In response to queries from donor registries and transplant centers regarding best practices in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and develop a framework to aid decision making. These guidelines aim to provide recommendations on predonation consenting, postdonation testing of recipients, and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognized that registries will have different access to resources and financing structures, and thus whenever possible, we have made suggestions on how recommendations can be adapted.

Evaluation of Cage Mate-induced Postsurgical Trauma in Mice.

Although mice are social animals, individual housing is sometimes requested after surgery. We questioned whether pair-housing mice after surgery resulted in greater trauma to the surgical site as compared with single housing. We further evaluated the effect of individual housing after surgery on the wellbeing of mice that had previously been pair-housed. Female C57Bl/6 mice (age, 6 to 8 wk) were housed as follows: group A, individually housed before and after surgery (n = 10; all 10 mice underwent surgery); group B, pair-housed before surgery but individually housed after surgery (n = 10; all 10 mice received surgery); group C, pair-housed before and after surgery (n = 20; 10 mice underwent surgery but their cage mates did not); and group D, pair-housed before and after surgery (n = 10; all 10 mice underwent surgery). Dependent variables were body weight, body condition, grimace based on real-time scoring, nest building, time to incorporate into nest test (TINT) score, wound trauma score, and missing wound clips. Weight was significantly different between groups A and C both before and after surgery. Mean nest building scores were significantly higher for pair-housed (groups C and D) than for individually housed mice (groups A and B) after surgery while TINT scores were significantly higher for these same groups both before and after surgery. Mean values for body condition, grimace score, wound score, and number of wound clips missing did not differ significantly between any groups either before or after surgery. Taken together, these results suggest that pair housing mice after surgery benefited their wellbeing but did not increase trauma to the surgical incision site or disturb wound clips as compared with individually housed mice. Furthermore, separating previously pair-housed mice (group B) did not affect these measures as compared with individually housed mice (Group A) either before or after surgery.

Mechanisms of γδ T cell accumulation in visceral adipose tissue with aging.

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age-associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident population which is sustained in aging. Migration of peripheral γδ T cells into VAT was observed at less than 10%, with a decreasing trend by aging, suggesting a minor contribution of recruitment to γδ T cell accumulation with aging. Since tissue-resident T cell numbers are tightly regulated by a balance between proliferation and programmed cell death, we further explored these processes. Using in vivo EdU incorporation and the proliferation marker Ki67, we found that the absolute number of proliferating γδ T cells in VAT is significantly higher in the aged compared to young and middle-aged mice, despite a decline in the proportion of proliferating to non-proliferating cells by age. Analysis of apoptosis via caspase 3/7 activation revealed that VAT γδ T cells show reduced apoptosis starting at middle age and continuing into old age. Further, induction of apoptosis using pharmacological inhibitors of Bcl2 family proteins revealed that VAT γδ T cells at middle age are uniquely protected from apoptosis via a mechanism independent of traditional anti-apoptotic Bcl2-family proteins. Collectively, these data indicate that protection from apoptosis at middle age increases survival of tissue-resident γδ T cells resulting in an increased number of proliferative cells from middle age onward, and leading to the age-associated accumulation of γδ T cells in VAT. These findings are important to better understand how adipose tissue dysfunction and related changes in the immune profile contribute to inflammaging among the elderly.

Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. Methods: NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. Results: Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. Conclusion: Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.

Garrett Hardin's Tragic Sense of Life.

I discuss biologist Garrett Hardin's view of human nature, with examples from the background to his seminal 1968 essay "The Tragedy of the Commons" and his testimony before the US House of Representatives in the 1970s. Hardin saw the human species as being governed by deterministic laws of the same kind that controlled all other forms of life. Humans, as much as cattle and microbes, were in inevitable competition for space and resources. Equal parts Malthusian political economy and Cold War systems science, his view was the survival of the human race depended on obeying these iron laws. Human freedom was the recognition of-and obedience to-its nature. This determination for humanity to act within the strictures placed on itself by its own nature was what he called "lifeboat ethics." In order for the citizens of the rich countries to survive, many in the Third World would have to die. In this sense I characterize Hardin's sense of life as tragic, both as a play on the title of his famous essay, and to emphasize his view that the problem of human population growth had no 'win-win' solutions.