I have often thought that scientists and musicians have a lot in common. A few young children take pleasure in observing the natural world around them, from stars in the sky to butterflies in the garden. Another few young children are thrilled by their first exposure to music. These are rare talents, and if such children are lucky, their parents and teachers recognize the unusual talent and encourage the child. As a child, I had an affinity for science and music. My mother was wise and made sure that I was exposed to both so that I could choose. I had violin lessons when I was in the fifth and sixth grades. Later, in my teen years, I told her that I liked the sound of an accordion I heard on the radio. A month later, I was the owner of a 120 bass Frontalini accordion and enrolled in accordion lessons at Lazarus department store in Columbus, Ohio.
By that time, I was a high school student in Westerville, Ohio, where my interest in science grew, in large part because I was fortunate to meet three other boys with similar interests, Bob Keller, Jake Elberfeld, and Steve Kahler. We decided to call ourselves the Westerville Science Club. This was spontaneous, by the way. No one told us it would be a good idea to form a club, but if we did not have that shared interest, our lives would have been very lonely. I have vivid memories of the four of us chasing and collecting tigers, zebras, and giants in the fields near Alum Creek (those were the common names of beautiful swallowtail butterflies). In 1955, I exhibited my collection at the science fair in Delaware, Ohio, and came home with a blue ribbon. I think the judges were impressed that a 14-year-old kid knew the Latin names of all his specimens, which I can still recall 70 years later. For instance, the scientific name of the giant swallowtail is Papilio cresphontes.
Figure 1. Tigers and zebras and giants…Oh my!
The fact that science fairs existed was a revelation. It meant that society had an interest in cultivating and encouraging young people with scientific talent. This went far beyond the simple pleasures of four high school kids in the Westerville Science Club who collected butterflies. My parents also realized this, of course. My father was a hydraulics engineer in the aircraft industry and decided to help his son by purchasing an old Zeiss microscope from a local college for $100. I will be forever grateful for the wisdom of his decision because it let me experience science far beyond a high school science club and local science fairs. With a microscope, I could explore another living world that existed all around us: the world of protozoa. It was fascinating to put some dry hay into a glass of water and watch life emerge: paramecia, rotifers, amoebas, vorticella, and many more.
Figure 2. A paramecium and a hungry amoeba. (Credit: Carolina Biological Supply).
This became a passionate interest. I used my father’s Exacta camera to take photos of the protozoa as they swam around in a drop of water on a microscope slide covered by a cover slip. Then, I saw something strange happening when the protozoa populations became dense. They began to form clusters, which turned into rings that expanded toward the edge of the cover slip. I found a way to hold the camera above the microscope that let me take photos of the clusters and rings. I guessed that they might be using up oxygen and releasing CO2 into the center of the cluster, and the rings formed because they were moving away from the acidic anaerobic center toward the edge, where there was more oxygen and less CO2. I didn’t know the word “hypothesis” at the time, but that’s a fancy word for my guess. If the guess was correct, a pH-sensitive dye should change color in the center, so I added phenolphthalein, which was pink in alkaline conditions and clear in acidic conditions. It worked! The centers of the rings changed from pink to clear, and I had the jolt of pure pleasure that comes from discovering something new.
I had heard of the Westinghouse Science Talent Search, a national science fair that invited high school students from all over the country to submit 1,500-word essays about research they had done. I wrote about the dense cultures of motile protozoa that formed clusters and rings and then sent it off and forgot all about it. Several months later, my mother handed me a mysterious telegram that had arrived. It was addressed to me, so we opened it and discovered that I was one of the 40 winners who were invited to spend a week in Washington, DC, competing for cash prizes. The Columbus Dispatch ran a front-page story with my photo. Next day, it felt different when I attended classes at Westerville High School. The local nerd who collected butterflies but wasn’t on the football team had unexpectedly emerged from his anonymous cocoon.
One by one, members of the Westerville Science Club achieved a prize that opened another world to us: a driver’s license! Central Ohio had been flattened by huge glaciers during the last ice age, but Kentucky and West Virginia were untouched. This meant that the underlying limestone deposits were exposed to water that carved vast caves waiting to be explored. This was irresistible to four teenage boys, so we joined the National Speleological Society and bought hard hats with carbide lanterns. Here (Figure 3) is a posed photo of me and my father, taken in 1957 by the photographer for the Columbus Dispatch. I was National Speleological Society member number 3643.
Figure 3. A photo op: my father and I pretending to explore a very tiny cave in central Ohio.
