The quest to show that biological sex matters in the immune system
She ultimately found a postdoctoral position in the lab of one of her thesis committee members. And in the years since, as she has established a lab of her own at the university’s Bloomberg School of Public Health, she has painstakingly made the case that sex—defined by biological attributes such as our sex chromosomes, sex hormones, and reproductive tissues—really does influence immune responses.
Through research in animal models and humans, Klein and others have shown how and why male and female immune systems respond differently to the flu virus, HIV, and certain cancer therapies, and why most women receive greater protection from vaccines but are also more likely to get severe asthma and autoimmune disorders (something that had been known but not attributed specifically to immune differences). “Work from her laboratory has been instrumental in advancing our understanding of vaccine responses and immune function on males and females,” says immunologist Dawn Newcomb of the Vanderbilt University Medical Center in Nashville, Tennessee. (When referring to people in this article, “male” is used as a shorthand for people with XY chromosomes, a penis, and testicles, and who go through a testosterone-dominated puberty, and “female” is used as a shorthand for people with XX chromosomes and a vulva, and who go through an estrogen-dominated puberty.)
Through her research, as well as the unglamorous labor of arranging symposia and meetings, Klein has helped spearhead a shift in immunology, a field that long thought sex differences didn’t matter. Historically, most trials enrolled only males, resulting in uncounted—and likely uncountable—consequences for public health and medicine. The practice has, for example, caused women to be denied a potentially lifesaving HIV therapy and left them likely to endure worse side effects from drugs and vaccines when given the same dose as men.
Men and women don’t experience infectious or autoimmune diseases in the same way. Women are nine times more likely to get lupus than men, and they have been hospitalized at higher rates for some flu strains. Meanwhile, men are significantly more likely to get tuberculosis and to die of covid-19 than women.
In the 1990s, scientists often attributed such differences to gender rather than sex—to norms, roles, relationships, behaviors, and other sociocultural factors as opposed to biological differences in the immune system.
For example, even though three times as many women have multiple sclerosis as men, immunologists in the 1990s ignored the idea that this difference could have a biological basis, says Rhonda Voskuhl, a neuroimmunologist at the University of California, Los Angeles. “People would say, ‘Oh, the women just complain more—they’re kind of hysterical,’” Voskuhl says. “You had to convince people that it wasn’t just all subjective or environmental, that it was basic biology. So it was an uphill battle.”
Despite a historical practice of “bikini medicine”—the notion that there are no major differences between the sexes outside the parts that fit under a bikini—we now know that whether you’re looking at your metabolism, heart, or immune system, both biological sex differences and sociocultural gender differences exist. And they both play a role in susceptibility to diseases. For instance, men’s greater propensity to tuberculosis—they are almost twice as likely to get it as women—may be attributed partly to differences in their immune responses and partly to the fact that men are more likely to smoke and to work in mining or construction jobs that expose them to toxic substances, which can impair the lungs’ immune defenses.
How to tease apart the effects of sex and gender? That’s where animal models come in. “Gender is a social construct that we associate with humans, so animals do not have a gender,” says Chyren Hunter, associate director for basic and translational research at the US National Institutes of Health Office of Research on Women’s Health. Seeing the same effect in both animal models and humans is a good starting point for finding out whether an immune response is modulated by sex.
Chinese creators use Midjourney’s AI to generate retro urban “photography”
If you saw these images pop up on your timeline, would you be able to tell if they were real photographs of the southwestern city of Chongqing in the 1990s?
In fact, none of them are real. Zhang Haijun, a street photographer in Chongqing, generated these images with Midjourney, an image-making artificial-intelligence program.
A number of artists and creators are generating nostalgic photographs of China with the help of AI. Even though these images still get some details wrong, like the number of fingers that humans have or what Chinese characters look like, they are realistic enough to trick and impress many social media followers, including me.
Retro AI artwork like Zhang’s has also caught the attention of Tong Bingxue, a collector of Chinese historical photographs. He reposted some of them to his popular Twitter account China in Pictures last week.
These generated photos are indeed aesthetically pleasing, Tong says. They look sophisticated in terms of standard photography metrics, like definition, sharpness, saturation, and color tone. “When people look at things on social media, these [attributes] are the first things that catch the eye. The authenticity of the photo comes second,” he says. Real historical photos, on the other hand, sometimes look amateur or come with material imperfections.
Zhang, the creator of the AI images above, was born in Chongqing in 1992. He grew up near the Chongqing Iron and Steel Company, one of the oldest and largest steel factories in China, and remembers watching the workers when he was about seven years old. “When I was little, I would often watch them come out of the factory during their break, sit on the ground, smoke a cigarette, and look into the distance. There were stories in their eyes,” he says.
When he turned that experience into an image-generating prompt for Midjourney, he was amazed by the results. “What the AI generated—the look of resilience in their eyes and the way they are dressed—it looks exactly the same as what I described to it,” he says.
Now, Zhang pays more than $200 a year for Midjourney, and uses it to generate new retro photographs with different themes: rural weddings in the ’90s, physical laborers for hire waiting in the market, and Chongqing street fashion. Each time, he writes the prompts in Chinese, uses machine translation tools to convert them to English, feeds them into Midjourney, and spends about 20 minutes tweaking them to get the ideal result.
