Four Women Who Made Major Contributions to Genetics and Medicine (Whose names you might not know)

Nettie Stevens: Discoverer of Sex Chromosomes

Women like Nettie Stevens, who were born in the early 1860s, didn’t have a plethora of career options to choose from. They could either be secretaries, or they could be teachers. Stevens went down the teaching route. What she really wanted to do, however, was continue her education. Eventually, at the age of 36, she saved up enough money from her teaching jobs, moved from Vermont to California, and enrolled in Stanford University, and later in Bryn Mawr college for her PhD.

Stevens entered the field of genetics at a time when the field was rapidly expanding. Mendel’s seminal work on the principles of inheritance had been rediscovered in 1900, and in a few short years, Thomas Morgan – who taught Stevens at Bryn Mawr – would go on to show that genes are carried on chromosomes. While this might seem unremarkable now, Morgan’s research provided physical evidence for the heredity described by Mendel. However, despite the increasing evidence that physical traits are determined by genes, scientists still believed that either the mother’s environment or the chemical balance of the cytoplasm of eggs determined sex.

Nettie Stevens’ research put the issue to rest. Stevens studied mealworms – insects that resemble garden grubs – and after spending endless hours peering through microscopes, found that during spermatogenesis, the 20 chromosomes of the mealworm form “9 symmetrical pairs and 1 unsymmetrical [pair] composed of [a] small chromosome and a much larger mate.” This asymmetrical pair, she observed, was replaced by a tenth symmetrical pair during the formation of egg cells. She also found that somatic (non-reproductive) cells of mealworms followed a similar pattern: 10 symmetrical pairs of chromosomes in females, and 9 symmetrical pairs and 1 asymmetrical pair in males. This discovery was conclusive proof that chromosomes – in the form of the X and Y chromosomes in most animals – were what led to sex determination, and not maternal characteristics.

Nettie Stevens unfortunately died of breast cancer at the age of 50, a mere four years after she discovered sex chromosomes. Her reputation – both then and now – does not match the significance of her research. Morgan, her mentor and professor, is considered the most influential figure in modern genetics and often gets credited for all chromosome-related discoveries. Morgan’s name appears frequently in relation to his research on chromosomes, but Nettie Stevens’ doesn’t.

Alice Ball: The chemist who developed a cure for leprosy

Alice Ball grew up around chemicals. Her grandfather, James Presley Ball, was a famous African American photographer. Chemicals used in developing photographic prints, such as silver, iodine, chlorine, and bromine were likely part of her life years before she entered a chemistry lab.

Ball was born in Seattle on July 24, 1892. Her family moved to Hawaii in 1903 hoping that the salubrious weather would alleviate her grandfather’s arthritis. Her family moved back to Seattle in 1905, following her grandfather’s death. She earned two bachelor’s degrees in Pharmaceutical Chemistry and the Science of Pharmacy in 1912 and 1914, respectively. She then decided to pursue a master’s degree at the College of Hawaii, now called the University of Hawaii, and eventually became the first female and first African-American chemistry professor at the College.

Ball became an expert in extracting active ingredients from plants, and caught the attention of Harry T. Hollmann, medical director of the Kahili Leprosy Hospital. He had been trying to treat leprosy patients but hadn’t been making much progress. In a pre-antibiotic world, there was no clear cure for leprosy, although a potential candidate had been known for years. Chaulmoogra had been used to alleviate skin diseases, including leprosy, in India and China for centuries. Eventually, in the 19th Century, Western doctors started experimenting with Chaulmoogra oil to see if it could be used to treat leprosy. But success had been limited. Ingestion had proven to be ineffective and injecting the oil had proven disastrous – the viscous oil clumped under the skin to form blisters, due to which the patient’s skin looked as though it “had been replaced by bubble wrap.” What doctors needed was a form of Chaulmoogra oil that could be absorbed by the body.

Enter Alice Ball, the 23-year-old chemist whose master’s thesis was on the extraction of the active ingredient from a root called the Ava root. In less than a year, Ball devised a way to create a water-soluble injectable form of Chaulmoogra oil.

Ball died shortly thereafter, on December 31, 1916, at the age of 24. It is unclear why she died, although it is possible that she could have gotten chlorine poisoning while teaching in the lab.

