Speaking of science: Emerging international trends in sex and gender science with Dr Cara Tannenbaum

For the November edition of Speaking of Science, NHMRC was joined by women’s health specialist and Professor of Medicine at the Université de Montréal in Canada, Dr Cara Tannenbaum.

Dr Tannenbaum discussed the evolution of sex and gender in science, how they exist on a spectrum and how they interact because no matter if you’re enforcing best practice or you’re growing science, improving care for everyone with sex and gender science depends on you!

Listen to Dr Tannenbaum ‘Speak of Science’ and delve into the new and emerging international trends in sex and gender science and the lessons learned to advise on best practices to benefit all Australians.

Recorded on Tuesday 26 November 2024 from 11:00AM – 12:00PM AEDT.

Video transcript

0:00 Prue Torrance 
Thank you for joining us for the seminar today. Just a little bit of housekeeping about our seminar series. We are recording this session, and it will be posted to our website afterwards. There will of course be an opportunity for Q&A at the end and multiple modes of Q&A for people online.

You'll be able to use the chat, and we may be able to also do the hands up for you to ask. We'll come to that at the end, and I do have a small audience in the room in Canberra with me as well, who may ask questions from in the room. But first, let's get to the topic of today's seminar.

Welcome to this very special edition of our Speaking of Science series on emerging international trends in sex and gender science.

It's excellent timing for such a discussion, with NHMRC and the Department of Health and Aged Care having recently released the NHMRC-MRFF Statement on Sex, Gender, Variations of Sex Characteristics and Sexual Orientation in Health and Medical Research.

The Statement takes into account the fact that health and medical research provides the evidence base that informs our healthcare, and by giving greater consideration to sex and gender diversity in research, we aim to improve the evidence base and provide higher quality and safer healthcare for all the individuals in our community.

To our speaker, I am pleased to welcome Doctor Cara Tannenbaum all the way from Canada as our guest speaker for Speaking of Science today.

Cara is a women's health specialist and a Professor in the Faculty of Medicine at the University of Montreal in Canada.

From 2015 to 2022, she served as the Scientific Director of the Institute of Gender and Health at the Canadian Institute of Health Research, CIHR, Canada's national health research funding organisation.

In this role, she implemented Canada's Sex and Gender Based Analysis Policy, which raised the integration of sex and gender and health research grants from 20% to 90% and impressively, we hope to copy.

She has since advised the European Commission, the US National Institutes of Health, the UK's Wellcome Trust and the Bill and Melinda Gates Foundation on similar integration and innovation strategies for incorporating sex and gender and research into patient care. We're taking great advantage of her time in Australia to get her advice here.

She is currently visiting Scientific Director of the Canadian Institute of Gender and Health in Australia as a Distinguished Fellow of the George Institute and a Thinker in Residence at Deakin University in Melbourne.

Today she will be sharing the lessons learned internationally and provide advice to us on what best practice might look like. I can't think of a better person to do that for us.

So please join me in welcoming Dr Cara Tannenbaum to speak on the emerging international trends in sex and gender science.

2:42 Dr Cara Tannenbaum
Thank you so much.

What an absolute pleasure to be here.

Canada and Australia have a lot of similarities and one of those is that we clearly both care about sex and gender.

What I would like you to reflect with me on as I go through the talk today is emerging international trends in the fields of what I'm going to call sex and gender science, new methods in sex and gender science, and then how you, whoever you are, can apply a sex and gender lens in your work, research, practice, programs, teaching or services.

We're going to start with a question and the question is, do sex and gender mean the same thing? And can they be used interchangeably in research?

I'm just going to let people know that I'm having a bit of trouble with the slide moving over here. There may be another way to do it.

But while I wait for somebody to fix the slides, I'm going to ask you, true or false, do sex or gender mean the same thing?

You could write in the chat true or false.

Can those terms be used interchangeably in research?

Come on, folk, I see there's a lot of you online.

Can you type in the chat true or? Oh, good, OK, I see some false is coming in. That's great.

So actually, it sounds like we have a very savvy audience.

So how, how did you do that? Oh, I have to do it here. OK, thank you.

You're right, the answer is false. The terms sex and gender are not interchangeable and should not be used interchangeably in research.

When you say sex, and you could correct other people, I do it all the time. You could ask people here. When you say sex, we will be referring in research to the biological attributes, and we'll be referring to genes or physical features or anatomies or hormones.

When you say gender, you're going to be referring to socially constructed roles that definitely include gender identity, but also include norms and expressions and gender biases in our healthcare system.

Now, if you are a basic scientist, and even if you're not, what I usually say is can you please raise your right hand and repeat after me?

I solemnly swear, folks in the room say it, on the scientific method that I will never again refer to the gender of animals until mice are able to communicate their preferred pronouns.

All right, good. We've got that sorted.

Now let's talk about why biological sex is important. Well, biological sex is important because I don't know, do you have 23andMe here?