Technology and industry convergence: A historic opportunity
And it’s that combination of technology and human ingenuity, as we say, and as Danielle just alluded to in her medical example on cancer treatment, that is really where the greatest value and the greatest impact is going to come. We believe the companies which are going to be leaders in the next decade are going to need to harness five forces, and all of these forces are going to require technology and ingenuity to come together. They’re going to require organizations to work across all elements of their organization, to work with new partners, to expand into new areas and ecosystems, to learn and collaborate with innovators across industry, as well as across industry and academia and beyond to really push the boundaries of science and impact.
The five forces that we see right now, the trends that we’re seeing that are impacting our clients the most really start with what we believe underpins everything right now, and that is something we’re calling total enterprise reinvention. And we really started to see this come to the fore as we moved through covid. And what we’re seeing now is that as companies are looking to enter these new waves of change and opportunity, that they’re needing to execute strategies to change and transform all parts of their business through technology, data, and AI, as Daniela just talked about, to enable new ways of growth, new ways of engaging customers, new business models, new opportunities, but they’re doing it in a very different way. They’re doing it in a way where they’re looking at every part of their organization and the technology and digital core that underpins it at the same time, so we believe we’re in the early stages of this profound change, but we believe it’s going to be the biggest change since the industrial revolution.
And embracing total enterprise reinvention often requires something that we call compressed transformation, which are bold transformational programs that, as I said, span the entire organization with different groups working together in ways that they never did before in parallel, but in very accelerated timeframes. And underpinning all this is leading edge technology, data, and AI. At the same time, the second trend we’re seeing with our clients, and we certainly are all reading about it and of hearing about it for the past few years, is the power of talent and the importance of the human side of this equation. And we think that one of the forces that’s going to shape the next decade with talent at front and center is not just the ability to access talent, but really for organizations to learn to be creators of talent, not just consumers. To unlock the potential of the humans in their workforce. And that’s going to require technology to unlock that potential. And again, as Daniela just gave in some of her examples, to compliment the talent that they have in the organization.
The third is sustainability. That trend is … I would say personally, I’m very pleased to see this trend underpinning everything that we’re doing and everything that our clients are thinking about right now. We believe that every business needs to be a sustainable business. And every industry is looking at this in a way that is unique to their industries. But whether it’s consumers, employees, business partners, regulators, or investors, we know that we’re moving in a direction where companies are being required to act. To make a change, not just around climate and energy, but areas like food insecurity and equality. All of those issues are coming to the fore, and underpinning this, again, is the ability to leverage new bleeding technologies to accelerate the pace of change and find solutions to the issues that we’re facing as a planet and across society.
The fourth force that we’re seeing is the metaverse. Now, there’s been a lot of confusion, and a lot of talk about the metaverse, but our view is that the metaverse is a continuum, and we’re seeing this come to the fore in the marketplace right now. As we look at the metaverse and how that’s going to impact, just if you think all the way back to when the internet was in its early stages, we believe that the impact is going to be that great. And while it’s early stages and not everybody can see exactly how the impact is going to be there, we believe that this is going to impact not just consumers, and of course interesting areas like virtual reality and using AI to bring new experiences to life, but also to look at extended reality, to look at digital twins, smart objects. So how do cars and factories run? What’s happening with edge computing? Looking at blockchain and new ways of payment. All of those things are going to change the way businesses operate and really the way society operates, and we believe that this is going to underpin change as we move forward over the next five to 10 years.
And then lastly, the fifth force is what we’re calling ongoing tech revolution. And the ongoing tech revolution is a pretty broad expansive category, often pushed by our friends in the academia world around science, but we believe in the coming decade, the pace of technological innovation is not just going to continue but accelerate, which we believe is going to create positive change. New technology, whether it’s in quantum computing or it’s in areas, as I said, like blockchain or material science or biology, or even space, we believe this is going to open brand new areas of opportunity. And all of these things are allowing companies, our clients to find new ways to not just serve their customers, but to monetize their investments, to impact society, to impact their employees, and to drive positive change for their business as well as for the world around them.
Laurel: Yeah. Kathleen, I feel like some of that acceleration happened in these last few pandemic years so that businesses and consumers are operating differently from remote healthcare solutions to digital payments, greater expectations of those immersive virtual experiences. But how can organizations and technologists alike then continue to innovate to anticipate the future, or as Accenture likes to say, learn from the future? You have some good examples there, but the five different areas all kind of also lead to this acceptance of change.
Kathleen: Yeah, they do. And they also lead to embedding data in everything, in new ways into every change that organizations are putting forward. When we think of learning through the future, we think about organizations and leaders who are constantly seeking new data and insights, not just from inside their organization, but from outside their organizations’ four walls. So we like to use the phrase intentional futurists. These are people and leaders and organizations who use AI-based analysis to find patterns, anticipate trends, detect new sources of growth opportunities, understand their consumers, their customers, other enterprises, the markets and their employees better.
Delivering insights at scale by modernizing data
This data is often siloed in enterprise resource planning (ERP) systems. However, with ERP data modernization, businesses can integrate data from multiple sources, which will ensure data accessibility and create the framework for digital transformation. Migrating legacy databases to the cloud also gives companies access to AI and ML capabilities that can reinvent their organization. According to Anil Nagaraj, principal in Analytic Insights, Cloud & Digital at PwC, companies that modernize their ERP data see increased efficiencies, costs savings, and greater customer engagement, especially when it’s built on a cloud platform like Microsoft Azure.
Cloud transformation—along with ERP data modernization—democratizes data, empowering employees to make decisions that directly impact their segment of business. And in an increasingly competitive marketplace, becoming data-driven means organizations can make faster, timelier, and smarter decisions.
This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff.