Aquaculture experts at the Roslin Institute have collaborated with industry partner Atlantic Aqua Farms to map the complete set of chromosomes for the blue mussel, an important commercial species in Europe and North America.

Researchers aim to support mussel farming and improve disease resistance using advanced gene sequencing technologies.

The high-quality genome map identifies over 65,000 genes, providing a comprehensive blueprint of the mussel’s genetic makeup.

This development is particularly important for the aquaculture industry, which relies on efficient and sustainable breeding practices to meet the growing demand for mussels.

Aquaculture Breeding

In Prince Edward Island, Canada, where the world’s only commercial mussel hatchery exists, this information will allow farmers to select mussels with desirable traits.

For instance, the new data will enable farmers to breed mussels with stronger byssus threads, which are crucial for the mussels to attach securely to ropes, ensuring a more stable yield.

Additionally, the genomic insights will help in selecting mussels that grow faster and produce more meat, enhancing overall productivity for mussel farms.

Disease Resistance

The mapped genome allows scientists to study the immune responses of different mussel populations, enabling researchers to identify how certain populations are better able to withstand threats posed by climate change and emerging diseases. This can lead to targeted breeding programmes that enhance disease resistance.

This will help reduce losses due to illness and improve the health and sustainability of mussel populations, the research team says.

Ecosystem conservation

This research not only benefits commercial aquaculture, but also contributes to the conservation of wild mussel populations by ensuring their health and genetic diversity, researchers explain.

Blue mussels can spread and establish themselves in non-native regions, affecting local ecosystems. Accessing detailed genomic data will enable scientists to track and mitigate the impact of these invasive populations, preserving the balance of marine environments.

In the coming months, the research team plans to explore the genetic diversity of blue mussels in Scotland, leveraging the complete genome map for more detailed analyses.

This research was published in the G3 Genes, Genomes, Genetics journal. The project was funded by Genome Canada and carried out in close collaboration with Atlantic Aqua Farms.

“This research project marks a significant advancement in aquaculture. It showcases how genomic research can provide practical solutions for commercial aquaculture and environmental conservation,” says Dr. Tim Regan, Career Track Fellow, Roslin Institute.

While Riddhiman Garge, first author of a study published in the March 2024 issue of G3: Genes|Genomes|Genetics, was earning his PhD at the University of Texas, he met brewer Chip McElroy. McElroy, who owns Live Oak Brewing Company and has a Ph.D. in biochemistry, was curious about what happens to brewing yeast inside fermentation tanks. The pair teamed up with Garge’s colleagues to investigate some aspects of this question.

The importance of brewing yeast

In addition to being a classic research organism for genetics and molecular biology, Saccharomyces cerevisiae, sometimes called brewer’s yeast, has a host of commercial uses and is especially important in beverage fermentation—the global beer market is now worth more than $750 billion.

Despite its economic impact, however, brewer’s yeast has been understudied in its beer-making context. The G3 study investigates one aspect of commercial fermentation: how ale yeast proteins change throughout successive fermentations.

The impact of serial repitching on the yeast proteome

During brewing and fermentation, yeast must adapt to increasingly harsh conditions, including fluctuating nutrient, ethanol, and oxygen levels. (Indeed, too much alcohol stresses both yeast and humans!) The commercial practice of serial repitching may also impact the yeast proteome.

In serial repitching, brewers harvest yeast cells at the end of a fermentation cycle and use them to inoculate (or pitch) a new batch of beer. Commercial brewers repitch eight to ten times, stopping as the flavor, aroma, and yeast viability deteriorate over time.

To better understand molecular changes associated with serial repitching, researchers sampled populations of Weihenstephan Wheat yeast directly from the fermentation tank. They applied shotgun mass spectrometry to measure proteomic changes throughout two fermentation cycles separated by fourteen rounds of serial repitching. The time course began with Batch 1—the freshly prepared yeast stock—and ended after fourteen repitches (Batch 15), and sampling was performed at comparable time points across the four days of brewing.

Results

Garge et al. report that protein abundance at the earliest fermentation timepoints was the most different compared to the rest of the timepoints. Batch 15 had elevated synthesis enzymes for ergosterol, which helps mitigate the stress of low-oxygen environments; however, batch 15 had fewer isobutyraldehyde synthesis enzymes. Isobutyraldehyde is linked to a grainy flavor profile that is considered desirable for some beers but an off-flavor in others. This dataset offers a starting point for tweaking flavor and strain characteristics in commercial and craft breweries.

The authors also set up an interactive web interface cataloging the fermentation-based protein changes they observed to aid hobbyists, scientists, and brewers. 

Next steps

Further analysis of the study data and future studies of proteins and metabolite changes across fermentation and repitching will help brewers engineer yeast strains, optimize brewing workflows, and study trends that undergird domestication processes. In addition, such real-world research can help make inferences about known and unknown biology. For instance, the function of many S. cerevisiae genes is unknown. “By looking at [these genes] in new contexts, maybe we can infer function,” Garge says. “People think that if you have a biology degree, you can only study things in the lab. But this study [demonstrates] that there are interesting biological processes going on in the everyday world,” Garge says.

Advances in genome engineering are of broad interest (e.g., 2020 Nobel Prize in Chemistry); however, since they occur at a rapid pace, it’s difficult for scientists to stay up to date. Attending conferences is crucial for learning about cutting-edge advances, but accessibility barriers such as travel and registration costs exist. Additionally, while principal investigators are typically invited to give talks, the first author scientists who carry out the research are better suited to answer technical questions and would greatly benefit from presenting their work.

On November 30, 2023, Harvard Medical School hosted a hybrid symposium on recent advances in genome engineering, organized by three postdoctoral researchers: Justin Bosch, University of Utah; Joana Ferreira Da Silva, Massachusetts General Hospital and Harvard Medical School; and Raghuvir Viswanatha, Harvard Medical School. Sponsored by a GSA Starter Culture Microgrant, this event brought together Boston-area scientists and virtual attendees to update them on recent genome engineering tools, to give early career scientists and first authors an opportunity to present their research, and to make these talks available free of charge to a worldwide audience.

The symposium featured keynote speakers Benjamin Kleinstiver, Massachusetts General Hospital and Harvard Medical School, and Julia Joung, Whitehead Institute, along with presentations from nine PhD students and postdocs on their recently published work. The symposium was highly successful with approximately 200 in-person attendees, 385 virtual attendees, and more than 800 views of the recording across the globe. Positive feedback from attendees focused on the lack of fees, availability of a recording for those in distant time zones, and advertising through GSA. Critical feedback centered on a perceived preference for in-person attendee questions over virtual.

This symposium was the culmination of five years of grassroots efforts by Boston-area scientists to stay on top of cutting-edge genome engineering techniques. Originally organized as an in-person journal club at Harvard Medical School, the virtual Genome Engineering Seminar Series (GESS) was created to mitigate COVID-19 social distancing policies. GESS is a free weekly seminar in which first authors present their recent paper or manuscript live over Zoom. Running since 2021, GESS has had more than 100 speakers and over 3,000 cumulative attendees from more than 51 countries.

Additionally, GESS provides leadership opportunities for early career scientists as seminar organizers. The program was initially established by Justin Bosch and Tracy Zhang, and the current GESS organizers are Ferreira Da Silva, Viswanatha, Hassan Bukhari, and Nouraiz Ahmed.

