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Engendering equality in research

March 13, 2020

Women are underrepresented in research; meet 3 ASU researchers who are actively working to change that

Her breathing is shallow and sporadic, her stomach is doing somersaults and her jaw is locked. She is having a heart attack.

But according to medical standards, she isn’t.

The doctor says because there is no chest pain or pressure, the patient is not presenting typical symptoms for a heart attack. She is sent home with a less life-threatening diagnosis.

The doctor was right about one thing: The patient wasn’t typical. She was a woman.

Despite making up half the population, women aren’t considered “typical” subjects in many facets of research. Many products and services simply aren’t tested on women. Women are left out of medical research and genetic studies. And women are underrepresented among the people conducting research, as well.

As we celebrate Women’s History Month this March, researchers across Arizona State University talk about how the systems in and around scientific research facilitate the underrepresentation of women — and how they are working to change things.

XX marks the spot

In 2013, less than a third of studies analyzing the genome included the X chromosome, one of the two sex chromosomes. Despite policies encouraging researchers to include sex as a biological variable, these numbers have not increased in the past seven years, according to data from the National Institutes of Health.

The reasons behind these stagnant statistics are technical, historical and personal, according to Melissa Wilson, an assistant professor in ASU’s School of Life Sciences.

“In computational sciences, we view ourselves as being quantitative and therefore above petty distinctions. But the whole history of biomedical research suggests that we haven’t been,” Wilson said.

Her lab investigates sex chromosome evolution, sex-biased research and comparative genomics. By incorporating the X and Y chromosomes in studies, the lab explores sex differences in health and disease.

Melissa Wilson

Melissa Wilson, an assistant professor in the School for Life Sciences, investigates sex chromosome evolution, sex-biased research and comparative genomics. Photo by Andy DeLisle

Over the past 150 million years, the X and Y chromosomes have evolved to be very different. The Y chromosome has lost 90% of the gene content it once shared with the X chromosome.

Many of the genes found on sex chromosomes interact with genes found throughout the genome. In spite of this, most studies of human and animal genomes exclude the X and Y chromosomes because they don’t follow the typical chromosome pattern.

“Ninety-five percent of the picture is not the whole picture,” Wilson said. “You can’t partition the X chromosome off into its own space, because it’s still interacting with other genes.”

Some researchers and scientists hesitate to include sex as a variable in research because pregnancy and the menstrual cycle contribute to variability. However, sex is the most prevalent variable in the human population.

“It seems really unfortunate that we are going to exclude half of the population. Even if you are understanding the research in one sex, you not understanding it in everyone,” Wilson said.

Diseases don’t strike men and women equally. Wilson’s lab recently published a paper looking at sex differences in liver cancer, which impacts men four times more than women.

“If you’re only studying males you are not able to figure out what it is about females that allows them to have lower incidences of liver cancer,” Wilson said. “We can look at what is wrong, but also things that are potentially protective in each sex.”

graphic of human chromosome pairs with sex chromosomes highlighted

Each human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes. Twenty-two pairs of the chromosomes (in white) are the same in both male and females. The 23rd pair are the sex chromosomes, and can differ between the sexes. Females have two copies of the X chromosome, while males have one X and one Y chromosome. Some individuals do not follow these sex chromosome patterns, as a result of genetic alterations. Illustration by Charity Chong.

Many labs do not include sex differences in their research questions because they don’t have the infrastructure to do so. To combat this problem, Wilson is developing new methodologies to make it easier for people to incorporate sex chromosomes into their analyses.

“If it’s a struggle for people to include it, then they won’t,” she said. “But it really only takes one second to ask, ‘Does this sample have a Y chromosome or not?’ It is simply constructing a slightly different model with a bit of thought.”

Although Wilson encourages scientists to consider sex in their research, she also warns against reducing sex to a singular variable. Because sex is not a binary, it becomes problematic when used incorrectly.

“With all of the factors involved in sex, we move into a very high-dimensional space,” she said. “It won’t be enough to add male and female as categorical variables to your study. It can be a start, but it won’t be enough.”

Wilson also acknowledges the risk that focusing on sex differences will reinforce gender stereotypes and discrimination. She reminds scientists that the variability across humans does not translate to inferiority and superiority.

“It’s not a slippery slope unless you make it one,” she said. “To say something is different, does not mean to say that something is better or worse. We just want to know if these differences translate to disease risk and treatment variability. Socially you can acknowledge variation without having to take that extra step.”

Wilson affirms that the templates and methods for including sex as a variable in research will get stronger and more available in the future. Researchers who are not doing this type of analysis will not be excluding sex because they don’t know how to, but rather because they are actively choosing not to.

“People will have everything they need. They still may not have the will,” she said.

Growing a stronger STEM

The will to include sex differences in studies will likely increase as the number of women researchers increases. Unfortunately, society loses women at every step along the path of STEM careers.

Throughout elementary, middle and high school, girls actively participate in high-level math and science courses, displaying achievement on par with their male classmates. However, the vast majority of undergraduate degrees in engineering, computer science, physics and mathematics are earned by men.

Although women earn a growing number of science and engineering doctoral degrees, they still hold less than one-third of doctorates in math, statistics, computer sciences and engineering. In the workforce, women receive only a third of NIH research grants across industry and academia. Women also hold less than one-third of leadership positions in all academic STEM fields.

For Kiki Jenkins, attributing these statistics to women “falling through the cracks” is too passive in explaining the problems of the STEM research pipeline.

The pipeline is not just leaky — it is fundamentally broken. 

“This problem is systemic and it comes from all places,” said Jenkins, an associate professor in the School for the Future of Innovation in Society. “It’s not that there are holes that women fall through; there are barriers and obstacles that are thrown in our faces. If we try to dodge them, they chase us down and run us over.”

photo of Jenkins with mentee in her office

Lekelia (Kiki) Jenkins, an associate professor in the School for the Future of Innovation in Society, talks with her mentee, Gabby Lout, in her office. Photo by Andy DeLisle

The system that female researchers operate in is aggressively hostile to women, she said. Jenkins says her mother was told as a child, “Math isn’t for girls.” When her mother pursued a professional degree, she had a fear of math because of what she had been told over and over again.

“She excelled regardless,” Jenkins said. “But if we have a system telling young girls they aren’t capable of something, that’s hard to overcome.”

Women don’t just have to be good scientists to succeed in this system; they have to be “social linebackers and strategic minds,” according to Jenkins. “Those things are not relevant to how good of a scientist they are, but they need them to succeed in this system.”

Jenkins’ personal experiences have fueled her passion for being an advocate for young girls and people of color in science. At middle school science fairs, Jenkins would see girls and kids of color who were smart and had great ideas but didn’t know how to navigate spaces that were unfamiliar and unwelcoming to them.

“Because they didn’t know how to work the system, their brilliance got lost, and as a result that benefit to society got lost,” Jenkins said. “That’s just not fair and that’s not good for everyone.”

Alongside 124 other women, Jenkins serves as an IF/THEN Ambassador for the American Association for the Advancement of Science (AAAS). In this position, Jenkins empowers and inspires the next generation of female scientists through media programming and community advocacy projects.

“What AAAS is doing is giving us a larger platform to amplify what we’re already doing,” Jenkins said. “It is really amazing the amount of money, effort and grand thinking that AAAS is putting behind these initiatives.”

Jenkins encourages everyone, inside and outside of STEM fields, to act as allies to women in STEM.

“Stand up and leverage your power,” she urged. “Chances are you’re in a position to stand up and do things that a woman you’re allied with cannot. The system will not change until we use this untapped power.”

Instead of asking surface level questions like “How many women work here?” society can ask deeper questions like “How quickly are women being advanced?” and “Is there equality in resources and opportunities?” These questions can uncover more subtle forms of discrimination.

“It’s not that there are holes that women fall through; there are barriers and obstacles that are thrown in our faces. If we try to dodge them, they chase us down and run us over.” 

— Kiki Jenkins, associate professor in the School for the Future of Innovation in Society

For girls and women pursuing STEM degrees and careers, Jenkins encourages personal community building and thorough research about academic programs.

“One thing women can do to address these problems is build a strong support community,” she said. “Also talk to people in your program and people who have matriculated out of the system. Get the truthful insights about diversity and inclusion at an institution before you decide to grow your roots there.”

Designing (for) women

Medical research is not the only area where women are excluded from studies. The lack of women as participants in product testing and sex-biased thought in design has led to a world that’s ill-fitted for women — from extra-large smartphones in undersized pants pockets to chilly office temperatures. Even life-saving devices, like seatbelts and airbags, were initially designed without women in mind.

Erin Chiou, an assistant professor of human systems engineering at the Polytechnic School, is one of the experts asking why these systems were not designed with everyone in mind.

Chiou is an editor of a recently released book, “Advancing Diversity, Inclusion, and Social Justice Through Human Systems Engineering.” It discusses incorporating marginalized groups into population samples, designing for marginalized groups specifically, and the push for more women and minorities in STEM education.

Erin Chiou

Erin Chiou, an assistant professor of human systems engineering at the Polytechnic School, is an editor of a recently released book, “Advancing Diversity, Inclusion, and Social Justice Through Human Systems Engineering.

The book details the historical and systematic omission of certain demographics in development phases. Ultimately, this results in one compromised design for a wide variety of users.

Designing for sameness intensifies disparities that already exist in society. For example, barrier curbs along roads make it difficult for people who use wheelchairs to access places that the “average human” can.

In contrast, universal design considers all people — regardless of age, race, gender and ability — when designing buildings, products or environments.

“Curb cuts on sidewalks are meant for people in wheelchairs to be able to navigate safely and comfortably on sidewalks as pedestrians already do,” Chiou said. “This design also benefits older adults and parents with strollers.”

Designing with women in mind isn’t just the ethical thing to do. It also translates to more money for businesses. Women currently drive 70%-80% of consumer spending worldwide, according to Bloomberg.

Chapters in Chiou’s book examine how women-centered design is reaping significant economic and social benefits for system developers, investors and customers.

“I think the most important thing we can contribute as a field is to let other engineers know that designing for the average human is actually excluding a large majority of the population,” Chiou said. “Who exactly is an average human?”

Light at the end of the pipeline

Wilson, Jenkins and Chiou are part of a growing movement to make research more inclusive. At the federal level, the Office of Women’s Health Research at the National Institutes of Health brings together people in the scientific community to think about why and how sex should be included as a biological variable. Wilson, who is a member of the Women’s Health Research committee, is currently collaborating with other members on a paper about best practices in genetic research.

Change is happening on an institutional level, as well. In ASU’s new computational life sciences certificate program, for example, students must enroll in an ethics course to address problems like sex bias in genomics research.

“We are really proud that our students have discussed the responsible conduct of research and bioethics,” said Wilson. “I’m hoping this gives future scientists a framework to interpret their results and what kinds of questions to ask in the first place.”

“People will have everything they need. They still may not have the will.” 

— Melissa Wilson, assistant professor in the School of Life Sciences

In the marketplace, applying the values of universal design translates to an inclusive environment and better products that will appeal to more people.

“Including a diverse population in your research, or targeting a diverse population in your design, will actually have a greater impact on our world than designing for the average,” Chiou said.

Jenkins says she is seeing increased diversity in the STEM community.

“For the longest time, I was the only black woman in a room,” she said. “That’s changing. I see young black women as graduate students or postdocs more frequently.”

But, she adds, there is much more work to be done.

“Yes, there is change. No, it is not as fast as I’d like it. In positions of power and leadership things are not changing. Those people are largely male and largely white.”

Through her work as an AAAS IF/THEN Ambassador and community advocate at ASU, she is working with the next generation of scientists to change that, alongside colleagues across the university such as Wilson and Chiou.

“This is not a side-job, an extra, an add-on or outreach,” Jenkins said. “This is imperative, so we should value it more.”

Written by Maya Shrikant. Banner illustration by Patrick Cheung.

 
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High-tech implant could ease harmful effects of brain ailment

March 13, 2020

Hydrocephalus is among the neurological disorders for which modern medical science remains stymied in the search for a cure. Even treatment for what is commonly called “water on the brain” is looked upon as antiquated in an age of expanding technological innovation.

Characterized by an abnormal buildup of cerebrospinal fluid in the brain, untreated hydrocephalus can trigger swelling, headaches and convulsions, impair cognitive functions and walking and even cause death.

The condition affects people of all ages, including infants — an average of one of every 500 newborns in the United States alone — as well as older children and adults, who can develop hydrocephalus from many conditions. It also affects people with post-traumatic stress disorder, or PTSD, many of whom are current or retired members of the military.

The current treatment process, called shunting, involves diverting the excess fluid from the brain using catheters. The tubing is routed from inside the skull and then underneath the skin to another cavity in the body, such as the abdominal cavity or the heart, where it is absorbed back into the body.

Shunting, however, has a failure rate of about 40% within two years after the procedure is performed and more than 95% within a decade.

But hope for a considerably less invasive and more resilient treatment may lie in advances in one especially fast-growing sphere of technology: micro-electro-mechanical systems, called MEMS.

These miniaturized electrical and mechanical devices are used mostly in semiconductor manufacturing, cell phones, digital displays, wireless communications, aerospace and automotive technologies, but their capabilities are being more fully explored beyond those applications.

Junseok Chae, a professor of electrical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, has been honing his expertise in the use of MEMS technology to develop medical devices.

man talking in lab

In his research laboratory at Arizona State University’s Tempe campus, Professor Junseok Chae talks about progress he has been making through a collaboration with neurosurgical experts at the Barrow Neurological Institute to develop a more effective and less invasive treatment for hydrocephalus. Photo by Connor McKee/ASU









Progress on that endeavor recently helped earn two grants totaling $2 million from the U.S. Army’s Congressionally Directed Medical Research Programs. The funding supports an ongoing collaboration to develop brain implants that treat hydrocephalus. The work involves Chae and neurosurgical experts at Barrow Neurological Institute in Phoenix, one of the premier neurosurgery centers in the United States, and at Phoenix Children’s Hospital.

The partnership began in 2006, when Dr. Ruth Bristol, a pediatric neurosurgeon at Phoenix Children’s Hospital who has been treating patients with hydrocephalus for almost 20 years, asked Chae to work on a more effective treatment. That request has led to more than 12 years of multidisciplinary collaboration that also involves Dr. Mark Preul, a neurosurgeon and director of neurosurgery research at the Barrow Neurological Institute. Bristol is also with the institute.

Preul’s expertise includes the development and testing of advanced technologies for neurosurgery. One of the Army medical research program’s grants went to ASU to support Chae’s efforts. The other grant went to the Barrow Neurological Institute to fund work led by Preul at Barrow’s neurosurgery laboratory.

“We want to implant a device manufactured from MEMS technology that will drain the cerebral spinal fluid just like the way the body does it naturally when there is no hydrocephalus,” said Chae, who teaches in the School of Electrical, Computer and Energy Engineering, one of the six Fulton Schools.

Cerebrospinal fluid, which is a watery fluid produced by special cells in the brain, surrounds and bathes the brain and the spinal cord. Almost a pint of it is produced every day in the brain’s cavities, called ventricles.

The fluid flows around the brain and spinal cord through the spaces between the brain’s membranes before it is absorbed into the bloodstream. Along the way, cerebrospinal fluid performs critical functions such as protecting the brain by acting as a shock absorber, bringing nutrients to the brain and taking waste out.

In a healthy brain, Chae explained, the fluid circulates through the brain and then flows through tissue structures called arachnoid granulations — projections of the arachnoid membrane — which rest on one of the brain’s meningeal layers that support the framework for cerebral and cranial blood vessels.

“What we want to do is implant our MEMS device onto the meningeal layer to act like natural arachnoid granulation,” Chae said.

The arachnoid granulations regulate the flow of cerebrospinal fluid from the subarachnoid space to the sinus space where it is absorbed back into the body’s blood stream.

In cases of hydrocephalus, the flow, drainage and absorption process gets blocked, causing the troublesome cerebrospinal fluid buildup in the brain.

Chae’s team describes its brain implant as an artificial arachnoid granulation that will “emulate the body’s arachnoid granulation valve system and restore brain fluid flow to its natural pathway by mimicking the body’s natural process,” he said.

To do this, the researchers are using MEMS technology to manufacture the tiny device that regulates the fluid flow through the properties of a hydrogel made of a biocompatible polymer, which has a unique swelling feature enabling it to regulate the flow of cerebrospinal fluid between the subarachnoid and sinus spaces.

man holding chip

Electrical engineering doctoral student Seunghyun Lee examines one of the small implantable devices designed to help prevent the debilitating effects of hydrocephalus. Photo by Connor McKee/ASU


“This will be a hydrocephalus treatment that is a minimally invasive procedure compared to the current bulky shunt treatment system. It won’t require any catheters, which are currently the biggest cause of the failure of the shunt system,” Chae said.

The new treatment “will have no implanted batteries or electronics but will operate with a fully passive artificial valve to mimic the body’s natural regulation of brain fluid,” Chae said. “The fluid will flow into an outer layer of the brain (the superior sagittal sinus), where it can be reabsorbed into the blood stream.”

Chae, Bristol and Preul are among the co-authors of three articles published in research journals that report on recent technical advances related to the new treatment — in IEEE Transactions on Biomedical Engineering; the  Annals of Biomedical Engineering, part of the Springer Nature Journal, and in the current edition of the American Chemical Society’s ACS Sensors journal.

Despite the promise of the new treatment, Chae cautions against expectations for it to be put into practice in the near future.

“Good things are happening in our research, but this is still a long-term exploratory project,” he said. “We have to go through the Food and Drug Administration’s process and many other validations before we are certain we can could deploy this treatment in a completely safe manner.”

Success in the endeavor, however, would “translate into dramatically improved quality of life for hydrocephalus patients,” Chae said.

Chae credits some of the progress on the project to his student lab assistants.

Electrical engineering doctoral student Seunghyun Lee has contributed to development of a MEMS device, including testing it in the lab, collecting testing data and analyzing the data using advanced statistical methods.

Daniel Beltran, an electrical engineering undergraduate student, has been helping to manufacture the MEMS device, as well as develop the lab setup to test multiple devices simultaneously. 

Top photo: Researchers are using advanced micro-electro-mechanical systems, or MEMS, technology to manufacture small implants that will restore the normal flow of cerebrospinal fluid through the brain to relieve pressure resulting from hydrocephalus. Photo by Connor McKee/ASU

Joe Kullman

Science writer , Ira A. Fulton Schools of Engineering

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