Barry Stoddard, PhD
Barry Stoddard is a structural biologist. His research focuses on revealing the three-dimensional structures of proteins and modifying them to help treat or cure diseases like cancer, cystic fibrosis, or HIV. Dr. Stoddard grew up in rural Northern Idaho, studied biophysical chemistry, and launched protein crystallization experiments into space aboard a USSR space station (he wrote a book about that experience!). He is a Professor in the Division of Basic Sciences at Fred Hutchinson Cancer Center, an Affiliate Professor in the Department of Biochemistry at the University of Washington, and a Principal Investigator for the National Cancer Institute’s Interdisciplinary Training Program in Cancer.
Faculty Directory
Lab Website
Twitter
What is Structural Biology?
Structural biology is a specialized field of study focused on how biological molecules are built and how their shapes determine how they function. Dr. Stoddard described the job of a structural biologist as “an investigator who attempts to determine how biological molecules (DNA, RNA, proteins) and larger systems made up of those molecules (all the way up to entire living cells) carry out their functions, by determining the three-dimensional, atom-by-atom architecture of those molecules and systems.” He explained that “the basic idea is that if I want to know how something works, a great starting point is to see what it looks like, in as much detail and as precisely as I can.”
Dr. Stoddard provided an analogy for understanding the types of questions that structural biologists investigate:
“Imagine, for example, that I told you a device existed that could transfer the power of an engine to the rotation of a car's wheels on the road. That's well and good, but if I showed you exactly how a car's differential (the device that turns the rotation of a car's drive shaft into the rotation of a car's axles and tires) is constructed and what it looks like, you'd suddenly go from knowing 'what' that device does, to having a really good idea of 'how' it does it. The same principle applies to a biological molecule. I could tell you that a protein called 'Factor VIII' helps blood to clot when you cut yourself, but if I show you what that protein looks like (and I can...we solved its structure years ago), I can easily explain to you how it goes about accomplishing that task.”
“Nothing is more exciting to me than to predict how molecules are going to behave, based on what I think I know about them, and then having that prediction actually work out correctly!”
— Dr. Barry Stoddard
Dr. Barry Stoddard's Story
Childhood and Adolescence
Dr. Stoddard grew up in rural Northern Idaho, outside of the city of Sandpoint, an area known for its forested mountains, ski resorts, and the state’s largest lake. His mother was an elementary school teacher and his father worked in the forest products industry.
Dr. Stoddard’s parents raised him to have a strong work ethic. Reflecting on his childhood, Dr. Stoddard shared, “I spent all my time either working hard in school (an expectation of my parents that was absolutely non-negotiable) or working hard outside of school (any money I ever hoped to have in my pocket came solely from hustling for jobs), and playing hard otherwise (I spent a LOT of days and hours in the hills around our home and up on the ski slopes back when that activity was dirt cheap).”
Though he didn’t have a clear plan of what he wanted to do for a career, Dr. Stoddard knew that he would go to college. He reflected that he was “generically interested in science and in biology and chemistry from middle school onwards, and in particular after taking sophomore chemistry from a particularly outstanding high school teacher.” Dr. Stoddard had some amazing teachers in high school who ignited and sustained his interest in learning. This included his chemistry teacher Mr. Jim Bauer, his trigonometry and physics teacher Mr. David Parker, and all of his English teachers. As a teenager with a thirst for learning, Dr. Stoddard recognized that he was good at being a student, and he reflected, “really, I'm still a student to this very day.”
College Years
His mother, father, and grandmother are all graduates of Oregon State University – go Beavers! However, Dr. Stoddard chose a different route. Heading to the small town of Walla Walla, Washington, Dr. Stoddard started school at Whitman College with “a vague plan” to later apply to medical school to become a doctor. Though he majored in Chemistry/Biology, Dr. Stoddard greatly values the liberal arts education he received at Whitman. He reflected, “what this school really provided me was a LOT of opportunities to write, and write, and write some more. That, just as much (if not more) than the really good education I received in chemistry and biology, set me on a path to success at the PhD level.” When his senior year rolled around, Dr. Stoddard found himself applying for graduate school instead of medical school. He explained, “Once I was admitted to MIT, my course was set.”