Ball did not live to see 84 patients in the Hospital get cured because of the extraction method she had developed. She was also not given due credit for her discovery, as Arthur Dean, president of the College of Hawaii, published Ball’s extraction technique as his own. In was only in 1922 that she got credit for her work, when Hollmann, the surgeon who had initially encouraged her to develop the drug, wrote about the extraction process and called it “The Ball Method.” The injectable form of Chaulmoogra oil became the principal method of treating leprosy until the 1940s. In 2000, then Hawaii Lieutenant Governor Mazie Horono declared February 29 Alice Ball Day.

Barbara McClintock: Discoverer of Transposons

From the time Barbara McClintock was a young girl, it was clear that she was not going to grow up to become a conventional woman. She preferred sports over dolls, and her mother even made her bloomers so that she would be able to play all the sports she wanted “unhindered by dresses.” As her desire to pursue higher education grew, however, her mother’s support of her idiosyncrasies became less enthusiastic. Worried that an academic daughter would be unmarriageable, she was reluctant to allow McClintock to go to college. Her father interfered, however, and McClintock went off to Cornell to pursue a degree in Agriculture.

By the time she graduated, McClintock became an expert at preparing cells for the microscope. She began studying maize and became so familiar with maize chromosomes that she noticed that certain sections of the chromosome broke off and reattached to different chromosomes and that this corresponded with changes in the coloration of the maize. McClintock called these regions controlling elements (they are now called transposons). This discovery greatly expanded what scientists believed that genes could do. Previously genes were thought to be stationary – like, as the popular analogy goes, beads on a string. McClintock developed a strong reputation in the scientific community and was elected president of the Genetics Society of America in 1945, becoming the first woman to serve in the position.

However, what McClintock really wanted to study was how genetic expression was regulated. It was a question that had plagued scientists for decades: how could neurons and skin cells can look so different despite having the same genetic code? McClintock hypothesized that if a transposon landed near a gene, it would turn off its expression, and turn it on when it left. She presented this theory at a prominent symposium in 1951, but her theory – lacking data to back it up – baffled scientists. McClintock withdrew from the scientific limelight after the symposium and didn’t publish her research after 1953. In 1983, Evelyn Keller published a popular biography of McClintock that brought McClintock back into the public consciousness. McClintock was awarded the Nobel Prize in Physiology or Medicine the same year – the first and only woman to receive an unshared Nobel Prize in the category. However, despite the honor, she never succeeded in proving the regulatory functions of transposons, and indeed, subsequent research showed that it is proteins such as transcription factors, promotors, enhancers, and repressors that control gene expression.

Tu Youyou: A cure for malaria

Tu Youyou was born in 1930 to a family that greatly valued education. At university, she trained under a phytochemist who taught her how to extract active ingredients from plants using appropriate solvents. After graduating, Youyou was recruited to the Institute of Materia Medica, Academy of Traditional Chinese Medicine. Her interest in traditional medicine had deep roots. Growing up, she had seen folk recipes being used to treat a variety of diseases and had seen that some of them were quite effective. The Institute of Chinese Materia Medica provided a unique environment for the combination of Traditional Chinese Medicine and Western medicine. It was an institution where historians, who poured over ancient recipes, and chemists and medical doctors, who had modern tools at their disposal, worked side by side.

It was under these conditions that in 1967, Youyou was tasked with developing a drug to treat chloroquine-resistant malaria. Many Chinese and American soldiers were dying due to malaria in Vietnam – and both the United States and China launched campaigns to develop a treatment, and Youyou was recruited to the Chinese campaign.

Youyou’s team collected over 2000 recipes based on over 600 herbs. One of the most promising candidates was Qinghao, the Chinese name for six herbs falling under the genus Artemisia. Handbooks detailing traditional recipes were helpful in refining their techniques of extraction. One recipe, for example, made Youyou’s team attempt a cold extraction instead of performing extractions at boiling temperatures, leading to better results. Youyou extracted the active ingredient from Artemisia annua and it proved to be effective against rodent malarias. In the absence of robust protocols on how to conduction clinical trials in China in the 1960s and 1970s Youyou and her team volunteered inject themselves to ensure that the active ingredient wasn’t toxic. The team then used the drug to treat 21 malaria patients and saw that their fever disappeared. Their drug was 100 percent effective.

Youyou was awarded the Lasker DeBakey Clinical Medical Research Award in 2011 and the Nobel Prize in Physiology or Medicine in 2014 for her work, which, the presenter of the Lasker award described as “arguably the most important pharmaceutical intervention in the last half-century.”

