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The following was delivered as an invited 5 minute talk during a panel session at the High Blood Pressure Research Council of Australia Winter School. The panel was addressing diversity and inclusion in hypertension research. This is not an area I am an expert in. But whatever our role or standing in society, we can reflect on our contribution to diversity and inclusion. I’m ashamed to say that reflecting on my research activities to date I am not making much of a positive contribution. But I have identified ways to change.

Talk transcript

I want to preface this talk by saying do as I say, not as I have done in the past. If you look over my past publications, you will see a strong male sex bias in my animal studies. And if you were a subject in my human studies, you will have seen me address sex, but not gender.

So, if you will indulge me, I’m going to reflect on why I have been a laggard when it comes to diversity and inclusion in basic science research. Perhaps we can all learn from my mistakes.

Let’s start with animal studies…

Cell studies

Actually, let’s start with cell studies. I have not reported on sex in publishing our cell studies. And I have not investigated if there are differences in the sex of the source of the cell line for our studies. Every mammalian cell has a sex signature. The idea of precision medicine should start at this basic level of investigating if there are sex differences in our hypothesis at the cell level. I’m not an expert when it comes to cell work, and I imagine there are challenges in sourcing commercial identical cell lines of male and female sex origin. But that only points to a pressure that should be applied to companies. If we are generating our own cell line we should be looking at both male and female derived lines. As a bare minimum, we should report the sex of the derivation of the cells in publication. Currently, of the few cell work papers that do report on sex, 30% of cell lines are female derived.

Animal studies

That is not as bad as the situation in animal studies. Around 15% of animal studies are in female animals. This is actually getting worse with time. In the early 90’s, around 35% of studies were in female animals. Some particular diseases such as multiple sclerosis and osteoporosis go the opposite way with poor representation of male animals, even though the disease affect both males and females. These, though, are the few exceptions to the male dominated world of animal studies.

So why are we… or perhaps I should speak for myself… why have I historically used only male animals in most of my studies. I would guess that I am always looking for the most efficient way to run studies. Removing variables makes a study more efficient. If we were to assume that females are the same as males, then we can reduce the time and cost of a study theoretically by around a half. But why are the majority of researchers choosing to study male animals and assuming them to be the same as females, rather than studying female animals and assuming them to be the same as males?

There is the perception that because of a monthly hormonal cycle, female animals have a greater variability in what ever parameter we study. And greater variability means more animals to have a suitably powered study. In the hypertension world, there is good evidence of cardiovascular changes corresponding to the oestrous cycle. But there is no good evidence that this introduces more variability in the data than is observed in male animals. We have to remember that animals, even inbred, are all different. Variability is inherent. Our assumption that female animals may introduce more variability does not hold weight.

Talking of variability between animals, let’s address gender. Animals have behavioural and social traits that can be interpretted as an expression of gender. Such personality and social representation will effect cardiovascular variables. I’m not saying we should study gender in animals… though it may be an interesting topic for an eager investigator to explore. It is a tricky area to research in the literature as many people use the terms sex and gender interchangeably. It would be very helpful, and much more respectful of non cis-gendered people, to refer to the sex of an animal when addressing male or female as designated by chromosomes.

As an interesting aside, the gender of the investigator also has an impact on animal studies. Rats and mice with a male investigator tend to show inhibition of pain and stress compared to when they are with a female investigator. In a very quick search of the literature I was unable to find anything on investigator gender effects on cardiovascular measurements in animal studies. It would be fair to assume that if investigator gender effects animal stress, then there would be cardiovascular effects as well.

Human studies

So, now we have moved a little into humans, let’s address human studies in basic research. Let’s skip over the fact that we should be looking at both sexes in all our studies. Even in small basic research studies that should still be feasible and part of the recruiting strategy and planned analysis. Something that we don’t address in basic cardiovascular human research is gender. I have no doubt that gender has a role in cardiovascular health. Many gender diverse people live happy healthy lives. But as a minority that is discriminated against, people in the LGBTQI+ community are disproportionally burdened with poorer mental health. This has cardiovascular implications.

Most of our basic research is not powered to study gender. But if you are running a study of size, it should be an included variable. In smaller studies, I would propose that asking our study participants their gender before asking their sex is an inclusive way to conduct our studies. Even if you are not going to use gender as a study variable, it allows the study investigator to approach the question of sex with a non-cis-gendered person in a more inclusive way. If you want to be even more pro-active, you could introduce yourself with your gender pronouns. If that is a bit too forward for you, writing the pronouns of the study investigators listed on the participant information and consent form would be another way of showing people that your lab is a safe and inclusive space.

The key messages

I have covered a lot of ground in such a short time. To highlight the main points and areas where I myself need to improve…

  • There is a lot of progress to be made in cell studies. I should be studying both male and female origin cells. Reporting the sex origin of my cell line when publishing findings would be a minimal start.
  • When conducting an animal study, I should study both male and female animals. No excuses.
  • I should use the term sex when I mean the animal or person has a male or female chromosome. I should use the term gender if I have asked the study volunteer their self-representation, or in animal studies have studied animal behaviour.
  • In human studies, even if I am not studying gender, I should ask the study volunteer their gender and place it in their study record. It is the start to an inclusive attitude toward someone that has kindly volunteered to help out in my study.

Bibliography

Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011 Jan;35(3):565-72. doi: 10.1016/j.neubiorev.2010.07.002. Epub 2010 Jul 8.

Caceres BA, Streed CG Jr, Corliss HL, Lloyd-Jones DM, Matthews PA, Mukherjee M, Poteat T, Rosendale N, Ross LM; American Heart Association Council on Cardiovascular and Stroke Nursing; Council on Hypertension; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Stroke Council. Assessing and Addressing Cardiovascular Health in LGBTQ Adults: A Scientific Statement From the American Heart Association. Circulation. 2020 Nov 10;142(19):e321-e332. doi: 10.1161/CIR.0000000000000914.

LGBTIQ+ Health Australia. Snapshot of Mental Health and Suicide Prevention Statistics for LGBTIQ+ People. 2021 Oct.

Klein SL, Schiebinger L, Stefanick ML, Cahill L, Danska J, de Vries GJ, Kibbe MR, McCarthy MM, Mogil JS, Woodruff TK, Zucker I. Opinion: Sex inclusion in basic research drives discovery. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5257-8. doi: 10.1073/pnas.1502843112. Epub 2015 Apr 20.

Plevkova J, Brozmanova M, Harsanyiova J, Sterusky M, Honetschlager J, Buday T. Various aspects of sex and gender bias in biomedical research. Physiol Res. 2020 Dec 31;69(Suppl 3):S367-S378. doi: 10.33549/physiolres.934593.

Radio Health Journal. Gender Diversity in Basic Research. 2015 Oct.

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