Dr. James Crowe

"Cause I know there's a God up in heaven / who must love rock and roll"

 -Gregg Allman, "Ocean Awash the Gunwale", 1988

Talking with Dr. James Crowe, MD, I'm immediately reminded of my favorite teacher from elementary school, who was, coincidentally, the voice that led me in the direction of science in the first place. Suffice it to say, Dr. Crowe (pictured above, and during his TEDx Nashville talk, "Unraveling the Mystery of Immunity") is exactly the kind of communicator that science needs - he also happens to be a world-renowned microbiologist and infectious disease expert. The projects he and his colleagues have set their sights on could yield century-defining medical innovations (which you'll read about below). Yet, his humble tone belies that paradigm-shifting ambition.  

Here, Dr. Crowe reflects on his medical missionary work in East and West Africa, the

Human Immunome Project, and the one book that he would need to keep him company on a deserted island.

The following interview took place on January 25 and February 9, 2018.

 

INTERVIEWER

Where did you grow up?

 

CROWE

I was born in Nashville. Oddly, I was born at Vanderbilt, and the old hospital building (“Medical Center North”) had been converted to a research building. I came back to Nashville in 1995 to join faculty and for 15 years my research laboratories were in the same building in which I was born. I joked with people I might slump over my desk one day and complete life’s circle in one place. 

Over time, my family lived mostly in North Carolina, but also in New Orleans

and Pittsburgh. They were all interesting places to live and explore. I spent a lot of time outdoors as a child. Catching lizards in New Orleans, playing in a pond in Pittsburgh with tadpoles and spiders, and playing in a backyard creek in North Carolina, collecting rocks and minerals. 

 

INTERVIEWER

Research or practicing medicine: did the desire to pursue one come before the other?

 

CROWE

My father is a physician, a radiologist, so I spent a lot of time around doctors, in hospitals, mostly in dark reading rooms looking at films. For a period of time, I helped my father photograph x-rays onto 35 mm slides for teaching purposes, and dictating the names and medical record numbers and diagnoses for transcription, which was interesting. Plain films are interesting conceptually in that the reader has to use expert knowledge of medicine and anatomy and visualize the 2D image in a 3D or 4D manner. This 3D visualization process is not all that different from what we are doing in my laboratory with atomic resolution structures and electron microscopy images.

We also had a lot of medical textbooks around the house when I was a child. I

remember finding the photographs in medical texts grotesque, but also very fascinating. My father also had a set of anatomy books of the fantastic medical illustrator, Frank Netter. I loved those images. I still have my father’s copy of the original Netter that he used in medical school in the early 1960s. I have always been interested in the convergence of visual arts and medicine and science. Netter was the gateway.

 

INTERVIEWER

Who or what were your inspirations?

 

CROWE

Initially in college I intended to become a chemist, but a summer job in a commercial chemical environment convinced me I wanted to be more in a biological or medical environment. I pivoted to pre-medicine and went to medical school. I was fully committed to practicing as a physician, with the idea that I would work in the developing world as a pediatrician and medical missionary. I traveled and worked in various international sites (South America, East and West Africa, Papua New Guinea, Indonesia, China, among others). But during my residency, mentors convinced me that if I wanted to make a large impact on global health issues, I likely could have more impact by developing vaccines than by being a provider on the ground. In truth, I sort of traffic in the world of ideas a lot, so a research career was better suited to my strengths and limitations, and general orientation.

 

INTERVIEWER

In a few sentences, can you describe the objectives of your labs’ research?

 

CROWE

We isolate human monoclonal antibodies from the blood B cells of people who have survived infections, and then we figure out how those antibodies recognize the pathogen and inhibit the microbes. The work is a combination of really basic science (“How do these things work”?) and translational work (“Let’s find a potent biologic drug that can prevent or treat this infection!”).

 

INTERVIEWER

What are your favorite books? 

 

CROWE

I have an unusual mix of interests for reading. Books on art, for example I have been reading books lately by or about Joseph Beuys, the German Fluxus artist, and Jonathan Borofsky, the installation artist, very conceptual stuff. The catalogue raisonné for Gerhard Richter, trying to get my mind around his work. I go back to Point and Line to Plane of Kandinsky periodically. But also, I am sort of obsessed with business strategy books, especially Getting Things Done by David Allen; that book has completely shaped my notion of project management ideas. And a weird sort of collections books, a comprehensive text on Lichens my wife gave me, and some early books of illustration by Ernst Haeckel (Art Forms from the Ocean). And, the Bible. I’m a big fan, studying that one a lot on a regular basis.