Check out our blog honoring five of Emory’s female inventors and their work here.

Sources:

Nettie Stevens

Alice Ball

Barbara McClintock

  • “Barbara McClintock and the discovery of jumping gene” by Sandeep Ravindran: https://www.pnas.org/content/109/50/20198

  • “’The Real Point is Control’: The Reception of Barbara McClintock’s Controlling Elements” by Nathaniel Comfort: https://www.jstor.org/stable/4331511?seq=1

  • The Tangled Field by Nathaniel Comfort

  • The Violinist’s Thumb: And Other Lost Tales of Love, War, and Genus, as Written by Our Genetic Code by Sam Kean1

Tu Youyou

Treating Anxiety Disorders: Balancing the Real World and the Virtual World

Barbara Olasov Rothbaum, PhD, is the Associate Vice Chair of Clinical Research in Emory School of Medicine’s Department of Psychiatry, a professor in the Department of Psychiatry and Behavioral Science, and director of Emory’s Veterans Program and Emory’s Trauma & Anxiety Recovery Program. Dr. Rothbaum specializes in treatment of anxiety disorders, with a focus on Post-Traumatic Stress Disorder (PTSD). With over 200 scientific publications, Rothbaum has changed the field of PTSD and was a forerunner in the use of virtual reality in treatment of anxiety disorders.

What initially drew you to the field of psychiatry?

I went to UNC-Chapel Hill as an undergrad. I actually went as a math major and that didn’t last long; My freshman year I decided to take a freshman seminar course, which meant there were only fifteen students, on how to design an experiment. It was a psychology course and I had no interest in psychology going in, but it sounded interesting. The course had the kind of teacher you always hope to have, or hope your kids have; the research bug bit me and I loved it. I kept taking more psychology classes and then got involved in research.

Who has influenced you the most in your career and why?

Barbara Rothbaum

Barbara Rothbaum

I learn every day. I learn every day from somebody, from every patient I see. When I think of real turning points; I think of my first professor my freshman year. He changed everything, I gave up all my math courses and went into psychology. When I was an undergraduate, I worked in a fetal alcohol lab under Carrie Randall, PhD, a professor at the Medical University of South Carolina, for a summer. I learned methodological control and precision from her. I also learned that I wanted to work with people after working with animals in Carrie’s lab. Working here at Emory with Michael Davis, PhD, Yerkes Researcher and Robert W. Woodruff Professor of Psychiatry, I started to get into translational research, asking questions of animals and then translating to humans and translating back to animals.

What was the process of integrating virtual reality and anxiety disorder work like?

In 1993, Larry Hodges, PhD, an Associate Professor in the College of Computing at Georgia Tech, contacted me about an Emory-Georgia Tech seed-grant program. Larry specialized in virtual reality and he found out that I was an exposure therapist, meaning that I help people confront their fears in a therapeutic manner. We originally wanted to do the research on fear of public speaking, but in the 1990s virtual reality was clunky. Virtual reality at the time worked more in angles, and people move in arcs. This made it difficult to do public speaking, so we decided to do fear of heights because of the angles and you can easily represent height in virtual reality. Our line at the time was, we “weren’t sure if we were on the cutting edge or the lunatic fringe.”

Could you describe the development process for the first virtual reality treatment incorporating computer scientists and clinical psychology?

Virtual Reality Therapy

Virtual Reality Therapy

I would go to Georgia Tech and I would explain exposure therapy to Larry’s brilliant computer science graduate students to help them understand why people get anxious. For example, we were working on the virtual airplane, there was just way too much room. About half the people who fear flying have a claustrophobia-focused fear that induces panic. Part of the trigger is feeling closed in so you need to remove the feeling of roominess. I would work with the programmers to help them understand the fear cues so they could go back and create them.

Your work has been brought to the marketplace through an Emory start-up Virtually Better – what was that experience like?

The first study was published in 1995, and the response was really amazing. Emory and Georgia Tech thought that there might be a marketable product, so they took us [as inventors] by the hand and drove us to a lawyer to incorporate, and that was Virtually Better. As soon as we incorporated, I received a letter saying that I had a conflict of interest since I was doing research in that area. That freaked me out, and I didn’t understand conflicts completely at the time. I ended up serving on the School of Medicine’s Conflict of Interest Committee for six years. It did limit my research for a while. Now we’ve learned how to manage conflicts; as a result I am able to do more research with virtual reality.

What types of challenges are there for the utilization and growth of virtual reality in psychiatry?

At Virtually Better, we often looked more like an academic department rather than a company trying to make money. This allowed us to get numerous grants, which supported more R&D. Every product we released had good data on efficacy. What scares me now is that people can be working on virtual reality in their garages. We have always had the input from clinical psychologists and computer scientists, we were cutting edge in both fields and releasing what we knew was a good product that a person can benefit from therapeutically. I worry now about quality control and efficacy.

Do you think virtual reality will be a game-changer in Post-Traumatic Stress Disorder (PTSD) treatment?

Well nothing works for everyone. One of the most important things we can have is alternatives and choices. Research has shown that if a patient with PTSD can choose their course of treatment they are more likely to respond positively. With this generation of veterans, which is a video generation, they tend to like virtual reality. It feels a little bit less like therapy to them and feels more “techie.” There was a study done with active duty military populations, that showed that people who feel less comfortable going to therapy would try virtual reality therapy.

What has been the personal satisfaction for you in seeing the progression in PTSD research and treatment?

It has been satisfying and challenging. When I started working in PTSD, there were no indicated treatments, it was just a diagnosis. Psychologists were extrapolating from other treatments for other anxiety disorders. It’s really nice to see that evidence-based treatments for PTSD exist now, but what’s still challenging is that none of them work for everyone. Also, I think some of it is the nature of the beast [with PTSD]. People with PTSD are avoidant; they don’t want to talk about it or go in for treatment. We need to not only develop effective treatments, but also acceptable treatments.

Many who work with PTSD, and other psychological disorders, experience burnout; how do you avoid burnout or compassion fatigue?

I exercise; I do yoga, I ride my bike. We talk about experiences at work in a group setting with supervision as part of the Emory Veterans program. There are some cases that we are talking about that bring tears to our eyes. It’s important that we are able to support each other, it’s not something you can go home and talk about over the dinner table. We hear the worst of the worst. So it’s about work-life balance.

What advice would you give to your younger self?

Problems and roadblocks used to really upset me. I now have the attitude that problems will occur daily, some large, some more manageable, and my job is to navigate them, so I can approach them with more equanimity, wisdom and creativity. I have also had to learn to not take things so personally, for example not receiving a grant or a paper rejection, and to bounce back and start working on the next one. I do give myself a little time (not more than a day) to “wallow” (I wouldn’t use that word for anyone else) following big disappointments. We are only human.

To learn more about Virtual Reality Therapy view our success story. To learn more about Virtually Better go to their website.

Emory Female Inventors

Emory University is home to many brilliant female inventors, whom have contributed ground breaking research and innovation to the society at large. From new treatment methods to life threatening diseases to new accessible techniques of health education, Emory women help shape the world we live in today. March is Women’s History Month and we will be highlighting historical female inventors as well as Emory’s historical female figures and inventors through a series of five blog posts. Here five Emory inventor’s. We hope you enjoy.

  • Marcia Holstad: Consistent and regular dosage of antiretroviral medication is an absolute necessity for all HIV positive individuals. Without strict adherence to a daily treatment regimen these individuals risk further illness or spread of the disease. To combat this problem, Marcia Holstad DSN/RN-C/FNP created the LIVE network, a music program used to educate and motivate HIV positive individuals about living with HIV and the importance of regular medication. The network features multiple music genres; all of which contain original content that is not only accessible and enjoyable, but also informative. The initial response to this music program by a focus group of HIV positive patients was extremely positive with many participants asking to share the network with their loved ones. Holstad used this innovative education method to not only help improve HIV treatment, but also to make learning about the disease and its treatment more fun.

  • Lily Yang: Lily, professor of surgery and radiology, and Nancy Panoz, chair of surgery in cancer research, came to Emory with the goal of exploring the use of nanotechnology to fight disease, with a focus on cancer. She is currently conducting groundbreaking research to develop multifunctional tumor-targeting nanoparticles to detect and identify primary and metastic tumors. She hopes to further the use of these particles to deliver therapeutic agents to targeted tumors. Though a final treatment method has yet to be produced, Yang’s work shows great promise in revolutionizing cancer treatment. (Read read more on our website here.)