Everyone knows that we have 23 sets of chromosomes and 22 of those look the same and are autosomes. But then we have one set, and you'll notice that I'm not saying pair because for many individuals it's not XX or XY, it could be XXY or XO.

Chromosomes that just don't look, they're not the same size and they're not the same shape and that's super interesting because until 2013, the machine that did genomic wide studies couldn't handle chromosomes that weren't the same size.

The sex chromosomes were excluded from all genome-based research before 2013. Which just means do you know how much we don't know?

Because the X chromosome is large, it has 1669 genes and I'm sorry for those of you who have a littler Y small chromosome that only has 426 genes. It definitely leads to different expressions of disease and health among folks with different chromosomes.
What's super cool is that we don't want those with XX chromosomes to get a double dose of all the genes, so one of them gets inactivated. But because some people say women could go rogue, but I'll just say some of those X chromosomes can be a little, you know, they have an attitude and some of them escape inactivation.

That escape probably contributes to some of the disease phenomenon that we see that separate the sexes. So that's kind of interesting.

Here's another true or false question for you. A little harder. Come on, audience.

Oestrogen is a female hormone, and testosterone is a male hormone only. True or false?

I'm waiting for folks online. Oh, I'm not going to be able to teach anyone anything today. OK, yeah, you're right. I'm not even going to wait any longer.

The answer is false. Oestrogen is not a female hormone. Testosterone is not a male hormone.

You'll see the lines on the graph showing that, you know, depending on where we are in our life course, both everyone has testosterone and oestrogen and that the levels fluctuate according to whether you're just born or puberty or menopause or andropause or everyone who goes through everything.

So good, you know that.
Now, why are genes and hormones important? I'm going to give you the example of lung disease.

A lot of people, have you heard if you have a premmie boy, a premature infant, who's a boy, that they're more likely to have respiratory distress syndrome or that their lungs don't develop as quickly as the girls and they'll probably end up very sadly, I have a lot of friends unfortunately in the ICU because of the hormones and everything, boys don't develop their lungs as quickly as girls.

But then after birth, even though young boys get more asthma, their lungs actually go on to grow and develop and be larger than girls. Then starting at puberty, it's girls that start getting more asthma. Look at all these changes that are a combination of genes and hormones, and so that by the time they're adults, there's actually quite a lot of differences in male and female lungs. I'm not speaking to a thoracic society today, so I won't go through them, but even the shape of the lungs just pyramidal in males and prismatic and females.

I want you to remember this because I'm going to give a case study later where I'm going to ask you about something that might happen and what you have to look out for if you work in a hospital because of these kind of differences.

Let me say a few words about gender. Gender is multidimensional.

I know most people when they think about gender, they think about gender identity, which we know is a self-identified sense of self, it’s masculine, feminine, both, neither in between. We say cisgender if the sex that was recorded at birth matches how you feel. We say transgender if it doesn't. But there's also non-conforming and non-binary.

But then there's the roles and relations that I talked about, which are societal expectations. So, you know, could be gender bias in healthcare, it could be about who makes the decision. We always talk about, you know, gender equality in government, but who's really at the top? Who's making the decision and does that affect, I don't know, what gets funded?

For instance, now a picture says 1000 words, at least in Canada. Things are changing for sure. But gender is still socialised from an early age, and this really changes based on culture, too. Different cultures will have different perceptions of gender rules, and that can have an effect.

But in science, you asked me to speak today about emerging trends. While this may be a strange concept to some of you, we're moving away from the binary. Even sex, we no longer will be talking about males and females. We'll talk about sex along a spectrum where there may be variations in sex characteristics, just like gender, just like gender identity exists on a spectrum as well as gender expression. What you can do in science is talk about spectrum thinking rather than binary thinking, which is reflected in our society.

Now, should you think exclusively about sex and exclusively about gender?

Well, you should be precise in the elements of both that you're researching, but it would be too simplistic to say that they don't interact, because sex and gender do interact in society, which will add complexity. Here's an example.
You probably heard about the male crash test dummy, right? Since cars were invented, someone made the decision that the crash test dummy that all cars should be tested on should be the average or the 50th percentile male.

Well, of course that was changed, but only two years ago, believe it or not, that they put in place the first female crash test dummy and of course it has an effect. Because, so the decision was made from a gendered perspective, but the anatomy is actually sex so that's where sex and gender would interact here.

Of course, we now know from epidemiologic studies that because females have wider hips and they have bigger chests and sometimes they're pregnant and on average they're shorter, that female drivers, even when wearing a seat belt, have a 47% increased risk of serious injury compared to male drivers. This is an example of how sex and gender interact.

Other impacts of sex and gender bias is the belief that females historically were just too messy to be included in research, right? They cycled, they had hormones, they menstruated, they got pregnant. So that would kind of complicate the experiment, right and it was probably better not to do research on female animals. Then this belief was exacerbated with a thalidomide scare that some of you may remember from the 1960s where women who were pregnant took a nausea medication, anti-nausea medication that wasn't tested in women, in especially not pregnant women, and very tragic a lot of the infants were born with malformations.

But the result of all this is that, you know, females were excluded from research.

So maybe that makes sense, but where's my audience? True or false?

Female animals are intrinsically more variable than males due to their estrous cycle, making them generally less suitable for baseline scientific models.

Please type in the chat and those of you in the room can say false, really? I mean you don't think. I mean what do you think here? Think true. I've got some truth. I see a lot of people hesitating. They feel like it's a leading question. But all right, all right.

Males shows just as much variability as females. So that is the correct answer.

This is only in the last five years. The two meta-analyses have found that for most applications, female mice and rats are no more variable than male.

A lot of things in science go back to evolution, right? Believe it or not, when the female mice are in the same cage, a lot of species do this, that the females start cycling together. It's like a collaborative group and a commune and things start to become less variable.

But the males, when you put just the males in the other cage so nobody gets pregnant, that alpha male testosterone competitive structure and the animal kingdom comes out and that we now know that there's just as much variability in the male traits is their own female traits, not the same traits, but in general, the overall variability is the same.

Mythbuster! Tell that to folks who do research.

Let's go back to why this is important and what happened.

In Canada, we introduced, like the statement that you talked about here that's being introduced, we introduced it a while ago and folks started including both XX and XY cells in the research. Everyone thinks, oh, stem cell research, yeah, just any stem cell is the same stem cell, but it's not actually because it has 23 sets of chromosomes, 1 is going to be different and that might lead to different results.

This is research from a researcher in Canada who looked at chronic pain. Pain is an issue, and he was doing it and believe it or not, when he looked, because if you look, you will find because nobody ever looked at completely different cells, T cells in female mice and microglial cells in male mice were the communicators in the spinal cord that transmitted the pain signals to the brain. Wow, right?

I mean, maybe one day they'll be completely different medications and that's why female pain maybe isn't well treated. I don't know. I'm just saying we already know that some companies have started marketing their medications for different doses of medications for men and women.

In fact, one of the stories that I like the best is this research they did in the US where believe it or not, they thought one day there may be a shortage of vaccines if something like a world crisis happened. Yeah, I know, very great.

They actually did research. They said, well, let's try with the flu vaccine what if we have to give that vaccine out against also just, you know, micro warfare. They found out that giving half the dose of the flu vaccine to women yielded the same result with less side effects.

I wonder why during COVID, why don't we take that research, and we can actually divide the vaccines in half. There's a lot of good stuff that could happen if we start looking at this and applying it in our research.

But of course, historically, they didn't do this, and the result is that as of a few years ago, most of the research on cells was in males. Even today, mostly on male animals, human trials, clinical trials, there were more men and of course we treat– do you know that the world thinks that women still is a vulnerable subgroup? Even though because women live longer, we make up 51% of the population.

Of course we end up treating more women who live longer. At age 85, you have 2.5 women to one man just because of differences in life expectancy in Canada. Is our research really reflecting the care that we need to be giving in the hospital?

I was telling this story to the CEO here that in the United States, between 1997 and 2000, ten drugs were withdrawn from the market, and they did an audit that found out that eight of these medications pose greater health risks for women than men and my question to you is, do you think that it was because of sex or because of gender?

I'm going to let you write in the chat.

Do you think the drugs were withdrawn because of sex, biological factors or because of gender?

Most people are saying sex. I do ask a lot of trick questions. My students really don't like me, Dr Tannenbaum’s questions are too hard. OK, so I'm getting one gender. None of you have said the right answer yet, because the answer is both, so the answer is both.

Some of the medications that were withdrawn, for instance, if you've heard of the Fen-Fen appetite suppressants, they cause the same valvular heart disease in men and women, but only women were taking them back in the day, right? Because of gender, because of the need to be skinny and societal pressures. That was actually gender because disproportionately women were taking them.

But then there was the stuff that was attributable to sex. Some of the medications like Seldane, which was an allergy medication that some of you may remember for reflux, what they do is they prolong your QT interval, which you could see. The electrocardiogram is kind of like the way the heart beats and women naturally have just a longer tendency. Our heartbeat's a little bit different, believe it or not and these medications, affected women, cause fatal arrhythmias and they die.

Because they weren't tested, people die. We need to take sex and gender into account in health and medical research and of course, recognising that they interact.

Now, that's going to be complex, because it's not like we figured everything out. Are there any epidemiologists online? You're going to love this graph. Don't worry if you're not an epidemiologist. It just shows kind of the differences in disease prevalence or proportion of people who have different disease.

If I say Parkinson's disease, do more men or more women get it? You know, more men. If I say autoimmune conditions like multiple sclerosis, more women get it, right. But why? Why? How have we been funding research for so long and look at these huge differences and we don't know why.