Graduate School and Beyond
Next, Dr. Stoddard moved across the country to the east coast to attend graduate school at MIT in Cambridge, Massachusetts where he studied Biophysical Chemistry. After graduating with his PhD, Dr. Stoddard moved back to the west coast for a two-year position as a postdoctoral researcher at the University of California, in Berkeley, California.
During graduate school and his postdoctoral training, Dr. Stoddard was mentored by biochemists Dr. Greg Petsko and Dr. Dan Koshland. Dr. Stoddard described them both as “highly imaginative and creative scientists with a fearless attitude towards research and learning, and with great compassion and supportive personalities towards their trainees.” He noted, “They both provided me and my adjacent PhD students and postdocs with enormous freedom to pursue their own interests and to be creative themselves, while always being available for guidance and boundaries as needed.” Today, Dr. Stoddard serves as a mentor to trainees. He reflected that Drs. Petsko and Koshland “were both models for how I've tried to conduct myself as a research mentor ever since.”
Educational Pathway
- Undergraduate: B.S., Chemistry/Biology, Whitman College, Walla Walla, WA
- Doctorate: Ph.D., Biophysical Chemistry, Massachusetts Institute of Technology, Cambridge, MA
- Postdoctoral Training: Postdoctoral researcher, University of California, Berkeley, CA
Protein Crystallization Experiments in Space
Dr. Stoddard’s adventures in science have extended all the way to space. He shared, “Science has provided me many opportunities to travel the world and to meet people and see sites and events that I never would have imagined when I was in school.” While in graduate school at MIT, Dr. Stoddard and fellow students Dr. Roland Strong (now a biophysicist at Fred Hutch) and Dr. Greg Farber were recruited for a special project by Payload Systems, Inc., a small Massachusetts-based company. The company was dedicated to facilitating research in space using NASA space shuttles, including a focus on exploring if the microgravity environment experienced by orbiting spacecraft could ease the tricky process of transforming proteins into protein crystals. Crystallization of proteins can help scientists understand a protein’s three-dimensional structure, and therefore provide insights into how it functions.
However, after the NASA Space Shuttle program was grounded for several years following the tragic accident involving the Challenger shuttle in 1986, the company lost its ability to send experiments to space. To solve this problem, Payload Systems turned to a new collaboration with the Soviet space program and quietly sought out the work of MIT graduate students researching protein crystallography. In an event that attracted global attention, American graduate students Stoddard, Strong, Farber and their team launched protein crystallography experiments, the first ever American cargo to travel aboard a Soviet spacecraft, to the Soviet space station Mir. Stoddard, Strong and Farber traveled to the Baikonur Cosmodrome in present-day Kazakhstan for the launch on a winter morning in December 1989. Ultimately, a total of three of their experiments would reach Mir between 1989 and 1993. This was a critical time in history – when the Cold War came to an end, communism crumbled, the Soviet Union split apart into fifteen independent nations, and Russia-US diplomatic relations improved (though only temporarily).
Amidst this dramatic backdrop, unfortunately the results of their protein crystallography experiments in microgravity were underwhelming, especially given the cost of sending them to space. However, microgravity crystallization experiments have continued aboard the International Space Station, with a continued hope they will offer new insights into treating or curing human diseases. Drs. Stoddard and Strong went onto careers as researchers at Fred Hutchinson Cancer Center and Dr. Farber became the director of the Office of Technology Development and Coordination at the National Institute of Mental Health.