  • Cecilia Bellcross: Although the general population is acutely aware of the possible genetic heritability of certain strains of breast cancer, the referral process of at risk patients to undergo genetic testing has been historically erratic. Cecilia Bellcross (TITLE) noticed this discrepancy between at risk patients and genetic testing and saw the need for a more efficient screening tool that would suggest whether a woman should consider further genetic counsel regarding susceptibility to heritable breast cancer. Thus, the B-RST screening tool was born. This method asks women 6 basic questions regarding their personal and familial cancer history to identify individuals particularly vulnerable to heritable breast cancer. The results of this screening tool can then recommend whether those individuals should seek further medical council and genetic testing. The B-RST tool was such a success it is used by individuals and medical professionals around the world.

  • Sheila Angeles-Han: Approximately 5 million children in the U.S. suffer from some degree of visual impairment, however many available diagnostic surveys regarding visual ailments are written for adults. Recognizing the need for an age appropriate diagnostic tool, Sheila developed a new survey made up of questions to assess the effect of visual impairment on the quality of life and function in youth. This survey has vastly improved both the accuracy and efficiency of diagnosing and treating impaired vision in children. (Read more on our website here.)

  • Rani Singh: When it comes to metabolic disorders like Urea Cycle disorders or Phenylketonuria, the use of drug or vitamin supplement based treatments is often less successful than the use of a strict dietary regimen. These types of disorders are often negative reactions to intake of certain amino acids or compounds. Therefore, using a structured dietary plan, including restriction and or avoidance of certain foods, many metabolic diseases can have minimally disruptive symptoms. However, active and diligent adherence to medically suggested dietary guidelines is often extremely complex and arduous. Knowing this, Rani, the director of metabolic nutrition program at Emory’s division of medical genetics, developed a pocket-sized food list booklet that contains clear and accessible information on specific metabolic diseases as well as medically recommended dietary restrictions. (Read more on our website here.)

Interviews with two female inventors
Barbara Rothbaum – Treating Anxiety Disorders: Balancing the Real World and the Virtual World
Harriett Robinson – From Academic Researcher to Startup Scientist: Leaving the Lab to Pursue Your Innovation

From Academic Researcher to Startup Scientist: Leaving the Lab to Pursue Your Innovation

Each year OTT helps launch a number of startup companies based around discoveries made by Emory faculty or staff.  In most of those cases the faculty member remains at the university as a researcher or clinician while he or she simultaneously serves in some type of advisory role for the company. In some instances however faculty leave the university environment to strike out into the exciting world of startups. In this piece we talk to former Emory professor Harriet Robinson, PhD, who is now the Chief Science Officer at GeoVax, an Emory startup developing HIV vaccines based on previous work from her lab.

Before you created the HIV vaccine technology, had you ever given much thought to the commercialization of university discoveries?

Yes, I had previously wanted to commercialize a different vaccine technology that I discovered while at another university. At that time it was not possible due to state restrictions that limited the ability of faculty to license their own findings from the university. Those limitations stemmed from legislation created to curb legislators from awarding contracts to themselves or relatives.

What made you decide to follow the technology to a startup company rather than stay in academic research at Emory?

Harriett Robinson, PhD Photo

Harriett Robinson, PhD

At a certain point, the vaccine technology needed expertise that was not present at Emory, for example, manufacturing, formulation, and regulatory expertise. It also needed full-time effort which was not compatible with being a full-time professor.

What has been the biggest challenge in moving out of the academic lab and into industry?

Maintaining funding focused on the commercial development of a product. For HIV vaccines in the developed world, funding is primarily from the NIH. This means that one has to steer a course that meets study section approvals as well as company objectives.

What is the biggest difference (or multiple differences) between an academic lab and an industry lab setting?

The biggest difference is that in industry, one is part of a team that has set out to achieve a goal. If something doesn’t work, the team figures out how to make it work rather than just going on to some other project that is interesting at the moment.

What advice would you give younger faculty interested in technology commercialization?

The small biotech world is very different from the university. Make sure you are really interested in working towards specific products and willing to give up the freedom (and resources) one has in the university to explore multiple different areas of research.

Many Thanks to Dr. Robinson for agreeing to participate! For more information on OTT’s efforts to support faculty entrepreneurship & startups check out our website: http://ott.emory.edu/startups/formation/index.html and http://ott.emory.edu/inventors/education.html. For additional information about GeoVax and their clinical stage HIV vaccine please see their website www.geovax.com.