By hosting the symposium both in person and via Zoom, we eliminated most expenses typically associated with registration and travel for attendees. Given Boston’s concentration of groups involved in the development of genome engineering methods, it was practical to extend invitations to local experts to present in person. Therefore, our symposium format greatly reduces barriers for scientists to both present and attend. We hope to make this symposium an annual event with its hybrid format serving as a model for other research areas.

You can learn more about GSA’s Starter Culture Microgrant Program on the GSA website. Applications for microgrants are accepted on a quarterly basis.

Beyond understanding the admixture process behind the African American population, this model could help in uncovering African Americans’ genealogical fingerprint.

We often look to the past to understand the present. Many Americans can trace their genealogies to the 1600s, but for the African American population, understanding of our past is often halted in 1870. This “brick wall” in genealogical history is the first time most African Americans were counted in a census; before then, their enslaved African ancestors, who were forcibly imported as part of the transatlantic slave trade, were recorded as property either under their enslaver’s names or as numbers.

Now, genetic explorations of ancestry are chipping away at that brick wall. A new study by Mooney et al. published in the July issue of GENETICS can move African American genealogical understanding beyond percentages of African and European ancestry—to individuals.

Genealogical Recovery

Population genetics defines genetically admixed populations as the result of two or more source groups combining to make a new group. This new population’s ancestry will have multiple sources due to the continued genetic mixing within itself and with the source populations. The mathematical framework described by Mooney et al. considers admixture from a genealogical perspective, measuring and counting genealogical contributions to answer the question: How many ancestors from each source population contributed to a modern descendant?

The current African American population of ~47.2 million is estimated to hold some 15–25% European ancestry. Mooney et al. report that, across a range of genealogical combinations in their model, a random African American born between 1960–1965 can expect an average of 51 European or European American ancestors and 314 African ancestors over a 14-generation span, from the founding of the African American population in 1619 to the birth of the focal generation in the 1960s.

“This project has two main components,” states Noah Rosenberg, Professor of Biology at Stanford University and senior author, “One is we’re asking a new question about studying genealogies in admixed populations. We’re trying to pose the question of ‘how many individuals does that admixture represent?’”

Lead author Jazlyn Mooney, Assistant Professor of Quantitative and Computational Biology at the University of Southern California, adds that the second component of the study lies in its application—particularly to the focal population: African Americans born between 1960–1965. “A lot of the information that we’re getting about these genealogical ancestors we’re not able to recover from records.” This information is as basic as the numbers of ancestors. Mooney adds that, while the 1870 census may give some genealogical information from that period, it reports information about the already established African American population—not African ancestors. The new study focuses on uncovering information about those African ancestors: how many are there and from which generations.

To fill in some of the missing information about individual African ancestors, Mooney and colleagues built a mathematical model based on available African American genetic ancestry. They hoped to lift the veil on the genealogical and admixture history of the African American population.

To constrain the model, the authors broke the population history from 1619 to 1965 down into three demographic epochs defined by genetic data and major demographic milestones. The first epoch (1619–1808) includes the founding of the African American admixed population, with the second epoch (1808–1865) extending from the end of legal importation of enslaved African captives through the American Civil War. The second epoch shows reduced African genealogical contributions and increased European and European American genealogical contributions. The third epoch (1865–1965) begins with the end of legal enslavement and shows a reduction in European and European American genealogical contributions alongside the already low African contributions from the second epoch. This resulted in more African Americans forming deeper genealogical ties within the established African American population.

This study “gives you some sense of how many people were ancestors from Africa and survived the Middle Passage,” states Mooney. “You’re likely not going to find any sort of written information about these individuals at all.”

The study sits at the intersection of family structure, genealogy, and demography. While a mathematical model only gives a glimpse of the historical implications for the admixture events that have contributed to the African American population, it gives a much-needed new tool for thinking about demographic history.

The study also comes at a time when population geneticists are thinking about the complexities of terms like admixture and the continental labeling of ancestry—and how misreadings of these terms sometimes appear to bolster the long-repudiated idea of biological races in humans. Handling editor John Novembre adds, “In the current study’s context, the individual ancestors came from distinct parts of the globe, so the framing used has traction and relevance for the problem at hand. It is important, however, to remember that the historical ancestors came from various regions within the large landmasses of Europe and Africa, and neither of those represent monolithic units of human ancestry.”

Future applications of this mathematical framework include adding additional source populations such as Indigenous populations. The authors can also explore partitioning ancestor contributions based on sex to find the relative prevalence of male or female genealogically contributing ancestors. A version of this model can even answer similar demography questions for non-human admixed populations.

About the Author:

Tyler Jones is an entomologist, freelance science writer, and the current Coordinator of the SciCommers Science Communication Collective. She is an experienced science communicator in person, print, and multimedia who explores how storytelling builds community and fosters connection. When not writing about science, Tyler teaches stand-up comedy at her local improv theatre.

This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee.

By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was “jiggly” and had little motor control. As he got older, new symptoms emerged, including seizures, sugars in his urine, and an inability to produce tears. Bertrand’s parents spent countless hours consulting with medical specialists to track down the cause of Bertrand’s illness. In 2010, when he was four years old, the Mights enrolled Bertrand in a clinical trial of a then-novel technology: DNA exome sequencing. Sequencing revealed that he had inherited two different nonfunctional copies of a gene called NGLY1.

With that DNA test, Bertrand became a medical and scientific pioneer—the first patient ever diagnosed with NGLY1 deficiency. But because the disease is so rare, there were no therapies that could cure or treat it at its source; doctors could only try to relieve Bertrand’s symptoms as best they could.

To raise awareness, Bertrand’s dad, Matt Might, published a post on his popular computer science blog detailing the family’s diagnostic odyssey. Over time, the Mights connected with dozens of families also coping with the condition. Interestingly, the collection of symptoms varied quite a bit from case to case,
and genetic sequencing helped a number of families finally put a name to their diseases.

Doctors learned more about the disease with every new patient that came forward. But to really understand how the loss of NGLY1 can cause devastating symptoms throughout the body, scientists would have to take a different path: studying NGLY1’s function in the body at a molecular level. They needed to explore the biochemistry of the protein that NGLY1 encodes, find other molecules that interact with it as it performs its functions, and map out the ripple effects of losing the gene. To capture that level of detail requires controlled studies at a huge scale, something only possible in fast-reproducing research organisms, such as fruit flies and nematode worms.

The not-so-lowly worm

Around the time that doctors were beginning to recognize the clinical effects of NGLY1 deficiency in people, a researcher named Nicolas Lehrbach was making his own surprising discovery about NGLY1, in a different context. Now an assistant professor at Fred Hutchinson Cancer Center, Lehrbach first stumbled across NGLY1 while doing his postdoctoral research at Harvard Medical School.

Lehrbach studies how cells take out their molecular trash, or, more specifically, he studies how cells can compensate when their trash-disposal system isn’t working. When we talk about cellular “trash,” generally that means protein molecules that are damaged, misfolded, or otherwise no longer needed. The cellular machine that breaks down these proteins is called the proteasome. Lehrbach studies the proteasome in the tiny nematode C. elegans—colloquially called “the worm” in biology labs.

“If you think about the fundamental machinery needed by every cell, whether it’s in a human or a worm or a fungus or a plant, there are some basic processes that are simply required for life,” Lehrbach explains. “The underlying molecules that do those jobs are almost the same in any living thing.” The proteasome does one of those essential jobs required by every living animal cell. So by figuring out what molecules keep the proteasome humming along in worms, Lehrbach could also learn something about what makes the proteasome tick in humans.