Exploring caves became a serious business for the Westerville Science Club after we joined the Cave Research Foundation (CRF), a group that had permission to map the caves associated with Mammoth Cave in Kentucky. This was the Mount Everest of the speleological world, and between 1958 and 1961, we were members of CRF expeditions as they explored Crystal, Colossal, and Salts caves. One of the CRF goals was to link the caves to Mammoth Cave itself. I had the good fortune to be on two caving trips that discovered links between Colossal and Salts cave and then between Crystal and Salts cave. A few years later, another CRF group finally found a link to Mammoth Cave, making this the longest cave in the world, with 400 miles of mapped passageways! You can read about our adventures in The Longest Cave, a book written by Roger Brucker and Richard Watson.
I have lasting memories of those teenage years. The pleasure of doing research led me to major in chemistry at Duke University, then on to receiving a PhD at the Ohio State University School of Medicine, followed by post-doctoral research at University of California (UC) Berkeley, where I learned to do electron microscopy. In 1967, I became an assistant professor in the zoology department at UC Davis, and then in 1994 I moved my lab and one PhD student to UC Santa Cruz, where I completed the last 30 years of my career and am now emeritus. My Icelandic wife Ólöf Einarsdottír was a professor of chemistry, and I enjoyed watching her progress through her entire academic career as she juggled laboratory research, teaching chemistry to undergraduate students, and being the mother of our two daughters, Ásta and Stella. Ólöf is now emerita and loves singing, and this year her symphonic choir performed at Carnegie Hall in New York City.
The reason I briefly outlined this personal history is to lay a foundation for my impression of the Association for Biological Resource Facilities (ABRF) meeting that I attended last March in Las Vegas. The founders of ABRF must have realized that careers in academic science are unlike any other career. University scientists are paid not just to teach but also to explore the world we live in. Physicists study how universal laws govern the properties of matter and energy, chemists investigate how atoms and molecules react by changing their electronic structure, and biochemists and biophysicists use that knowledge to understand how living organisms incorporate matter and energy to be alive. At the other end of the size scale, astronomers study the origin and evolution of stars and planets, solar systems, galaxies, and the universe itself.
I have often compared the life of a scientist to the life of a prospector in 1849 during the gold rush. Prospectors were given grubstakes by investors to support them as they searched for gold. Scientists are given grants to spend years in their laboratory searching for new knowledge. Prospectors occasionally found the motherload of gold, and scientists supported by grants occasionally discover knowledge that can be immensely valuable, both in terms of human well-being and industrial applications. How are the grant funds spent? That is where academic scientists fit into the goals of ABRF because the funds are shared by small communities of graduate students and post-docs doing research in a professor’s lab. Most of the money is used to support the needs of those young scientists as they make progress through several years of work toward their PhD and publishing their first research paper. Figure 4 is a photo of one of our groups that was involved in developing the fundamental principles of nanopore sequencing at UC Santa Cruz.
Figure 4. The UC Santa Cruz nanopore gang in 2010.
Besides salaries, some of the grant money is used to purchase major equipment items. While I was doing post-doctoral work at UC Berkeley, I learned how to use a Siemens electron microscope that was shared by faculty in the botany department. When I began my first faculty position at UC Davis, I used a shared Hitachi electron microscope in my research. I am now at UC Santa Cruz and have access to instruments that do x-ray diffraction, nuclear magnetic resonance, and mass spectrometry.
These are expensive instruments, but now I want to describe how we developed a less-expensive device that is letting us investigate the base sequences of DNA and RNA one molecule at a time. In June 1989, after giving a talk at the University of Oregon in Eugene, I was driving east to join my family, who were on vacation at a resort in eastern Oregon. The Human Genome Project had just been approved, with a budget of $2.7 billion and a 13-year timeline. As I was driving, I wondered if there might be a simpler, less expensive way to sequence DNA, and I suddenly had an idea. I parked along the side of the road, grabbed a notebook and a red ink pen I happened to have in the car, and made the sketch shown in Figure 5.
Figure 5. The original notebook with a sketch of nanopore sequencing. An applied voltage pulls a single nucleic acid molecule through a nanoscopic pore, and each base causes a base-specific modulation of the ionic current passing through.
Not much happened for another two years because I did not have the resources needed to test the idea or graduate students who wanted to work on it. During my post-doctoral years at UC Berkeley, from 1965 to 1967, I had collaborated with Dan Branton, a young professor in the botany department. He later joined the biology faculty at Harvard, so in 1991, I invited Dan to be a distinguished lecturer at UC Davis. During his visit, we had plenty of time for conversations. During one of them, he told me about an idea he had for sequencing single DNA molecules, and I shared my concept of nanopore sequencing. We tossed the idea back and forth, getting more and more excited, and finally decided to take the next step, which was to apply for a patent through the Harvard office and share with the University of California. Then, Dan discovered that George Church at Harvard had a similar idea! Dan and I met with George over lunch at the Harvard Faculty Club and decided that we should share inventorship. This was an easy decision because we had no evidence that either of our ideas would work.