Because I'm a women's health specialist, I always kind of divide it up into when we think about treating diseases, we need to treat diseases that are sex specific or in women's case unique to women and those are bikini medicine, a lot of stuff like under the bikini, right.

Then stuff that's disproportionate to women, like to say migraines. How come with like my mom we assumed, oh, she has a migraine in her bedroom for three days Dad makes dinner. Sorry, gender roles there, but that's the way it was in my house. Like, why?

Why do we just accept that, you know, women are going to take more days off work? That doesn't make sense, and the treatments are the same as they were so many years ago, right?

Then there's conditions that affect people differently. Here you can think of heart disease. You've probably heard that men have crushing heart pain and women don't really get that crushing heart pain. They'll get more fatigue and sweating, more subtle. Why?

That's where our funding, so focus on the mechanisms and by focusing on mechanisms, maybe we'll come up with better treatments.

This is essentially what the journals are saying. Some of you may have heard of the journal Cell. It's a really big journal on basic science and they dedicated an issue this year to sex and gender science and said, I don't even want to hear about male and female cells. If you haven't done that by now, then get with the game. What I want to hear about is, are you looking at the genes or are you looking at the hormones? Or are you looking at that X inactivation escape that I talked to you about so that we could figure out the why and that's really what's going on internationally right now.

Nature just came out with an issue, and kudos to your Australian researchers. We had Sue Hobbs, you know, from the new Centre of Sex and Gender and Equity and Health and Medicine here in Australia, along with Cheryl Carcel and Robyn Norton, they got published so yay Australia!

Saying, this is going to be complicated sorry, but that reductionist 20th century paradigm of science that we all learnt in school it needs to switch to a 21st century complexity paradigm in science. It's going to be hard, but they're going to look back at us in history and like history of science and talk about when there was that shift and that's happening now. We expect you, when you submit your papers, to be up to that level of quality, rigour and integrity in science.

Not just even the reproducibility crisis, right? Some of you may have heard of the reproducibility crisis in science where you took one experiment in one lab and brought it to another lab and then they couldn't reproduce the same. It's because maybe you had a different mixture of male and female cells. Maybe you didn't include female cells. Maybe, you know, if you don't even report what you're doing, how are we supposed to reproduce that?

This is an example of how you might, remember we talked about asthma and why is it more common in males before puberty but then after puberty it's more common in females and especially during pregnancy– my friend's sister died of asthma during pregnancy, she was actually scared to take the steroids even though they were safe because we didn't really test safety in pregnancy so big problem in our world, right?

Is it due to sex factors or is it due to gender factors? Is it maybe some of the exposures that you get because of those gender roles and boys playing in the sandbox or I don't know what. Again, these are changing, but for the most part, people who've grown up, grew up with a lot of the stereotypes in place.

How do we think of exposures and epigenetic processes over centuries because of those? Genetic and stereotypical, Well, not genetic, but stereotypical plays and exposures and occupations. It's something to think about when you're thinking about sex and gender science. Think about what's the source of variability, if you want to talk in scientific language, is it genetic? Is it hormonal? Is it anatomical? Is it due to gender related exposures? This is the kind of thinking and teaching that we need to be doing.

Like I said, you're going to be held to account. This is, I don't know if the date's on it, August 27th, 2024. JAMA letting us know that they will be putting out new instructions to reviewers and the new criteria by which they're going to be accepting articles. Who doesn't want to publish in JAMA?

Very similar to the NHMRC statement, so very much in line preparing our research community here to be able to publish in these big journals

I did want to, we'll talk about sex and gender science in terms of single sex studies.

We talked about conditions that, you know, affect men and women only. In conditions like menopause, why do some women get hot flashes and others don't? This idea of intra group variation, not only sex differences research. The point isn't sex differences research it’s how would you explain it within a group, why there's variable outcomes.

Again, just an example, I won't go through too much detail how it may be biological or maybe it's social, but we need to look at both because as beings we are biological social beings and to not do that then you may be missing something. It is more than just sex differences research.

The same thing with men. At least in Canada, I didn’t look up the statistics here, but men complete more suicides. Are you telling me that men don't have anxiety or men don't get depression? No, that's actually gender bias, right? Because we're not diagnosing them, and a lot of our questionnaires are very gendered. Do you cry a lot? Are you sad? We know that Asian men, for instance, start feeling depressed with stomach pain, but that's not actually in the questionnaire.

By doing sex and gender science, you could benefit everybody.

I was actually telling the story of Paul Cubes, a researcher here in Canada, who was really negative about the concept, and he was studying the immune cells in the liver and how the body gets rid of, have you heard of E coli? That's also traveller disease, but we get it a lot. It's sort of a gram negative bacteria.

He had only, and we know that sepsis is when the bacteria get into your blood and you end up in the ICU from an infection, men actually have worse outcomes. He said, well, I'm going to look at this in males. Then in Canada we forced everyone to consider putting females in their experiments and what he found was that there was this magical antibody in the females that got rid of the E coli way faster than, you know, what was happening in the males.