Dr. Stoddard wrote a book about this incredible experience: “Baikonur Man: Space, Science, American Ambition and Soviet Chaos at the Cold War’s End” (March 2023). He shared, “Of all the adventures in science that I've ever had, that project and our travels to Russia and Kazakhstan at the final 'crescendo' of the cold war and the corresponding collapse of the Soviet Union was by far the most memorable and crazy (hence the book!).”
Read more about Drs. Stoddard and Strong’s experience sending experiments aboard the Mir Space Station in the article “‘Outrageous experience’: Researchers recall pioneering experiments on Soviet space station.”
Work Hard, Play Hard, and Eat Almost Anything
Outside of work, Dr. Stoddard enjoys reading, traveling, and going to the theater and music performances, as well as skiing, golfing, and diving. He will eat virtually anything (except olives and lentils, both of which he admits hating). He explained, “I'm willing to try anything interesting at least once and have yet to regret doing so.”
A Day in the Life
A typical day at work for Dr. Stoddard includes a variety of tasks, many of which revolve around writing. Dr. Stoddard summed it up like this: “If I had to describe what I have to be good at in my job, I would say a little bit of all fields of science (biology, chemistry, physics), a whole lot of writing (fast, efficient and clear), and plenty of inter-personal communication and empathy.”
Writing is an important everyday activity in his professional life. Dr. Stoddard explained, “I will start and then end the day handling my duties [as senior editor of the scientific journal Nucleic Acids Research], for which I'll examine new papers that have been submitted, assign them to various editors who work under me, and take care of any tasks for those papers that I'm personally handling and putting through peer review.” He also “almost always spend[s] time working on writing text for [journal] manuscripts that describe our work, information needed for our funding agencies, and communications with our many collaborators.”
As a researcher, much of his energy is also focused on directing the scientific work going on in his lab. He shared, “I'll take time to talk to staff within my lab, one-by-one, and hear about their latest experimental results, ideas and thoughts.” On a good day, he said, “I'll get to spend a fair amount of time planning experiments, both for folks in my lab and (when it works out) for myself.”
Scientific research is challenging and fraught with productive failures. Dr. Stoddard reflected, “The single biggest challenge (other than keeping the lab funded, which is a concern every single day) is that in research, about 9 out of 10 things you try are going to fail.” He continued, “However, every such 'failure' is really just a stepping-stone to figuring out what you don't understand about the molecule or the system that you're studying, which hopefully eventually guides you to the 'answer'.” Working in an environment with so much uncertainty can be difficult. Dr. Stoddard shared, “A really big challenge for any researcher, including me, is the ability to embrace working in a field where you spend most of your time wondering why most of what you're trying to do isn't working, then trouble-shooting and changing your ideas as a result.”
Protein modeling and engineering
The scientists who work in the Stoddard lab are focused on understanding, modeling, and engineering proteins to treat and cure human disease and solve other problems. Dr. Stoddard explained, “We are involved in designing, from scratch, entirely new protein molecules that fold into desired shapes and that can be used as tools and reagents for biotechnology and various medical and industrial applications.” He continued, “This project involves not only understanding how proteins fold into various shapes and structures, but then using that knowledge and understanding to predict and design new types of proteins, and then being able to check that they indeed behave as designed (by making the proteins and then seeing what they look like).”
Dr. Stoddard explained that the purpose of this research is to create molecules that might be useful across many contexts, including:
- Stimulating the growth of anti-tumor T-cells in culture, for use in cancer immunotherapy applications.
- Destroying bacterial biofilms that are a major problem both in medical applications and in industry.
- Breaking down environmental plastics (such as polyethylene) for improved bioremediation of contaminated water sources.
- Creating new vaccine platforms.
