The role of advocacy in sustaining male contraceptive research and development.

Novel male contraceptives have been in development for well over half a century, and despite a robust predicted global market for new methods, funding for research and development has been extremely limited. While the pharmaceutical industry previously supported male contraceptive research and development, industry partners are only spectators in the current space, awaiting a product that has been de-risked by the public sector before re-entering the field. Current male contraceptive development efforts are thus primarily funded by nonprofit, non-governmental, and government agencies who also act as the primary advocates for the field. Specific organizations include the International Consortium on Male Contraception, the Population Council, the Male Contraceptive Initiative, the World Health Organization, and the US National Institutes of Health. The funding provided by these public agencies, alongside their social and policy-based advocacy efforts such as market research, public education, and calls to action have kept the male contraceptive product development space afloat, resulting in a pipeline of potential products advancing towards market approval. However, as these products mature into more expensive clinical stages of development, they continue to face significant funding challenges, which many programs may not overcome. To fully realize the benefits of novel male contraceptive options, it is incumbent on philanthropic entities, impact investors, venture capital, and/or the pharmaceutical sector to provide significant and timely support for male contraceptive research and development.

Catalyzing momentum in male contraceptive development†.

Globally, nearly half of all pregnancies are unplanned. Male contraceptives offer the potential to decrease unintended pregnancy and introduce contraceptive equity, but decades of research have yet to bring a novel product to market. New funding avenues from the philanthropic sector seek to stimulate research in male contraceptives through investments, grants, and support for trainees alongside other programs that encourage product development and ultimately commercialization. This Forum outlines the purpose of and funding opportunities provided by Male Contraceptive Initiative, a funding agency and non-profit focused on the advancement of non-hormonal, reversible contraceptive technologies for those who produce sperm.

The role of team science in the future of male contraception†.

Efforts to develop a male contraceptive method beyond condoms and vasectomy have been on-going for nearly 70 years. During this time, there have been ebbs and modest flows of resources available to support product development, but not at a level sufficient to carry research efforts through to market. The small community of researchers that have continued to pursue the development of male contraceptives is comprised of dedicated scientists who have a great deal of knowledge and experience to offer. While collaboration has been an organic outcome of limited resources, competing research objectives and geographically diverse locations have made consistent and sustained progress challenging, particularly for those working in the earliest stages of developing nonhormonal, reversible male contraceptive methods. While the past decade has seen an increase in funding to the field, the levels are still modest when placed in the context of actual costs to bring products to market. In addition, there are challenges still to be identified given that there is no regulatory precedent for these products. These challenges present an excellent use case for the application of design-thinking or human centered design, as a means of generating novel solutions. By engaging those with deep technical expertise in the field of male contraception as well as thought leaders from other fields of practice, design-thinking offers an opportunity to identify potential strategies, including nontraditional approaches, capable of driving the product development process forward, in a faster and more efficient manner.

Does size matter? Comparison of body temperature and activity of free-living Arabian oryx (Oryx leucoryx) and the smaller Arabian sand gazelle (Gazella subgutturosa marica) in the Saudi desert.

Heterothermy, a variability in body temperature beyond the normal limits of homeothermy, is widely viewed as a key adaptation of arid-adapted ungulates. However, desert ungulates with a small body mass, i.e. a relatively large surface area-to-volume ratio and a small thermal inertia, are theoretically less likely to employ adaptive heterothermy than are larger ungulates. We measured body temperature and activity patterns, using implanted data loggers, in free-ranging Arabian oryx (Oryx leucoryx, ±70 kg) and the smaller Arabian sand gazelle (Gazella subgutturosa marica, ±15 kg) inhabiting the same Arabian desert environment, at the same time. Compared to oryx, sand gazelle had higher mean daily body temperatures (F(1,6) = 47.3, P = 0.0005), higher minimum daily body temperatures (F(1,6) = 42.6, P = 0.0006) and higher maximum daily body temperatures (F(1,6) = 11.0, P = 0.02). Despite these differences, both species responded similarly to changes in environmental conditions. As predicted for adaptive heterothermy, maximum daily body temperature increased (F(1,6) = 84.0, P < 0.0001), minimum daily body temperature decreased (F(1,6) = 92.2, P < 0.0001), and daily body temperature amplitude increased (F(1,6) = 97.6, P < 0.0001) as conditions got progressively hotter and drier. There were no species differences in activity levels, however, both gazelle and oryx showed a biphasic or crepuscular rhythm during the warm wet season but shifted to a more nocturnal rhythm during the hot dry season. Activity was attenuated during the heat of the day at times when both species selected cool microclimates. These two species of Arabian ungulates employ heterothermy, cathemerality and shade seeking very similarly to survive the extreme, arid conditions of Arabian deserts, despite their size difference.

Variation in the daily rhythm of body temperature of free-living Arabian oryx (Oryx leucoryx): does water limitation drive heterothermy?

Heterothermy, a variability in body temperature beyond the limits of homeothermy, has been advanced as a key adaptation of Arabian oryx (Oryx leucoryx) to their arid-zone life. We measured body temperature using implanted data loggers, for a 1-year period, in five oryx free-living in the deserts of Saudi Arabia. As predicted for adaptive heterothermy, during hot months compared to cooler months, not only were maximum daily body temperatures higher (41.1 ± 0.3 vs. 39.7 ± 0.1°C, P = 0.0002) but minimum daily body temperatures also were lower (36.1 ± 0.3 vs. 36.8 ± 0.2°C, P = 0.04), resulting in a larger daily amplitude of the body temperature rhythm (5.0 ± 0.5 vs. 2.9 ± 0.2°C, P = 0.0007), while mean daily body temperature rose by only 0.4°C. The maximum daily amplitude of the body temperature rhythm reached 7.7°C for two of our oryx during the hot-dry period, the largest amplitude ever recorded for a large mammal. Body temperature variability was influenced not only by ambient temperature but also water availability, with oryx displaying larger daily amplitudes of the body temperature rhythm during warm-dry months compared to warm-wet months (3.6 ± 0.6 vs. 2.3 ± 0.3°C, P = 0.005), even though ambient temperatures were the same. Free-living Arabian oryx therefore employ heterothermy greater than that recorded in any other large mammal, but water limitation, rather than high ambient temperature, seems to be the primary driver of this heterothermy.