Then he figured, well, from an evolutionary perspective, females were actually designed to have these antibodies to protect the foetus, and they passed on these antibodies in utero so that when the baby was born, they wouldn't get E coli either from the gut, you could think of how kids come into the world, or just because of what going on.

He was like, wow, should we be making these female antibodies and giving them as a transfusion to men who have sepsis in the ICU.

This is now the way we need to benefit everyone. We have a lot of answers and medicine that are unclear and maybe it's because we never looked. I like to say you may win a Nobel Prize. Paul published in Nature Immunology.

Evolution in sex and gender science is moving from it's a default one size fits all model to oh no, we need males and females, to don't go males, females. It's spectrum thinking, not binary to what is the mechanism to explain the variability that we're seeing.

That is where we are at conceptually, internationally right now in science.

Don't just rush to report the sex difference because you're going to get criticised and also the goal isn't to find a statistically significant sex difference, it's to really make a difference in the clinical world

How do you do that? Well, one, know your literature. Folks have been funded around the world. There's probably something out there that you don't know about, so I'm expecting everyone who's a researcher to go do in your discipline a good literature review to find out what's known already. There are some really good instructions out there how to do this.

Two, appropriately operationalize and measure. If you think sex is relevant in basic science, then look at your cells, tissues, animals. What are you looking for? Don't just, oh yeah, I will include them. It's not about a gender balance sample, number one, gender's the wrong word and number two, I just told you that balance isn't the point. The point is to be able to find out the mechanism.

If you're nervous, we have these in Canada. You know, students are brilliant, right? We've developed actually a Sex and Gender Trainee Network in Canada. We're like, you have to take sex and gender into consideration. We're like, duh, we know that, but can you explain the methods a bit more? Because this is what our supervisors aren't necessarily teaching us because they didn't learn it in school either. There are these two-page method sheets that are available online. How would you measure and manipulate sex hormones and laboratory animals? There's a lot of resources out there.

I've seen these brand-new models of, it's called the 4-core genotype models for people who do animal research to be able to tell if it's the genes versus the hormones by creating new strains that have these manipulations. Again, I won't go into too much detail, but you would be amazed at the different methods that are available out there that folks are using here in Australia too already.

Step three, design an inclusive sampling strategy, and I mean inclusive now for humans. Now we're talking about human participants, it's really important to include all sexes and genders. If you're worried about something in one population or a population that's been understudied, either because of their gender or their sexual orientation, and over sample that group.

Step four, if you're conducting research with human participants, be precise about what aspect of gender you're interested in. Is it gender identity? Is it that gender bias? Gender rules? And have a hypothesis about it. We’re good, you know, my statistics professor told me, Cara, don't just run the analysis, tell me what you're looking for. Let’s not give up hypothesis-driven science just because all of a sudden, we have to include people. What are you looking for? Make your sampling strategy appropriately.

Then once you include people, you're going to want to collect the data. Here I put up the Australian ABS standard. We don't just write are you male, female anymore. We ask what was your sex recorded at birth? How do you describe your gender? Were you born with a variation of sex characteristics? If I understand correctly, this is what's going into the census now here in Australia. In order to link data sets, researchers need to update how they're collecting data for their research.

Again, you know, don't just think gender identity, think other aspects of gender that you can measure that may affect health.

In Canada, we started asking, could a sex difference be partially explained by gender? In fact, one of our researchers, Louise Pilot, who's a cardiovascular researcher, by creating a composite gender score that took different aspects of gender into consideration, was able to show that the poor outcomes experienced by young folk having an early heart attack, if they didn't do well after the heart attack, it was more explained by gender than by sex, which was kind of like, wow.

What does that mean? Independent of sex, gender was more predictive of maybe stress. Where now, she's now going with her hypothesis looking at cortisol testing to see if stress might be a gender-related variable in some instances independent of sex.

Alright, getting into the weeds, but my point is that if you've now included both sexes, but you continue to pull the data, then you're going to miss important findings. Anyone reviewing, anyone going to a student presentation or a faculty presentation, if you see a graph that's not differentiated, you're going to ask, did you desegregate the data?

There are training modules online for this that are freely available. These are the ones from Canada, but the US also has one, the European Commission has. I know that there's some training modules here in Australia, more I think for healthcare, but you can learn more about this.

As we look to the future, you know, there's a lot of stuff coming down the pipeline. We're actually trying to move away from animal research. Have you heard of human organs on a chip? Have you heard of 3D printed organs? This is the way we're going to be doing research in the future. I was a little bit bothered I guess to find a 2017 analysis of 40 non-reproductive organ on a chip technologies where 60 or 2/3 of them did not specify like what cells they were using. Just because it's the future, doesn't mean that it's not going to replicate the mistakes of the past and we're going to need to correct that.