The importance of high school chemistry coursework
Dr. Stoddard thinks it is important that high school students know that the concepts they learn in a high school chemistry class lay the foundation for the type of scientific understandings that the members of his lab are seeking. He shared, “It's worth noting that being able to create new proteins with new abilities such as these requires that we understand the chemistry of proteins at a really deep level.” Continuing, he explained, “While that may sound intimidating, because proteins and other biological molecules are so large (consisting of thousands to hundreds of thousands of atoms), the happy news is that the same rules that students learn in high school about why individual atoms and small molecules behave as they do, are exactly the same rules that govern the behavior and structure of large biological molecules.” Therefore, “what a student learns in sophomore chemistry applies to a PhD student learning about and working with our molecules,” he stated.
Tools of the Trade
Structural biologists like Dr. Stoddard primarily use three techniques in their efforts to determine the three-dimensional architecture of biological molecules or larger assemblages of those molecules:
- X-ray crystallography, a special type of microscopy.
- Electron microscopy, which is often called CryoEM. This is a different type of microscopy in which samples are cooled to extremely low temperatures.
- Computational structure predictions, largely using a program called AlphaFold, which is a new AI algorithm. AlphaFold uses AI to determine a protein’s structure from its amino acid chain to solve a particularly tricky scientific challenge known as the protein-folding problem.
Video: Electron Microscope at Fred Hutch
This time lapse video shows the complicated setup process of the Glacios electron microscope at Fred Hutchinson Cancer Center, and all of the people across different jobs who were involved in the task. The 200 kV ThermoFisher Glacios X-FEG electron microscope is accessible to scientists at Fred Hutch through the Electron Microscopy & CryoEM Core.
Video: AlphaFold Protein Folding
This video from DeepMind explains why it is important to identify the 3D structure of proteins , why it is so difficult to solve the puzzle of how proteins fold, and how AI may help.
Video: Basic Sciences Research Can Save Lives
Watch this short video to hear Dr. Stoddard talk about his work, and how the application of basic science research like his can save human lives, such as for people facing a cancer diagnosis. Dr. Stoddard’s mother passed away from glioblastoma (a type of brain cancer) in 1997 at age 59. In a full circle moment, one of Dr. Stoddard’s gene editing projects that produced a modified protein with anti-tumor properties was taken up by other scientists and explored as a promising targeted cancer therapy for aggressive glioblastoma. This is an exciting example of how basic science research can be applied to clinical purposes to treat human disease.
Advice for Students
Dr. Stoddard offered two pieces of advice for high school students interested in pursuing a career in scientific research in the biomedical field. First, he advises that students “study and be interested in as many things as you can...don't be forced into hyper-focusing or specializing one moment sooner than you have to.” Reflecting on his liberal arts education, Dr. Stoddard believes that “History and the fine arts are every bit as important and useful to you now as science; learning and thinking are universal.”
Secondly, Dr. Stoddard is a huge advocate for developing skills to write well and efficiently. As a high school student in Sandpoint, Idaho, he took every possible class he could in science, math, and writing. He reflected that his high school English classes “set me on the road to being able to write well, which is the one thing that most people don't realize is absolutely critical to being a successful scientist.” Dr. Stoddard emphasized that in his job as a structural biologist and researcher, he writes all of the time. He explained, “Honestly, I see more young trainees struggle and flounder as a result of not writing easily and efficiently than I do as a result of not mastering the basics of a scientific discipline.” Dr. Stoddard believes that writing is “a HUGE part of any and all professions, and certainly of any form of science” and that “those who struggle with it usually hit a brick wall (or ceiling, if you prefer) of how far they can advance in the profession of scientific research.”
"Research is an intense and highly social enterprise that is supposed to be both challenging and fun, and that forces us all to deal with daily failure that hopefully points us towards eventual success. Helping early-stage students and trainees learn how to be effective researchers is the most enjoyable part of the job."
— Dr. Barry Stoddard
U.S. Wage Information
According to the 2023 U.S. Bureau of Labor Statistics’ Occupational Employment and Wage Statistics, the average wage for biological scientists in the U.S. is $99,060.
Additional Resources
Credit: Thank you to Dr. Barry Stoddard for graciously sharing his story. Career profile written by Dr. Kristen Clapper Bergsman.