Worms are inexpensive and quick to breed in the lab—a worm matures from embryo to adult in three days, and each worm produces about 300 offspring.This means that researchers can do thousands of experiments at once looking for rare mutations that affect some aspect of the animal’s development or behavior. Suppose you’re trying to understand how the nervous system develops. First, you would feed the worms a chemical that increases the chances of genetic mutations, and then you’d examine thousands and thousands of mutated worms to find the handful whose nerves didn’t develop properly. By analyzing the genes of those animals, you’d discover which genes contained mutations that caused the defect.

Lehrbach applied this approach to studying proteasome function. He designed a genetic screen to hunt for genes that, when mutated, boost the cell’s production of the proteins that make up the proteasome. “If the proteasome is not working well, one of the ways that our cells can cope with that is just to make more proteasomes to compensate,” Lehrbach says. His experiment revealed that the worm relies on a version of NGLY1 for that process.

“The power of that method is that it doesn’t presuppose any model or hypothesis about what kind of genes are going to be involved,” Lehrbach explains. Rather than choosing a gene and seeing whether it does something important, the researchers can do a wide-ranging search and see what turns up. “I would have never in a thousand years—if I were searching in a more targeted, hypothesis-driven way—I would never have thought the NGLY1 gene would have that role,” he says.

Proteasome failure is a hallmark of various human diseases, including neurodegenerative diseases like Parkinson’s and Alzheimer’s, but Lehrbach wasn’t narrowly focused on pathways involved in disease. The worm studies exemplify how expanding our knowledge of basic cellular processes can lead to unanticipated clinical benefits. “When you have a patient with clinical symptoms, but you want to get back to the molecular mechanism, that’s a really hard puzzle to solve,” Lehrbach says. “That clue from genetics, which really came out of the blue from doing a very open experiment, provided an insight that helped accelerate the process of understanding NGLY1 deficiency.”

Of flies and men

After receiving Bertrand’s genetic diagnosis, the Might family started a foundation, NGLY1.org. Through the foundation, they reached out to geneticist Clement Chow at University of Utah Health for help to uncover more information about how the lack of NGLY1 was making their son ill.

Chow’s lab studies protein misfolding and how the cell deals with incorrectly-folded proteins when they build up in a part of the cell called the endoplasmic reticulum. NGLY1 plays a role in clearing those misfolded proteins, and Chow set out to uncover exactly what that role is.

Using the fruit fly Drosophila in the lab, Chow and his colleagues genetically engineered different flies with different NGLY1 mutants, to see what effect each mutation would have on the fly. Some mutations might completely destroy the NGLY1 protein, while others might just make it weaker or less efficient at doing its job. Flies with mutations in NGLY1 had delays in development, and some died in the larval stage. Others matured to adulthood but still died sooner than normal flies.

Chow also investigated how the loss of NGLY1 changed the expression of other genes. Genes can be turned on or off, meaning they actively produce their protein or they lie idle. They can also be adjusted up or down, like twisting a volume knob on a stereo, so they produce a little more or less protein. Often, these adjustments are managed via biochemical feedback pathways in the cell. NGLY1 removes sugar molecules called glycans from various proteins, and when that function is lost, the excess of glycans alters the activities of those proteins. These changes can have a cascade of effects that lead to changes ingene expression. For instance, there is a protein called Nrf1 whose job is to turn on several genes that make components of the proteasome, to ramp up new production when it detects proteasome failure. It can do this only after NGLY1 removes a glycan from a key building block molecule in the protein, chemically changing its identity. Without NGLY1 there to strip off the glycan, Nrf1 can’t activate those genes, and the cell can no longer compensate for proteasome failure.

By comparing gene expression between healthy flies and those without NGLY1, Chow discovered that losing NGLY1 caused a drop in the level of a protein that helps make a sugar called GlcNAc. Adding and removing GlcNAc from proteins is one key way the cell directs their activity. Currently, GlcNAc is sold over the counter as a supplement. “What’s exciting about this is that patients had already been thinking about using this particular sugar,” Chow says. Because GlcNAc is easy to get, parents of kids with NGLY1 deficiency had tried it at home. “There had been anecdotes that it was providing relief, especially with tear production,” says Chow. When he gave GlcNAc to the mutant flies, they tended to live longer than those that didn’t receive the supplement. A clinical trial of GlcNAc eye drops in kids with NGLY1 deficiency is getting underway at Mayo Clinic to test how well the supplement performs at increasing tear production in these kids who have NGLY1 deficiency.

The GlcNAc discovery in flies not only helped explain how the supplement was helping kids with NGLY1 deficiency, but it was powerful in another way, as well: it validated the fly as a model of how NGLY1 was working in human cells. “That was kind of our first foray into thinking about NGLY1 and what we can do with the fly,” Chow explains.

The next step for the Chow lab was to understand how other genes interact with NGLY1, creating variation in the disease presentation. Among the patients with NGLY1 deficiency, the severity of symptoms ranged widely; for example,the second NGLY1 patient to be identified, Grace Wilsey, learned to crawl, talk, and follow simple directions, skills that Bertrand Might never acquired. Human NGLY1 patients are too few, and too genetically complex, to support clinical studies of genetic interactions that may provide clues to why disease presentation is so variable. Using fruit flies enables researchers to study thousands of animals from genetically controlled populations.

To look at how variants in NGLY1 interacted with other genes in the genome, Chow’s lab turned to the Drosophila Genetic Reference Panel, a collection of fruit fly lines that all carry slightly different genetic changes. The flies were bred from the same original population, so they mostly share the same genome, and each line’s genome sequence is well-documented. By disabling the NGLY1 gene in each different fly population, then documenting the number and severity of the symptoms, they uncovered a gene called NKCC1.

The fruit fly experiments were invaluable to test a large number of genetic interactions in a short period of time, but to fully characterize how the NGLY1 and NKCC1 proteins interact, Chow turned to mice. Experiments in mouse cells grown in the lab revealed exactly how NGLY1 chemically modifies NKCC1 to keep it working properly. “We started out with this very basic tool that fly genetics labs use all the time, which is a genetic screen, and they brought us all the way to thinking of finding defects in mammalian cells in a pretty quick order,” Chow said. “That tells us that the flies are modeling exactly the same thing we see in mice and humans.”

Studying mammalian cells or even human cells grown in a dish in the lab may sound like a more representative model for human disease, but these lab-grown cells can’t perfectly replicate what’s happening in a live animal. To understand the complex interactions between the many genes and proteins over the course of a life cycle, nothing can replace an intact, living animal, even if it’s a miniscule worm or a fruit fly. “There are certain processes, like communication between different types of cells within an organism, that are impossible to model with a layer of cells in a dish, which are all undifferentiated and more or less identical to one another,” Lehrbach says.

And while a worm or a fly can’t exhibit speech delays or intellectual disability, the genes responsible for these issues in people perform largely the same functions on the cellular level in all creatures. “These are mutations in basic housekeeping genes that every organism needs to have functioning,” Chow said. “While their disease may not perfectly match what we see in humans, the cellular process and the biological process is nearly identical in flies and humans, so that makes it a pretty good model for disease.”