Now it was time to get serious and test the idea. In the early 1990s, I began to hear about a toxic protein called alpha hemolysin. It was secreted by Staphylococcus aureous and received its name because it would punch tiny holes in red cell membranes, causing them to become leaky to sodium and potassium ions. As a result, the red cells would swell, and their hemoglobin would leak out, a process called hemolysis. John Kasianowicz at the National Institute for Science and Technology had established a method to insert a single hemolysin channel into a lipid bilayer membrane. By applying an electrical voltage across the membrane, he could measure the ionic current passing through the channel. At the time, he was collaborating with Hagan Bayley at the Worcester Foundation for Experimental Biology with the goal of using the hemolysin channel as a way to detect metals like zinc in the environment.
The hemolysin channel conducted much more ionic current than other channels, which suggested that it might be large enough to accommodate a strand of nucleic acid passing through. I wrote to Kasianowicz, asking if I could visit and bring along two different kinds of RNA to see if they could be detected by the hemolysin channel. John agreed, so I showed up at his lab in Gaithersburg, Maryland on December 12, 1993, with vials of RNA homopolymers called polyuridylic acid and polyadenylic acid. I watched as John established a lipid bilayer membrane of phosphatidylcholine across a tiny hole in a supporting Teflon sheet immersed in 1.0 M potassium chloride solution. He then added hemolysin to the solution, bathing one side of the membrane, and turned on a small electrical voltage. As expected, the ionic current remained at 0 because the membrane was impermeable to ions. We waited, several minutes passed, and suddenly the ionic current increased dramatically when the hemolysin assembled into a single heptameric channel that allowed a current of potassium and chloride ions to flow through.
Then, we performed the experiment I had traveled from California to do. John turned the voltage off, and we added a small amount of polyadenylic acid to the solution on one side of the lipid bilayer. John turned the voltage up to 10 mV, and the steady current flowing through the channel was registered by a pen drawing a line on a chart recorder. John continued to increase the voltage 10 mV at a time, and the line showed an increased current each time, as expected. But when he reached 80 mV, something new happened. We began to see occasional downward deflections lasting a few milliseconds. At 100 mV, there were many more, on average one per second, and at 120 mV, the pen was making a chattering noise as it flicked up and down 10 times per second. We realized that each downward deflection was caused by a single molecule of RNA zipping through the channel and producing a transient blockade of the ionic current. The experiment had worked, opening the door to the possibility that nanopore sequencing was feasible. We published our first paper three years later in December 1996.
The results described in that paper were the centerpiece of a grant proposal I wrote that was funded by the National Institutes of Health (NIH). That was the beginning of the basic research that laid a foundation for nanopore sequencing performed at UC Santa Cruz. Dan Branton also began to write funded grant proposals, several of which we shared. Now I could support the salary of a research associate, so I invited Mark Akeson to join the project. Mark had been a post-doctoral researcher in my lab at UC Davis but afterwards became a scientist at NIH as the next step in his career. He had read our first paper and was skeptical but decided to take a chance, so he and his family moved to Santa Cruz, purchasing a home in Bonny Doon near where my family was living.
If Mark had decided to stay at NIH, I am not sure that nanopore sequencing would have ever become a reality. He is an immensely talented scientist with the rare ability to focus intensely on a research problem. In 1997, after Mark had settled into his new position, Dan and Lana Branton spent a six month sabbatical in Santa Cruz. We improved the support for the lipid bilayer membrane and hemolysin channel, and in 1999, Mark published his first paper in which we demonstrated that hemolysin could tell the difference between polyadenylic and cytidylic acid polymers translocating through the channel. This was an important observation. If we could not tell the difference, it would mean that distinguishing between bases in a DNA or RNA strand might not be possible. We also invented a new word used for the first time in this paper. We referred to hemolysin as a nanopore, defined as a nanoscopic pore in a membrane that could accommodate passage of a long anionic polymer like a nucleic acid.
Because other researchers could not believe that it would be possible to sequence a single nucleic acid molecule passing through a nanopore, we had the field to ourselves for a few years. We continued publishing papers with funding from the NIH, National Science Foundation, Defense Advanced Research Projects Agency, and even Agilent, the instrument company. Then, a new funding source emerged when the National Human Genome Research Institute was opened as a new division within NIH. Jeff Schloss became the program director of the $1000 Human Genome project, which made grants available to academic scientists as well as businesses like Illumina, 454 Life Sciences, and PacBio.
Oxford Nanopore Technologies (ONT) was founded as a British startup company in 2005, and in 2007, Gordon Sanghera and Spike Willcocks visited us at UC Santa Cruz and Dan Branton at Harvard. They had decided that nanopore sequencing might actually be feasible, so they licensed the patents we had developed. In hindsight, this was pretty risky because there were some unresolved problems to be overcome. For instance, ONT needed to find a way to have thousands of individually addressable pores in a chip and not just one that we used. They also had to develop a supporting membrane that could survive shipping. A method to slow translocation of a DNA strand from 500,000 bases per second to 500 bases per second was essential, and Mark Akeson led a team of graduate students in our lab who showed how this could be achieved with motor proteins. ONT also needed software that could do base calling, in which the electrical modulation caused by each base passing through the pore could be identified and added to the sequence. This was far beyond what a small team of academic scientists could achieve, but seven years later, the first commercial device called a MinION arrived in my laboratory, purchased from ONT for $1,000. Figure 6 shows Mark Akeson and me demonstrating what it looks like to do nanopore sequencing with a MinION and a laptop. We were very happy!
Figure 6. Mark, myself, and our first MinION.
This brings me to the main point that I want to make. Without realizing it, my entire academic career ran in parallel with the goals of ABRF. I was able to join academic groups that were equivalent to the shared research resources of ABRF—but with one difference. Our shared research resources were private, pretty much limited to small groups of faculty members who had done the work of writing grants and applying for funds to purchase the equipment. The users pay a modest recharge to underwrite the salaries of expert technical staff who maintain the instruments and demonstrate how to use them. I think this is a time when ABRF has an opportunity to step into a national leadership role. ABRF and its policies and methods for sharing research resources can expand access to scientific equipment and facilities. ABRF can also bring together young and senior scientists not just within departments but also scientific communities. Astronomers and particle physicists learned how to do this years ago because hundreds of researchers are using equipment costing not millions but billions of dollars. One example is the James Webb telescope parked at the Lagrange point L2 between the Earth and the sun and another is the CERN laboratory in Europe where the Higgs boson was discovered. Biologists also had a taste of working in a “big science” community when the Human Genome Project began in the year 1991 with 20 research groups doing the work. Ten years later, the human genome was posted online by Jim Kent and David Haussler, who are associated with my department at UC Santa Cruz.
To sum up, relatively few scientists have heard of ABRF and how it is promoting an expanded vision of shared resources. Those resources are already bought and paid for in American universities. ABRF can show how they can be organized to serve larger scientific communities nationwide.
EDITOR’S NOTE
David Deamer, PhD, research professor of biomolecular engineering at the UC Santa Cruz, accepted the ABRF Award in recognition of his outstanding contributions to biomolecular technologies at the ABRF 2025 Annual Meeting in Las Vegas, March 23 to 26. In 1989, Deamer proposed using a nanoscopic pore embedded in a lipid bilayer membrane to sequence DNA molecules. Working with Daniel Branton (Harvard University), Deamer helped draft a patent application in 1991 for single-molecule analysis via nanopores. The patent, issued in 1998, laid the groundwork for the technology that is now an indispensable tool in genomics as well as for Oxford Nanopore Technology, founded in the United Kingdom in 2005. Deamer was elected to the National Academy of Inventors in 2023. In the same year, Deamer, Branton, and Akeson were recipients of the Golden Goose Award at a ceremony in Washington, DC. This award recognizes research that was initially viewed with skepticism but ultimately led to significant societal impact.
Although Oxford Nanopore sequencing devices now fit in the palm of your hand and are used everywhere from university labs to the International Space Station, Deamer remains focused on the question that first ignited his career: How did life begin? Deamer’s ongoing pursuit of life’s fundamental questions exemplifies the transformative power of bold ideas and daring entrepreneurialism. His research underscores how the fusion of innovative science and a willingness to take risks can propel us into uncharted territories of knowledge, from the formation of primitive RNA strands in boiling puddles to the potential detection of life on Mars.
As is evidenced by his career, Deamer is an innovator, collaborator, and team scientist. In this publication, Deamer recognizes ABRF’s prominent national role and encourages ABRF to take a leading role in promoting policies and methods for shared research resources, educating researchers and policymakers about the vital role of cores in the research ecosystem, and bringing together scientists to advance collaborative science worldwide.