Had a little chat about artificial intelligence or predictive computer modelling. I used to think that, oh, yeah, it's not always applicable. Don't worry, if you're just studying proteins, you don't really need to think of sex. But actually, did you know that the 3D model of proteins is different based on whether it was produced from RNA from a cell with XX or XY chromosomes? So like, wow.

Even the 3D models of protein and how much of it might be different, or in Canada we had problems with implants, like for breast implants and mesh implants, I don't know if you had that here for women. Well, they were tested in bioengineering companies, but they didn't put hormones in the fluid that they tested them in. So of course, when they put them in human bodies, it wasn't designed for a female environment.

We need to be thinking about this for cardiac stents and then artificial intelligence. There's a lot coming out in the literature that the artificial intelligence is trained on data, but is the data representative of everyone? Is the data accurate? Will there be mistakes in the results that come out if you're not putting in a representative sample of the data that's accurate? Just for you to think about.

Finally, for those of you doing research, you want to make sure there's appropriate sample size. Do you need to all of a sudden double your sample size? No. There are different ways. You may want to be exploratory, maybe have a little sample first to become hypothesis driven. Start by disaggregating, detect main effects, and then obviously you have a big sample, you'll need effect modification and interaction by sex. Don’t know how many statisticians we have on the line, but just doing a shout out to you that there's a lot written on this and you could find out more.
Then of course, there's the problem of OK, I've measured gender, OK, I've included non-binary and trans folk in my study. OK, you know, I've included groups, queer, lesbian, black women, you know, I've been very inclusive and I'm just throwing that as an example. But now I have.

All right. Commercial break over back to our regularly scheduled programme. I wanted to wrap up with a bit on clinical care because I know that there might be folks in the audience who maybe have been a patient or maybe who work in the healthcare system.

How does this apply to you? What we're talking about internationally is this idea to change the way we think about folks going to get care. I was changing the position. Nobody ever taught me these cognitive steps, which we're hoping will now be taught to healthcare providers in school.

One, someone might walk in and maybe you look like a woman. But because I told you, and I'm going to go through a few cases that both sex and gender are important, maybe identify the patient's sex and gender in the administrative record. Then you should be thinking, or if someone comes in as a male with abdominal pain, you don't think that they could be pregnant. They look like a man, right? But they might have a uterus. This idea of sex and gender, I think is very important. We know that there's been cases where ectopic pregnancies have been missed in trans men, so super important to think about.

Recognise sex differences and clinical manifestations of disease. I certainly wasn't taught sweating, fatigue, weakness, malaise in a woman, think heart attack. I wasn't taught that. But we need to start thinking about that because we know now that it's different.

Same with our diagnostic testing. We used to think that treadmill testing was accurate for everyone. But as it turns out, remember I showed you that women's heart rate features on the EKG were a little bit different, it turns out they don't get what we call SD elevation so much, and so it's harder to detect it. We need new criteria. Even when you do the laboratory markers for heart attack, they have a new one called troponin, which measures the amount of heart muscle in the blood that's dying, is a heart attack is you don't get oxygen to your heart. But hey, guess who has a bigger heart and more muscle, males or females? Males, right? I'm saying male sex here, right? The threshold's going to be different, and you might miss it. Just think about this. The medication, should we be giving lower doses.

Then the last one's mitigate gender and racial bias because all this is quite relevant, not just to gender, we're talking about sex and gender today too. But when I think about medical devices and oxygen pulsimeters, and the way an oxygen pulsimeter works is the infrared light goes through the skin and detects the oxygen in the red blood cells. But if you have pigmented skin, it actually absorbs the light, so you don't get accurate reading. I threw in gender and race here just so people know we need to think more inclusively.

But this was a fascinating study from the Cleveland Clinic where they looked at their hospital data variations and quality of care. They found out that if a man or a woman came in with a heart attack, well, the women didn't get kind of the guideline therapy. There's this thing called door to balloon time, which is you walk in the door of the emergency, how quickly did you get into the Cath lab? A balloon opens the artery in your heart.

They found that the 30-day mortality was 6% higher in women than in men. They said, well why, why can that be? Let's look at our protocols. Maybe there's some gender bias in our protocols and they thought about it, and they changed the guideline. They changed the protocol so that they didn't need to say, oh you know, maybe it's a heart attack in the women, maybe it's not.

Let's get the cardiologist. Oh, the cardiologist is on their lunch break. OK, it'll just take a little bit longer. They got rid of some of these steps, and they started everyone on the therapy, even if they weren't sure, and they immediately transferred them and they were able to reduce mortality in women. They closed the gap. They didn't eliminate it, but they closed it to 3% from the minute they walked in till the minute they got their treatment. This is the kind of gender bias and guidelines that we need to start applying based on the evidence if the evidence is there.

In Canada, we've asked our guideline committees, and maybe I don't know if you do that here in Australia yet, to not only make one recommendation or look at the quality of evidence, not disaggregated, but to say is the evidence different for different populations? Should we have different clinical pathways for different populations based on the evidence?

This is a bit of a scary example. We started off with a new way of breathing life into, let's just say science. The lung example, imagine that a trans woman walked in for that asthma case, right?

I don't know and went to get lung function tests. Has anyone ever had lung function tests? You have to breathe into a machine and so a woman does her test. If you assume that it's a woman and that her lungs develop as a woman, then she falls into the female range because there's a different threshold for smaller lungs, which is a good thing. But not if they didn't ask the sex and the gender, the sex recorded at birth, because this woman actually has larger lungs. She was just under diagnosed and sent away and told her that she was normal, and she should have received treatment for her asthma.

These are the harms that come in the hospital if we don't start thinking about this.

Thankfully, a culture shift is underway here. We're really excited about it. If you haven't read the statement, please do.

Then where do you fit in? Are you the person who 95% of you needs to enforce best practices by asking questions, by challenging, by, you know, anyone you know who's doing research or treating patients? If you are a patient, you could ask, hey, has this drug been tested in somebody like me and should I be receiving this dose? That's the new practise and you can enforce it.

Then there are those you who are going to change your research and you're going to grow the science, and you're the ones who, like I say, may win a Nobel Prize, publish in Nature or JAMA, because you're looking at things that we never looked at.

I'll leave you with some questions for reflections. Which elements of sex and gender are most important in your work? How can you improve sex and gender in your own research or practice? How can you encourage others to systematically enhance attention to sex and gender in their work? This is beyond health. This is really for I talked about the crash test dummy, that was industry, right? Anyone in policy, practise, research, teaching, what can you do to become part of our new 21st century complexity paradigm in science that is going to benefit everybody?

I would invite you to be bold and push the boundaries to be the leaders others will follow because improving care for everyone with sex and gender science depends on you. I would invite you to be the change you want to see.

Thank you.

44:37 Prue Torrance
Thank you very much and don't go too far because I am sure we will have questions.

We have ten minutes now for questions, so if you are online, feel free to answer a question in the chat or to raise your hand. Or are there any questions in the room while we're waiting?

Steve, would you like to come up to the microphone?

45:13 Professor Steve Wesselingh
Thanks very much. I mean, it was a terrific talk. I had the opportunity to talk to you earlier, which was fantastic.

You were telling me a little bit about the training programmes that have been developed in Canada. I think Canada is probably a few years ahead of us on this. Did you want to just mention a little bit about those?

45:31 Dr Cara Tannenbaum
A lot of people didn't learn this in school. Doctors, nurses, you know, pharmacists really didn't learn this in school.

In Canada we've developed online training materials and over the years, because we started asking applicants who applied for funding to what we have the equivalent of the NHMRC.

Do you take sex into account in your research? Yes, no, please explain.

Do you take gender into account in your research? Yes, no, please explain it, if not, tell us why not.

A lot of folks started having questions about how to do it properly. This was a new area for them and also, we started asking our evaluators to say whether they thought there was appropriate integration. I think here in Australia you have a statement; you've told people what you expect and it's just a matter of good quality science and rigour and reproducibility.

The evaluators start saying, can you like, I have a question about this. A lot of people use the word gender instead of sex or, you know, I don't really understand the sex and activation thing.

What we did is we did two things. We have the free online training modules, and there was a link in the chat I can put it back up, or you could just go to Canadian Institutes of Health, Research Institute of Gender and Health, look up Learning. We created a YouTube video. If you go to a YouTube, any of you are on the computer, just put sex and gender peer review YouTube and there's a 4-minute video that goes through kind of things that you need to take into consideration.

On the website we also have like what makes integration a strength with criteria? What makes integration a weakness? When is it non-applicable? There are tools online for that.

We made it mandatory actually for our peer reviewers to take a shortened training module so that there would be quality feedback to the applicants once they started including this.

The NIH has training modules also for free. I think you have to register, but it's for free. The NIH training in the US goes more into what are the differences in diseases. I think the Canadian one more is about research.

If you're in the non-medical field, non-health field, then if you're in front of your computer and you type in Stanford University gendered innovations, that was a method case study website that the European Commission funded that has case studies in marine biology and agriculture and industry and all aspects of health research from basic science through to systems biology.

There's a lot of education out there. I don't know if we're thinking of doing more here. There's the new Centre for Sex and Gender Equity in Health and Medicine, which I know is able to provide resources and they're creating an inventory of experts. You might want to become very friendly with somebody who knows what they're doing if you don't do it yourself. Does that answer your question?

48:44 Dr Cara Tannenbaum
I think there might be a comment or a question here online. Should I read it out?

OK. As for shifting from animal models preclinically to chip modelling, so that's the organ on a chip for early safety research, we still don't have rat or mouse ovarian histology for HPV vaccination or indeed for COVID vaccine, it's not available. How could this inform modelling?

That’s a great question.

The question to translate for those of you who don't speak science, basic science, is some of those new technologies that I showed you, not all cells are available.