For Bertrand Might, genome sequencing revealed the cause of his disease, marking the end of the family’s diagnostic odyssey. At the same time, the diagnosis was only the beginning of a new odyssey: a quest to find a treatment that could compensate for the loss of NGLY1. Sadly, there’s not yet any cure for
NGLY1 deficiency, nor a treatment that directly addresses the genetic cause of the disease. But ongoing research to understand all the different ways that NGLY1 manages important cellular functions is leading to interventions that can lessen the impact of losing NGLY1. While Bertrand himself died in 2020, the research he inspired—including a Precision Medicine Institute at the University of Alabama at Birmingham, which Matt Might directs—aims to someday help other children with NGLY1 deficiency and other rare disorders to live longer, healthier lives.

To learn more about the ways that model research organisms contribute to the study of rare disease, visit any of the links below.

1. GENETICS: https://academic.oup.com/genetics/article/214/2/233/5930504
2. Undiagnosed Diseases Network: https://undiagnosed.hms.harvard.edu/
3. MARRVEL: http://marrvel.org/
4. ModelMatcher:  https://onlinelibrary.wiley.com/doi/10.1002/humu.24364
5. Rare Diseases Models and Mechanisms Network: http://www.rare-diseases-catalyst-network.ca/
6. The Jackson Laboratory Rare Disease Translation Center: https://www.jax.org/news-and-insights/2022/December/jax-strives-to-advance-rare-disease-research-andreatment-options
7. Zolgensma for Spinal Muscle Atrophy: https://www.pennmedicine.org/news/news-releases/2019/may/zolgensma-based-on-delivery-system-discovered-by-penn-gene-therapy-pioneer
8. Zolgensma for Spinal Muscle Atrophy:   https://www.sheffieldchildrens.nhs.uk/news/edwards-story-the-world-is-his-oyster-after-gene-therapy-treatment/ 
9. Charcot-Marie-Tooth: https://www.jax.org/news-and-insights/2018/August/kathy-morelli-finding-cures-for-rare-diseases 

Carla Bautista Rodriguez is a PhD candidate in evolutionary biology at Laval University (Canada) and a member of the Genetics Society of America. She is also passionate about outreach and scientific communication. She is an active member of various American and Spanish societies that are dedicated to bringing science to the general public.

The GSA multilingual seminar in Spanish, titled “Challenges of Doing and Communicating Science as Spanish Speakers,” was held on September 3, 2021. As revealed by the participant survey conducted during registration, the participants’ origins were very diverse, including many non-Spanish-speaking countries, which indicated the active participation of professionals working in their non-native tongue. Among the outstanding areas of expertise of the participants were pharmaceuticals, agriculture, government jobs, education, and research. This wide range of topics ensured a very fruitful seminar.

The need to meet

This survey revealed shocking perspectives on Spanish speakers in the field of science. While 50 percent of respondents claimed to have an advanced level of English, more than 75 percent admitted to feeling afraid or ashamed when expressing themselves in their professional field. Despite these concerns, more than 80 percent of participants reported making presentations in other languages, and more than 50 percent reported staying abroad. Most respondents also expressed interest in finding a job in countries where their mother tongue is not spoken.

Our panelists

The Spanish seminar was led by 3 incredible panelists with very diverse and interesting profiles. With a more industry-oriented profile, Roberto Carballido is a talent scout and defender of diversity who works for Eli Lilly and Company. A professor at the State University of New York at Buffalo, Javier Blanco is a renowned researcher in the fields of biochemistry and pharmaceutical sciences. And finally, with a biochemical background, Attabey Rodríguez Benítez is as an important science popularizer and editor of SciShow, a YouTube channel.

Challenges as Spanish speakers

We should normalize the experience of not being understood when we arrive in a new country. Consistency and practice are key. After years of dedication to learning a language, feeling disappointed when you do not achieve fluency in practice is normal. In addition, we have to consider the cultural shock of experiencing all these feelings alone, without the support of family and friends. Furthermore, researchers face constant pressure due to the highly competitive and demanding research environment. Therefore, finding a secure network where you feel comfortable is crucial. 

Practical strategies for overcoming the English language barrier

As part of the seminar, we collected great tips from our panelists on speaking and interacting in English:

1. Outreach is a good way to learn English because you have to explain difficult concepts in an easy way.
2. If you feel that the language barrier is endless in the first instances of your scientific journey, look for other ways to communicate. Your skills can be displayed in many ways: scripts, graphs, techniques, new methods, etc.
3. Find a community where you feel safe. The scientific community is likely multicultural in any country. You will interact with many people who are probably going through the same difficulties as you.
4. Because of #3, native English scientists are used to many different accents, errors, vocabulary, etc. Accept that your accent is not native but still perfect. Your accent is what it is, and it’s nice because it’s a mixture of your native culture and your new culture. Enjoy that distinction! Do not be afraid! Stop looking for perfection. The important thing is to communicate effectively.
5. If you feel that someone does not understand you, ask: have you understood me? Likewise, when you do not understand, ask your interlocutor to repeat and speak more slowly.
6. There are many people who want to help, but they will not help you if you do not raise your hand. They won’t read your mind. Ask For Help. You will be surprised by how they help you.
7. Use tools that make your day-to-day life easier—for example, Grammarly and Wordtune, which are web browser extensions that help correct your texts. (I’m currently using them as I write!)

Why should we continue speaking in Spanish about science?

Transmitting and communicating what we do in our native language is important. English-speaking children are more likely to become passionate about science because they have been exposed to more scientific content in English, the most used scientific language. We, therefore, have to end this bias! We need more resources in Spanish to create scientific interest among young Spanish speakers. The only ones who can do it are scientific Spanish speakers because they can translate science. Furthermore, during the pandemic, there was a growing need and demand from the general population for tools that would allow them to understand what was happening. Let’s take advantage of this opportunity and inform the public about our findings. 

Model your professional career from now on

Finally, we had a conversation more oriented to each participant’s area of expertise, where they shared valuable advice and resources (Table 1). We hope you find all of this information useful, and we especially hope to see you at future GSA seminars! (You can rewatch the webinar here.)

Notes:

1. a. https://college.uchicago.edu/academics/science-communications-courses
   b. https://libguides.ncl.ac.uk/sciencecommunication
2. https://www.aaas.org/programs/mass-media-fellowship
3. a. https://genetics-gsa.org/career-development/early-career-leadership/
   b. https://elifesciences.org/inside-elife/bd8565f0/elife-ambassadors-an-invitation-to-take-part-in-2022
   c. https://www.ascb.org/associated_committee/postdoc-graduate-student-compass-committee/
   d. https://www.aquinoscuidamos.org/
4. https://www.linkedin.com
5. https://www.sacnas.org/
6. http://jobsontoast.com/how-to-convert-a-scientific-cv-into-a-business-cv/
7. a. https://app.grammarly.com/
   b. https://www.wordtune.com/
8. https://getpocket.com/es/

Why were you motivated to write this kind of paper?

Doc Edge: Brandon and I were at a small scientific meeting in Santa Barbara last spring, and he approached me with the idea to write this piece. I actually hadn’t really seen the movie at the time; I remember my AP Biology teacher putting it on one day after the AP exam, but I don’t think I paid much attention. Brandon might have been disappointed in me for being uncultured, but I went home and watched it, and I knew immediately that I wanted to write about Gattaca. I realized that so many of the things I care most about in my research and teaching show up in this movie in one way or another. In my research, I’m interested in complex trait genetics and in forensic genetics. I also teach research ethics, and in all my classes—even my statistics and genetics classes—I make sure students learn something about the history of eugenics. It’s all there. 

C. Brandon Ogbunu: Oh, this one goes back. I first saw Gattaca during my first year in college, and it had a very large effect on me. It was absolutely my introduction to thinking about issues at the intersection of genetics and society. Since then, I’ve always wanted to engage this topic in a formal, technical way. In some ways, my education over the past few decades has prepared me for this.

I think the meeting at The Foundations Institute in Santa Barbara, called “Reimagining the Central Dogma,” was the perfect place to crystallize these sorts of ideas. The workshop had several leading thinkers speak on issues related to genetics, genomics, and evolution, and we had this rich conversation about many aspects of what we are missing from classical depictions and interpretations of the central dogma. The joke is that Doc and I were stuck having lunch together one day, and I introduced the concept of thinking about the film from this lens. On the long drive to the airport, we really began to flesh out the idea for a paper. 

How would you describe the collaboration? 

Doc Edge: I’ve admired Brandon’s writing from afar for a long time, so it was a privilege to be able to work with him. At the beginning of any collaboration, there is a period when you wonder whether it’s going to work, but in this case that period was short. We had a call where we talked through the points we wanted to hit, and then we really flew—we had most of our first draft within days. Brandon is a really generous collaborator, and I’m grateful he wanted to write this with me.

C. Brandon Ogbunu: Doc is truly one of the best young population geneticists that I know. I’ve seen his work and even taught from his new statistics textbook. What inspires me about Doc is his combination of domain knowledge, technical acumen, and understanding of how the world works. He was someone I could talk to about all aspects of the project. In particular, Doc’s work on molecular forensics piqued my interest. I saw him give a stellar talk on the topic, and I knew then that I wanted to work with him on something having to do with science and society at some point. And we found our calling on this film. It’s been a joy. 

What is your general take on modern genomic technologies like facial reconstruction and polygenic embryo selection? 

Doc Edge: I’d distinguish modern genetic technology in general from the specific examples mentioned. Genetic technology in general is full of amazing achievements, like modern sequencing and CRISPR gene editing. But in any situation where there is a strong desire for a technical fix to a complicated problem, there is a danger of acting too hastily or overselling—even when all actors have the very best intentions. I feel like my role as a geneticist is to try to figure out what is possible now and what might be possible in the future—and importantly, to do my best to think through some of the implications and state them as clearly as possible. The conversations are bigger than me and require expertise beyond what any one person has.

C. Brandon Ogbunu: Correctly, we tend to separate the ethical issues from the technical ones. That is, whether we should embrace a new technology is its own discussion. But what I often say is that sometimes the technical is the ethical. A lot of these technologies, that institutions and people are eager to put into action, are based on false promises with huge technical and scientific challenges. For example, polygenic scores are a powerful new tool to determine risk for certain complex phenotypes. But are they loaded with so many caveats that their general use for embryo selection cannot be justified. 

Are you a fan of science fiction? What are some of your favorite stories? 

Doc Edge: I’m inclined to say something like “as much as the next person,” but that’s probably only true if the next person is a huge nerd. I don’t go to conventions or anything, but I do enjoy sci-fi. Last year I read Le Guin’s The Dispossessed for the first time and really enjoyed it.

C. Brandon Ogbunu: I’d say that I’m somewhere between a fan and a superfan. As in: I don’t quite go to conventions and subscribe to zines, but I read many novels and have watched many films. My love of science fiction is a nontrivial part of my identity.

As far as favorites…there are so many. I’m especially inspired by Black science-fiction writers like Octavia Butler and Samuel Delaney. But I embrace other classics, like the works of Ursula LeGuin, Frank Herbert, and Phillip K. Dick. 

And leaving books, I confess that I’m a fan of the big franchises like Star Wars and Star Trek. But one of my hobbies is to find random weird science-fiction that speaks to me. For example, Fantastic Planet is a relatively obscure French animated science-fiction film that I love. I think different cultures and corners of the world have interesting things to say about society and the future. 

What do you think about the bridge between science and science fiction?

Doc Edge: I’m not sure how to answer in general, particularly given how diverse the approaches to science within sci-fi are. I’ll say that in my favorite sci-fi, the science being fictionalized might be interesting in itself, but the point of it is to expose something about our own world. That’s certainly true of Gattaca.

C. Brandon Ogbunu: The “science” in science-fiction has always been a tricky one. Like we suggest in the paper, science-fiction doesn’t need to be technically accurate to be a very effective piece of work. I find that when scientists criticize science-fiction on technical grounds, they are mostly missing the point. Of course, there are instances when the scientific errors are so egregious that it creates a plothole, but this is usually not the case. And I think scientists should embrace the fictional world as an experimental playpen for ideas that are too risky or bold to test in the real world. I think Gattaca was an example of this done very well. Our new work demonstrates what happens when art decides to explore ideas that society isn’t mature to grapple with yet. My hope is that this interface between science and popular culture is something that grows. 

Jadson C. Santos (Jall)

Career Development Subcommittee

University of São Paulo

Research Interest

I have carried out research in various scientific areas—among them, human genetics, bioinformatics, structural biology of proteins, and molecular immunology. I’ve always been passionate about science, but the molecular world sparked my imagination and attracted me more than any other area.

Currently, as a third-year PhD student in genetics, I integrate computational and experimental methodologies to understand the impact of pathogenic mutations on the 3D structure of proteins important to the immune system. In parallel, as part of my MBA in project management, I conducted research on leadership and working in scientific teams to understand the main interpersonal challenges that those teams face in scientific projects.

As a PhD-trained scientist, you have many career options. What interests you the most?

As a scientist, my main interests are in transdisciplinary research, which integrates different areas of knowledge in the search for innovations and discoveries that can solve complex world challenges, such as biodiversity loss, species extinction, the climate crisis, education, water scarcity, and global health.

To this end, I find myself applying the transferable skills I’ve learned during my scientific journey—combined with the management and leadership skills I’ve gained over the past four years—to connect knowledge and people with a common purpose. More specifically, I’m interested in working in management positions of international scientific societies to increase the visibility of science and its social impact, as well as catalyze scientists’ potential to innovate and discover “new worlds” through well-designed and well-executed projects.

Additionally, I am deeply interested in work that involves the career development of scientists and early career professionals. Therefore, since 2020, I have been mentoring undergraduate and graduate students on skills and career development in my country. This activity is a service of great social value and brings me immense satisfaction in knowing that I am directly contributing to the lives and careers of other scientists along my journey.

As a project consultant and trainer in project management, leadership, and communication, I aim to develop professional activities for scientists and research groups around the world. I am deeply fascinated by the academic/scientific environment. In my career vision, I will have the opportunity to visit different research groups and universities around the world, witnessing firsthand the places where knowledge arises while contributing to this process throughout my career. In short, I see myself as a scientist working to create the project, management, and leadership structures that can catalyze the results of scientists and generate impact beyond universities and research institutes. Science plays a central role in the development of the world and being involved in this development inspires me to do my best daily.

In addition to your research, how do you want to advance the scientific enterprise?

The collaborative nature of my PhD research made it clear to me that we need to continuously improve our interpersonal and intercultural skills. In most scientific and technical fields, more than 90 percent of research project studies and publications are collaborative, with collaboration skills being a prerequisite for scientists. Also, the increasing internationalization of scientific research makes such skills crucial in this environment.

In recent years, I’ve focused on training that can enhance my management and leadership skills to make a solid contribution to science by helping scientists strengthen their collaborations. This investment in learning outside academia was crucial to my understanding of the complexity of the challenges we face not only as scientists but also as individuals with different cultures, values, and life/career goals.

My broader career goal is to contribute to the creation of a more collaborative and productive scientific culture. Such a challenge requires a broad integration between science and other areas of knowledge. Likewise, it is essential to understand the dynamics of research teams and groups—an understanding that is facilitated when we live in this scientific environment. For this reason, my scientific journey forms the basis of my career, as it allows me to deeply understand the day-to-day challenges that scientists face in their research. I am also developing my collaborative knowledge and skills by writing a newsletter on leadership and collaboration in the research environment (with 8,000 subscribers, mostly graduate students and postdocs) and managing a community of more than 900 scientists and professionals interested in collaboration in life sciences. Being part of GSA’s Early Career Leadership Program is therefore a great opportunity for fostering a collaborative environment and improving my skills in this area.

As a leader within the Genetics Society of America, what do you hope to accomplish?

Before officially joining the program, I was already collaborating with GSA. In 2021, I was an organizer and moderator of the Portuguese Multilingual Seminar Series, along with two other Brazilian partners. At another scientific event, I hosted a virtual room for Portuguese-speaking scientists to integrate them into the event via their native language, thereby strengthening networking.

As co-chair of the Career Development Subcommittee, I look forward to continuing to learn from my partners inside and outside the subcommittee. Additionally, I intend to bring to our projects a vision from beyond academia that improves existing processes to better support the professional development of the scientific community.

The events that I have already organized together with the subcommittee members have proven relevant to the scientific community, especially early career scientists. I often receive positive feedback from my professional connections, informing me how crucial our content was to their lives and careers. This positive impact on the community motivates me to continue improving my ability to create value through my activities at GSA.

In the long term, I intend to broaden my experience in management and leadership in a multicultural environment and establish long-lasting collaborations with my Early Career Leadership Program partners. These long-term collaborations will be essential, allowing me to continue learning, engaging with the GSA community, and generating value for early career scientists and society.

Previous leadership experience

• Founder and Mentor for Career Development, SSK Mentoring, 2020 – Present
• Community Manager, Leadership and Collaboration in Science (Virtual Community), 2021 – Present
• Advisor, Mendeley Community, 2020 – 2021
• Tutor, theVirtual University of São Paulo, 2019 – 2020
• Expert Volunteer, Science Buddies Ask an Expert Program, 2018 – 2019

You can contact Jadson C. Santos (Jall) on LinkedIn, Instagram, or Twitter. You can find his newsletter on LinkedIn here.

Taking direction from evolution

One feature of evolutionary biology that has always intrigued me is the preponderance of “laws.” That is, not “laws” as in Newton’s laws of motion, but less formal ones—analogies and principles that describe a theoretical idea. Many do not have the term “law” attached to them but are laws nonetheless: terms and phrases that describe presumptive fundamental evolutionary phenomena, like the Red Queen hypothesis, Muller’s ratchet, and punctuated equilibrium.

I have a longstanding curiosity about the origins and role of these laws in biology; I think some of them stick around because they help communicate complicated ideas, even if they’re arbitrarily constructed or imprecise.

Dollo’s law is one of my favorite examples:

“An organism is unable to return, even partially, to a previous stage already realized in the ranks of its ancestors.”

In the Blind Watchmaker, Richard Dawkins interpreted it as:

“….just a statement about the statistical improbability of following exactly the same evolutionary trajectory twice (or, indeed, any particular trajectory), in either direction.”

Or even more casually (as I say it):

“It is difficult for an improbable event to happen and then un-happen in the exact same way.”

Essentially, Dollo’s law speaks to the improbability of “reverse evolution.”

Now before you jump in, I know, I know—there are no real directions in evolution. So what am I getting at?

Sure, there is no true “forward” or “backwards” in evolution, and the general misuse of the language of progress has been costly to evolutionary biology. Too many of us (even practicing biologists) tend to erroneously discuss or think about evolution as being a progressive force.

That said, we can discuss direction when we are talking about the evolution of very specific traits in specific settings. For example, if we talk about a population of bacteria evolving resistance to an antibiotic, we can talk about evolving towards resistance (for conversation purposes, at least). “Reverse,” in this situation, would be from a resistant form “back” to a treatable form.

Why is this important?

Well, one of the proposed strategies for preventing the evolution of antibiotic resistance is to drive evolution “backwards.” If a population is resistant to available antibiotics, perhaps we can use drugs to encourage that population to evolve “’backwards” to its more treatable form. Clinicians could then use currently available drugs to treat the newly-non resistant infection.

More recently, scientists have used the term “steering” to talk about ways to manipulate populations of resistant organisms towards being treatable. Physicists and physicians have even used the rules of quantum physics to help think about ways to control the evolution of resistance.

But these applications aside, basic questions surrounding the forces that craft reversal are central in evolutionary theory. The answers are relevant not only for phenomena like antibiotic resistance, but also for other questions about cancer, resistance to butterfly toxins, and more. This even has implications for how we are thinking about genetic modification (GM): when we engineer a mutation into a crop for agricultural purposes, can we be sure that it won’t “un-evolve” that mutation “backwards” towards the non-GM crop?

Asked differently: can evolution do the moonwalk?

What is the moonwalk?

The moonwalk was made famous by Michael Jackson, but it was invented by Shalamar’s Jeffrey Daniel in 1982. We might take it for granted now, but when Daniel first pulled it off, it looked like a special effect. People thought that a string must have been pulling him because he seemed to be moving backwards just as seamlessly and smoothly as one can move forward.

So what does the moonwalk have to do with molecular evolution?

We can ask how evolution might move backwards—just like Daniel’s dance. Equipped with population genetic theory, we can examine the particular forces and conditions that facilitate that backwards movement.

Microbial moonwalking

I have previously published on reverse evolution in the context of antimalarial resistance. In that 2016 study, I found that the surprisingly large impact of certain compensatory mutations limits the ability of a population of resistant malaria parasites to become treatable again. Since then, I have remained curious about other ways to test Dollo’s law: what other places, models, and systems can we use to examine reverse evolution?

Luckily, other scientists I respect and admire had similar curiosities. 

Dr. Pleuni Pennings is an evolutionary computational biologist who helped to pioneer the fusion of classical theoretical population genetics with very modern questions in HIV drug resistance. Her work had a very large impact on my career when I was learning population genetic approaches to thinking about disease evolution during my postdoctoral training. Although we’d already collaborated on several different educational programs and communication efforts, I had never had the pleasure of working with her on an actual science project until she approached me in 2019.

At that time, Dr. Pennings was in the process of establishing a collaboration with Dr. Ruth Hershberg, an eminent microbial evolution expert at Technion-Israel Institute of Technology. Dr. Hershberg had recently published a study that examined the results of experimental evolution in E. coli. Together, they were interested in exploring the conditions that facilitated reverse evolution in experimental populations of E.coli, and they brought me in on the question.

Over the next year or so, we discussed and designed several projects in the arena, but we decided that what we needed first was to use tools in theoretical and computational biology to ask some basic questions:

• How does mutation rate influence the probability of reverse evolution?
• How do the number and phenotypic effect of compensatory mutations influence the probability of reverse evolution?

