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An interview with Christopher Hamlin in November 2020 in which he explains how he became interested in the history of public health. He talks about the outcomes of epidemics, the relationship between trust in science and moral imagination, why historians use previous public health experiences to think about the present, the role of discipline and ideology in problem-solving arrangements to deal with public health issues, and his new article on legal medicine. Resumo Entrevista com Christopher Hamlin, feita em novembro de 2020, na qual ele explica como se interessou pela história da saúde pública, fala sobre as consequências das epidemias, sobre a relação entre confiança na ciência e imaginação moral, por que historiadores levantam experiências passadas de saúde pública para pensar a respeito do presente, sobre o papel da disciplina e da ideologia nos arranjos para resolução de problemas de saúde pública e comenta a respeito do seu novo artigo sobre medicina legal.

Growing attention to the philosophy of forensic science in recent decades has sometimes included the question: “what kind of science is forensic science”? Yet there has been little discussion of how that question has been differently construed in terms of period, place, and prevailing anxieties. Following an examination of the unique character this question must have in an American legal context, this article reviews three modes/phases of response, rooted successively in individual authority, comprehensive method, and institutions of flexible problem-solving. The conclusion applies this complex legacy in two ways: first to clarify areas of incoherence and tension in recent attempts to underwrite forensic sciences, and second to supply a fuller framework for Max Houck’s argument for the essentially historical character of forensic science.

In the original version of our article [...]

An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIVsmE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms., We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIVmac251-based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIVsmE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIVsmE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIVsmE660-specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIVsmE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.

Between 1906 and 1909 the biologist Ronald Ross and the classicist W.H.S. Jones pioneered interdisciplinary research in biology and history in advancing the claim that malaria had been crucial in the decline of golden-age Greece (fourth century BCE). The idea had originated with Ross, winner of the Nobel Prize for demonstrating the importance of mosquitoes in the spread of the disease. Jones assembled what, today, we would call an interdisciplinary network of collaborators in the sciences and humanities. But early negative reviews of Jones’s Malaria and Greek History (1909) by classicists and historians ended the project, despite a positive reception among malariologists. Today, the “Jones hypothesis” is often used to exemplify the naivete of past scholarship, and few examine Jones’s evidence and reasoning. In this age of renewed interdisciplinarity, a review of what went wrong is timely. Jones and Ross knew they were opening new methodological territory and struggled with the challenges of multiple ways of knowing. Over 100 years later, malaria remains an important site of historical-biological research, yet integration is elusive. After reviewing the Jones-Ross relationship, Jones’s interdisciplinary campaign, and the reception of the hypothesis among classicists/ancient historians and in malariology, we conclude by highlighting some of the specific challenges faced by those exploring the interface of biology and history.

Background: HIV-1 envelope trimer is a candidate for designing an effective HIV vaccine. Results: gp140 attached to Strep-tag through a long linker is used to purify HIV trimers. Cleaved, uncleaved, and fully and partially glycosylated trimers are characterized. Conclusion: Cleaved and glycosylated gp140 assembles into authentic propeller-shaped trimers. Significance: This system could generate HIV-1 trimers for clinical trials and vaccine manufacture., The trimeric envelope spike of HIV-1 mediates virus entry into human cells. The exposed part of the trimer, gp140, consists of two noncovalently associated subunits, gp120 and gp41 ectodomain. A recombinant vaccine that mimics the native trimer might elicit entry-blocking antibodies and prevent virus infection. However, preparation of authentic HIV-1 trimers has been challenging. Recently, an affinity column containing the broadly neutralizing antibody 2G12 has been used to capture recombinant gp140 and prepare trimers from clade A BG505 that naturally produces stable trimers. However, this antibody-based approach may not be as effective for the diverse HIV-1 strains with different epitope signatures. Here, we report a new and simple approach to produce HIV-1 envelope trimers. The C terminus of gp140 was attached to Strep-tag II with a long linker separating the tag from the massive trimer base and glycan shield. This allowed capture of nearly homogeneous gp140 directly from the culture medium. Cleaved, uncleaved, and fully or partially glycosylated trimers from different clade viruses were produced. Extensive biochemical characterizations showed that cleavage of gp140 was not essential for trimerization, but it triggered a conformational change that channels trimers into correct glycosylation pathways, generating compact three-blade propeller-shaped trimers. Uncleaved trimers entered aberrant pathways, resulting in hyperglycosylation, nonspecific cross-linking, and conformational heterogeneity. Even the cleaved trimers showed microheterogeneity in gp41 glycosylation. These studies established a broadly applicable HIV-1 trimer production system as well as generating new insights into their assembly and maturation that collectively bear on the HIV-1 vaccine design.