They think like said, a stem cell's a stem cell or a cell's a cell or it doesn't really matter. The companies that produce a lot of the cells that they sell to researchers, sex cells. No, that sounds awful. The company, they don't always offer a variety of cells and here I'm just going to say again, yes, it's sex, but it's also geographic ancestry. Depending on where your ancestors came from, there's different genomic or genetic distributions and so this idea of diversity, are the cells really available to do all this? And the answer's no. And this person's asking, what do we do about this? Well, I think you challenged the company companies, and I think you say, actually, I want this other cell, where can I get it?

Or believe it or not, there's a there's a group in South Korea who now has a website listing all the different cells that are available from different countries that may help with this.

But how can we inform modelling? I think we need to correct the basics. It's like the artificial intelligence, if you don't use the right or it's like baking, maybe. I don't know if you don't have the right ingredients or the flour. I live in Canada and US flour is different and all the recipes just don't work if you use Canadian or US flour. I don't know if you know that, but so it's sort of the same thing, right? You need the proper ingredients in order to get the results that you want. I don't have a quick answer for you, but you're thinking about it and that's important. As long as you're asking questions that will change the culture.

50:56 Prue Torrance
I have one last question for you.

If there are none other online, how have you dealt with resistance when you come across it to people not wanting to apply new methodologies and wanting to do the same as they've always done?

51:11 Dr Cara Tannenbaum
That's a great question. I mean, I'm answering to this audience that folk for whom the system has worked historically, of course they don't want to change, we'll leave it at that.

But that time has passed. We're not forcing anyone to apply to NHMRC, are we? Do people have to apply? I think if you're applying for funding or if you're delivering care, you want to be doing internationally recognised, cutting-edge science that's rigorous, high quality, relevant, applicable, reproducible. If that that bothers you because you didn't do that in the past, then we have, I don't know what your funding rate is here, but in Canada we have a lot of amazing scientists. We have a very low funding rate. I'm very happy to fund the folks who are going to do it with integrity.

I could also tell you that in Canada, the US and the European Commission, we did not increase our budget. There might have been a little bit of reorganising and who got funded and how much they were asking for.

How could you be running a clinical trial these days without being able to disaggregate with efficient power, safety and efficacy of medications for the folks who the diverse folks who are going to be using them at the correct dose.

I always say try me, submit what you think is right and let the peer reviewers and evaluators decide if you're going to get funded. I'm not telling you have to. If you don't want to do it, don't do it. But you may not win a Nobel Prize or get published.

I think it was one more question possibly.

My group implemented a survey about COVID vaccination completion in young people during the pandemic and included gender identity. Even though it seemed that gender diversity has nothing to do with vaccination, we found this subgroup had higher levels of psychosocial distress than other groups. We did not have any complaints about asking about gender.

Well, thank you for sharing that. I think you'll find that people will appreciate it and that we will, it's kind of kind of interesting. We always talk about in science the normal curve and two standard deviations and always looking for the average. Well, maybe equity science and anyone who has an equity strategy needs to take those outliers. But we haven't measured and have the worst outcomes because of stigma and because we haven't included them and re-centre them in terms of shifting resources to, I think you call it closing the gap here for different populations that really haven't benefited from our science.

Kudos to you and there's a few more questions, but I don't know if we're out of time.

Can I take one or two more? OK.

Do you know if female researchers are more likely to conduct more equitable research or to focus on research on female topics?

Yes, I do know. There have been some great articles published like even in The Lancet about folks, if you include people with lived experience on the team, they are more likely to think of things that people with lived experience do not think about.

We even know that ER docs, if they have, you know, a uterus, then they will be more likely to think it's, I don't know, endometriosis or something like that. If a woman comes in with pain, then if they don't.

There is good evidence and some pretty rigorous studies showing this. That's a yes on your question. They've even done first and last authors sex or gender of the authors.

Then another question is I'm interested to know if you have any tips, please for adapting standardised questionnaires or validated measures.

My answer is yes, please do it. So many have been, there are a number. I'm not sure what you're trying to adapt.

Clearly it would be good to look for measures that already exist. In Canada, we do have a number of measures and because this research has been done in other countries, you should first do a literature review to find out if the construct that you wish to measure, there's already been a questionnaire design for it.

In terms of validating them, I would direct you to some research by Londa Schiebinger, who just came out with a validated genders questionnaire and the research methods for how to adapt it and how to develop it or in that paper, because I'm not sure I want to go in as a reviewer.

Maybe ask questions. Thank you. OK. You like my answer good. All right, We're good.

56:14 Prue Torrance
OK, Thank you very much. Thank you for everyone joining us online for the Speaking of Science series. Please join future ones.

In December, we have one in the week celebrating International Day of Disabilities, so join us for that.

A reminder that this is recorded. Please share this one with all of your colleagues who didn't come today. Think there's lots to learn from Cara's presentation.

Please join me in thanking Dr Cara Tannenbaum for giving us her generous time and insights today.
Thank you.

End of transcript.