These are two highly specific but very important variables to investigate for several reasons. For one, Dr. Hershberg had performed experimental evolution in background strains of E.coli that varied in their mutation rate. So we had the potential to compare computational results to experimental findings, which is an important point. Our collaboration provided the opportunity to use models and theory to explain experimental results. Plus, the questions surrounding the effects of mutations were compatible with prior work of mine about the nature and magnitude of compensatory mutations.

To ask these questions about reversion, here’s what we did:

• We created a “computerized world” where a population of bacteria had evolved resistance to a drug. In this situation, resistant variants carried a fitness cost in “drugless” environments, meaning resistant bacteria had high fitness in the presence of drug, but low fitness in the drugless environment.
  
• We then took the drug away (“drugless” environment) and asked whether the population of resistant bacteria would evolve “backwards” towards the wild type ancestor. We might expect this is because wild type had higher fitness than the resistant allele in the “drugless” environment.
  
• We specifically tuned two aspects of evolution in the “drugless” environment: mutation rate and the effect of compensatory mutation, meaning the degree to which mutations compensated for resistance.

The results were fascinating:

• The probability of reverting back to wild type was powerfully influenced by both the mutation rate and the effect of compensatory mutations. At very low mutation rates, compensatory mutations rose to fixation and no reversal to the wild type occurred. At very high mutation rates, compensated reversal emerged. Bacteria evolved two mutations: first the compensatory mutation, then the reversion to the wildtype. Intermediate mutation rates, however, displayed the proper conditions for reversal: the wild type mutation arose early enough that it could dominate a population (Figure 1).
  
• A lot of the findings really did boil down to how strong the compensatory effects were. For mutations that compensate for the cost of resistance: how many are there? Do they fully or partially compensate?

• Critically, the simulation results helped make sense of published experimental results. In these studies, reversal was observed when mutation rates were high. Our modeling result demonstrated that compensatory mutations in the experimental populations likely do not fully alleviate costs associated with resistance.
  
• This is a very big point: our simulations have diagnostic utility. From them, we can walk into experimental data and make sense of them.

In sum, the findings demonstrate how reverse evolution in the context of drug resistance is sensitive to population genetics particulars. 

Why do we care?

For one, simply saying that reverse evolution is unlikely might not be wrong, but it is…incomplete. Population genetics can add color and rigor to this circumstance, so moving forward (no pun intended), all discussions of reverse evolution should be framed in terms of a particular population genetics setting.

Secondly, these results can inform modern conversations around how to steer the evolution of drug resistance. Perhaps we can rationally manipulate populations towards resistance or susceptibility using drugs of various kinds.

So, in the end, we can ask the bigger question:

Can evolution do the moonwalk?

The answer is “Yes, it can”—but the mutation rate and other properties of the context have to be just right.

And this is where the connection between the biology and the dance analogy emerge: you have to be a pretty creative person to come up with something like the moonwalk. But you can’t be too absurd. The innovative step that gave us the moonwalk was the product of an imagination with the right mutation effect size—one that imagines us moving backwards, against our intuition, but still right in rhythm.

Sure people might have been confused by the dance at first, but they will eventually realize that maybe their imaginations were too small and that there is no real forward and backward in dance—just like in molecular evolution.

I am a former women’s NCAA swimmer, and I support Lia Thomas.

Guest post by Sam Sharpe PhD.

interACT: Advocates for Intersex Youth is the oldest and largest nonprofit dedicated to advancing the legal and human rights of people born with intersex traits. Founded in 2006, interACT oversees the largest youth-led intersex advocacy group in the United States, is at the forefront of intersex litigation, and regularly advises public and private entities on how best to support the needs of intersex people. interACT’s mission is to put an end to non-consensual, medically unnecessary surgeries performed on intersex children in an attempt to erase their intersex traits and make their bodies conform to society’s perception of what a “normal” body is supposed to look like. 

Education and raising awareness about intersex issues is also a big part of what we do at interACT. Last year, we partnered with GSA and pgED to co-present a webinar discussing the relationship of sex and genetics, the long history of sex testing in athletics, and how these practices still have lasting impacts today. As of April 2022, at least 10 states have implemented legislation explicitly banning transgender youth from participating on sports teams that are in alignment with their gender identity, and 15 states have banned trans youth from seeking life-saving gender-affirming health care. While these anti-transgender laws are explicitly designed to discriminate against transgender people, many don’t realize that they also affect intersex people. You can learn more about how on our website.

In this post, Sam Sharpe details the historical context for these pervasive laws and the bogus arguments that attempt to link high testosterone levels to an inherent increase in athleticism, but in reality, do nothing more than showcase society’s intransigent commitment to transphobia, intersexphobia, and the patriarchal policing of women’s bodies.  

-Bria Brown-King, interACT: Advocates for Intersex Youth

I am also a trans and intersex person, a lifelong athlete, and a biologist. I vehemently believe trans women belong in women’s sport, and I recognize that the backlash that accompanies any level of success by a trans woman athlete is part of a much larger history and context.  

Sex verification and suspicion  

Outrage and suspicion based on the idea that men are pretending to be women in order to dominate women’s sports goes back over 100 years. 

When women’s participation in athletics increased in the early 1900s, this created significant anxiety that the position of (white) men in society was being threatened and the (white) ideal of women as delicate, feminine, and passive was in jeopardy. These concerns ranged from the myth that exercise and sport could damage reproductive capacity to the belief that the strained facial expressions of women athletes during exertion were unfeminine and ugly. 

As women’s involvement in sports grew, and it became apparent that women actually can excel at sports without their internal organs falling out, suspicions arose that these fast, strong, muscular athletes might not actually be women. As a result, women athletes were required to bring “medical femininity certificates” to verify their sex to international competitions beginning in the 1940s and 50s.

In the 1960s, the success of the Soviet Union in women’s athletics increased anxieties about the “authenticity” of women athletes’ sex and the possibility that men disguised as women were competing in women’s events. The “medical femininity certificate” was replaced by a requirement that a panel of doctors examine the genitals of every woman competing in international athletic competitions. This was humiliating and short lived; it was soon replaced by chromosomal testing.

However, even chromosomal testing proved to be an ineffective method of “sex verification” because human sex comprises multiple traits which come in different combinations. From the late 1960s until 2000, this policy failed to identify any men pretending to be women, but it did identify, humiliate, and traumatize multiple intersex women athletes born with traits such as Complete Androgen Insensitivity Syndrome—meaning that they have XY chromosomes but no ability to respond to testosterone. Some of these athletes did not previously know that they were intersex and only found out upon their disqualification from competition for traits of which they had no prior awareness.  

After mandatory chromosomal testing was deemed unethical and traumatic for intersex athletes and abolished in 1999, the International Amateur Athletic Federation (IAAF) maintained the ability to perform selective sex testing, later reclassified as “hyperandrogenism testing,” on women athletes if questions arose about their sex. In 2018, after protests from disqualified athletes, the IAAF revised the guidelines around sex verification testing. The new guidelines only applied to a handful of track and field events and stated that women athletes with “testosterone levels equalling or exceeding 5 nmol/L who are androgen sensitive” would be excluded from participation. In 2019, this was further revised to apply only to women athletes with “testosterone levels equalling or exceeding 5 nmol/L who are androgen sensitive and who have XY chromosomes and testes.” Under the current policy, the same athlete could be considered a man while running the 400 meters but a woman while running the 200 meters, highlighting the inconsistency of this definition of sex.

Trans athletes and testosterone myths

There is no single, simple, or obvious way to decide who counts as a woman because human sex refuses to be divided neatly into two categories, as is demonstrated by 60 years of failed attempts by the IAAF (now known as World Athletics). Definitions and perceptions of sex and femininity are also deeply racialized. The project of sex verification in women’s sport was precipitated by anxieties about women’s athletics threatening white femininity, and the athletes who have been subjected to “selective” hyperandrogenism testing have disproportionately been women of color from Africa and Asia who do not conform to hegemonic standards of white femininity.

Although sex verification testing has been applied to cisgender women athletes at times, all transgender women competing in women’s Olympic events were required to maintain a total serum testosterone level of below 10 nmol/L for at least 12 months prior to competition from 2003 until the 2022 Olympics. All trans women competing in women’s events in the NCAA and international athletics have been subject to regulations requiring that they be on testosterone suppressing medication, which has been shown to reduce testosterone in trans women to at or below average levels for cis women within a year.

In 2021, the International Olympic Committee (IOC) released an updated framework to go into effect after the 2022 Olympics that removes restrictions on both intersex and transgender women athlete’s testosterone levels unless it can be specifically proven that their transgender or intersex status provides a consistent, specific, and unfair advantage in their sport. 

This framework is non-binding and some federations have already said they will not accept it, but it reflects the growing evidence disproving the widespread belief that higher endogenous (naturally-occurring) testosterone levels provide a consistent and meaningful advantage across sports. A 2014 paper by Healy et al. found that elite cis men and women athletes actually had overlapping ranges of endogenous testosterone. This demonstrates both that some elite cis men athletes have testosterone levels below the typical range for cis men—yet are still elite athletes—and that endogenous testosterone levels are not the sole or defining factor separating the athletic performances of elite cis men and elite cis women athletes.

The more inclusive understanding of sex diversity outlined in the IOC’s new framework also challenges the argument that trans women should not compete in women’s sport because they supposedly possess an innate and universal athletic advantage due to being assigned male at birth, regardless of their transition status. Diversity in sex traits extends beyond endogenous testosterone levels, and there are no specific physical traits that trans women have which no cis women have. There are some cis women who are tall and muscular, who can grow beards, who produce high levels of testosterone, or who have Y chromosomes. There is immense biological variation within the category of cis women—a category which includes many intersex women. There are multiple examples of transphobic attempts to point out women athletes who are believed to be trans based on their appearance when the women in question are actually cisgender. This is simply recapitulating the anxieties and surveillance of women athletes’ biology and adherence to standards of white femininity that lead to a century of failed attempts at “verifying” woman athlete’s sex status. 

Crucially, claims that trans women have a sports performance advantage and are taking athletic opportunities away from cis women are not borne out, as there are no examples of trans women being disproportionately dominant in women’s sports. 

What constitutes an unfair advantage in sport?

Related to this discussion is also the larger question of how fairness is defined in sport. There is an inherent level of unfairness in all sports, and decisions about what is fair are not always clear cut. It’s up to the governing bodies in each sport to decide what constitutes an unfair advantage, and these decisions are continuously being revised as technology and training methods evolve.

In 2022, elite athletes are not expected to have average physical characteristics—in fact, in many sports, it’s expected that they don’t. Most naturally-occurring physical traits, even extraordinary ones, are considered fair advantages. 

Scott Hamilton, an Olympic gold medalist in figure skating, had a brain tumor as a child that prevented him from growing for several years and reduced his adult height. Being small can be an advantage in figure skating, but Scott Hamilton isn’t considered a cheater because his childhood illness made him shorter. Being tall is an advantage in volleyball, but there was no outcry that three-time Olympic gold medalist Kerri Walsh Jennings had an unfair advantage because she is 11 inches taller than the average woman in the US. There has been extensive discussion about Michael Phelps’s extraordinary body, which includes long arms, a long torso, above average flexibility, and below average lactic acid production, all of which are considered fair advantages.

However, the exceptions to this overall acceptance and celebration of unique bodies in sport are women athletes with sex traits which are perceived as failing to conform to expectations of cisnormative white femininity. These exceptions include both trans women and the cis women of color who were disqualified from sporting events because their naturally high testosterone levels were deemed an unfair advantage: Pratima Gaonkar, Santhi Soundarajan, Caster Semenya, Pinki Pramanik, Dutee Chand, Beatrice Masilingi, and Christine Mboma.

By contrast, men athletes with naturally high testosterone levels are not subjected to sex verification and are not considered to have an unfair advantage. It is inconsistent and unscientific to claim that endogenous testosterone is the only naturally occurring physical trait which provides an unfair advantage in sport (and only in women’s sport) when every other naturally occurring physical trait variation, no matter how extreme, is a fair advantage.

There are also many accepted “fair” advantages in sport that are not naturally occurring physical traits. In elite athletics, it is considered fair for athletes that have access to higher quality equipment, the ability to train full time due to economic security, and the ability to employ a full team of professionals to maintain their body to compete against athletes without these privileges.

In swimming specifically, a $500 tech suit can provide both a physical and mental advantage that increases racing performances. High school swimmers who can afford tech suits have a known advantage over high school students who can’t, but this is considered to be a fair advantage by USA Swimming and by high school conferences. We aren’t seeing legislation proposed to ban tech suits in high school swimming though, we are seeing legislation to ban trans girls from competing in high school sports because this is ultimately about bigotry and not about fairness.

Actual issues of fairness in women’s sports include the lack of opportunities, support, regulation of coaching and medical staff (extremely apparent in the exposure of extensive sexual abuse within USA gymnastics), and financial payoff for women athletes, but these issues do not generate the same level of consistent media attention or public outrage.

New headlines; old bigotry  

The public commentary about Lia Thomas has been riddled with transphobia, dehumanization, and lies under the guise of concern about women’s sport. Coming out as trans, dealing with unsupportive teammates, physically transitioning and undergoing a second puberty while training as a D1 student athlete, and then winning an event at NCAA championships is an incredible achievement—one for which Lia has been thoroughly punished. Strangers set against her participation have fabricated lies about her times pre-transition, her level of dominance post-transition, and the details of her body. Strangers supporting her have argued that her failure to break the 500 Freestyle record or to win either the 200 or the 100 Freestyle at NCAA championships means she has the right to compete. Cis women have been allowed to dominate NCAA championships for decades, but Lia daring to swim fast enough to win one race has prompted headlines about “the end of women’s sport.” To borrow from trans cyclist Rachel McKinnon: Why should a trans woman’s right to compete in sports be contingent on her not succeeding?While transmen and nonbinaryathletes face transphobia, they are not subjected to the same level of scrutiny, criticism, dehumanization, and punishment. At the end of the day, this is and has always been about the cultural obsession with scrutinizing women’s bodies and the transmisogynistic insistence that trans women are always illegitimate, deceptive, and predatory. It’s always been about fear, disgust, and dehumanization of women who aren’t seen as compliant to narrow, racist, transphobic, and exorsexist ideas about femininity. It’s always been about the anxiety that if a woman is too good at sports, she can’t possibly, really, actually be a woman.

About the Author

Sam Sharpe graduated from Carleton College in 2014 where they earned a BA in Biology and competed on the swim team for four years. They are currently working towards a PhD in Biology at Kansas State University and have presented nationally and internationally on plant evolutionary ecology, increasing inclusion in STEM education, and understanding biological variation in sex and gender. Sam served in a leadership role for the transgender student organization Gender Collective for five years and is a current board member for InterConnect.