 

INTERVIEWER

Favorite books on science? 

 

CROWE

Thomas Kuhn's The Structure of Scientific Revolutions. The ideas have been updated since he first rolled out this seminal work on paradigms, but definitely this book has shaped my notion of how science basically works. And the idea that the data that doesn’t fit what we understand as our models are the most interesting data, not the least. 

And, Flatland: A Romance of Many Dimensions, a little novel of Edwin Abbott's

from the late 1880s. This book has helped me reconcile a lot of seemingly contradictory or confusing aspects of how life and the universe works.

 

INTERVIEWER

What aspect of research science do you wish the public understood to a greater extent?

 

CROWE

The extreme beauty, the intricate complexity of it, the unlimited variations, the joy of discovery. 

 

INTERVIEWER

Although not a new concept, immunotherapies now dominate the headlines as the latest tool to treat cancer. Vaccines, interferon injections, adoptive t-cell transfer, monoclonal antibodies – all have shown promise as potential cures at some point in the last three decades, with some gaining FDA approval. What hurdles, or knowledge gaps, remain to further harnessing the power of the immune system to fight cancer?

 

CROWE

The biggest and most exciting recent advances have been in the discovery of antibodies that unleash the human immune response to fight cancer. We are witnessing a revolution in that sphere.

But there is a related but separate goal, and that is to identify some sort of

structure of molecule that is only found on cancers (neo-antigens or cancer-specific antigens). If we could identify such antigens, we could make antibodies that bind to cancer and not healthy tissue and eliminate the cancer. But so far, it looks like cancers mostly use normal human proteins, but they alter the amount or kinetics of those proteins. So, it’s been hard to find an antigen found only on tumors.

 

INTERVIWER

The Human Immunone Project is a large-scale, open-source initiative to better understand the components of the immune system via sequencing technologies and bioinformatics. As Director of the Project, can you tell us a little more about its objectives and your role?

 

CROWE

This was sort of a ‘big-science’ fantasy I had, which is modeled on the Human Genome Project. The idea is that if you had the sequences of every human antibody and T cell receptor in healthy people on the planet, this enormous database would be of exceptional utility to a wide variety of investigators. The idea was essentially that the Human Genome Project led to the emergence of Precision or Personalized Medicine, and thus the Human Immunome Project could lead to precision immunology and vaccines. We’ve launched the Project at Vanderbilt, and a big team of people is working very hard to make the fantasy a reality.

INTERVEWER

Comparing it to the Human Genome Project, how ambitious is the Immunome Project? Can you provide a relative idea for how the two compare in terms of the data output? 

CROWE

The scale of sequences is not comparable. We don't even know the number, but it's something like 100 billion times the size of the Genome Project. But the consideration is that technologies are so much faster now. Because of the improvements in sequencers and in computing, we can now do many orders of magnitude more work with the same resources. So I'd say it's much bigger, but similar in scale and intent.

INTERVEWER

What about timeline?

CROWE

Yes. Our initial projections indicate about 10 years to do most of what needs to be done, but so far, we are on track.

 

INTERVEWER

Why has our ability to cure childhood cancers outpaced progress in general oncology? 

CROWE

Childhood leukemia protocols were tweaked empirically and iteratively for many years. And these cancer cells grow very fast, so they are also more sensitive to cell growth inhibitors than slower growing cancers. The treatment of childhood acute leukemia is amazingly good now. But all of those advances are basically last-generation technology. Learning how to master the use of broad poisons. The next-generation solutions will be much more targeted.

 

INTERVIEWER

Do you pay attention to how science is reported in the US? If so, how could scientific journalism improve to more effectively communicate the successes and failures of scientific research?

 

CROWE

I give a lot of press interviews, usually when an important publication stirs general interest, and I have interacted with print, radio and TV journalists. I’ve also taken a press interaction course (twice!). I gave a TedX talk (Unraveling the Mystery of Immunity) last year. So, yes, I have thought about how to do this, but I can’t say that I am very good at it. Communicating clearly to the public is difficult for scientists. The central goal is to distill the work to one interesting idea (to come up with a “single overriding communications objective” or SOCO). The best science journalists communicate a lot better than scientists. 

INTERVIEWER

Does the threat of antibiotic resistance keep you up at night? Let's say full-blown antibiotic resistance has its own doomsday clock - how close are we to midnight?

 

CROWE

That's a good question. We're looking very closely at antibiotic resistance because now we have antibiotic stewardship programs. It used to be that we didn't control antibiotic use at all, doctors were prescribing antibiotics left and right in a non-rigorous manner. Now we're much more thoughtful, looking at every isolate in the hospital and how it responds to all available antibiotics. Occasionally, we will see germs that are resistant to everything that we have. There are particular microbes, like tuberculosis, that are hard to deal with and we're seeing some really scary resistance in certain tuberculosis strains. Certainly we're seeing more of this, and that is scary. 

Another concern of course is that we don't have many prospects in the pipeline.

Drug discovery usually takes decades, and if you look backwards at what's in the pipeline, there aren't many new classes of drugs, entirely new compounds that could be introduced in new interventions. So most of what is coming along is minor variations of what we already have.

 

INTERVIEWER

What is the scientist’s responsibility to the public? In the last decade, huge interdisciplinary projects have been deployed to solve some of science’s big remaining questions like eradicating cancer and mapping the human brain. For example, as part of the 21st Century Cures Act, Congress authorized $1.8 billion in funding over the next 7 years for the Cancer Moonshot Initiative. Since 1971 when Nixon launched his “War on Cancer”, $200 billion has been invested in research aimed at cancer therapy development. The advances in life expectancy and tailored therapies enabled by that endowment are truly remarkable, but nonetheless, cancer remains the leading cause of death worldwide. This is a specific example, but when milestones aren’t met for these headline-grabbing projects, how far should scientists go to educate the public on why things didn’t work out as they’d hoped?

 

CROWE

We have to realize that basic science takes time to play out for specific applications. Decades. Most press interactions around major discoveries lead with the question of “when will this be available for patients?” The answer is usually going to be, if we are truthful, decades. But if we don’t have discovery work ongoing, then the answer is never.

 

INTERVIEWER

You’re stranded on an island with a record player and a Blu-ray-player-equipped TV. Let’s also assume this island comes equipped with the food, shelter, and clothing necessities, so you don’t have to worry about those – the only thing to worry about is entertaining yourself for eternity. You can bring five things. What are they? 

 

CROWE

I could probably make it just with a Bible. It’s a very rich source of history, story, complexity, human behavior, the nature of the world, ideas. 

 

INTERVIEWER

After the 2016 election, the idea of scientists coming forward to run for public office gained momentum. If you had to nominate one scientist to run for President, who would it be and why?

 

CROWE

Politics is sort of a mystery to me. We need political systems, but I don’t think normal people want to do this type of work right now, or could survive the weird processes. It’s not based on logical processes that I understand.

 

INTERVIEWER

Two of the 20th century’s greatest writers, H.G. Wells and George Orwell had an ongoing debate over the nature of science and the answers it could and could not provide for future generations. Do you think the world would be a better place if scientists were in control of it? 

 

CROWE

Science is a very limited field in some respects. And scientists are just people with all of the normal strengths and flaws. A lot of us are pretty high on IQ and often low on other intelligences, like emotional quotient (EQ) and spiritual quotient (SQ). There might be some scientists who could run the world well, but the world can’t be run only on scientific principles as they are currently understood.

 

INTERVIEWER

What will be the most impactful discovery in pediatric infectious diseases in the next decade?

 

CROWE

Dealing with antibiotic resistance. An RSV vaccine. Finding the cause of Kawasaki’s disease. Eliminating childhood HIV.

 

INTERVIEWER

What would you say is key to the young scientist’s development? To me, research science and the arts run parallel paths. It’s a career mired in failure (failed experiments, rejections from publishers) that requires obstinate will power and a creative approach.

 

CROWE

Yes, combining creativity with detailed execution. It’s a paradox, but the best scientists do exactly that. And staying in touch with the childhood approach to exploration – play, curiosity, collecting, beauty, complexity and contradiction. Having fun.

 

INTERVIEWER

It seems like it’s all doom and gloom for prospective and current PhD students. Most of what’s written on the current state of academia as a potential career for newcomers is that there are too many qualified candidates for too few tenure-track positions, and it’s exceedingly difficult to achieve a work-life balance as the number of grant applications increases while budgets shrink, not to mention how the Trump administration’s tax plan and its tuition exemption repeal would pose a serious challenge to all incoming students. What advice do you give someone considering the PhD track?

 

CROWE

It’s the best career possible for the right person. People give you money to ask interesting questions and find the answers, in the field of biology where the subject is beautiful and complex. But the career can be challenging if you worry about guarantees of job security in perpetuity, since our support is soft money. I think of it sort of like an art career. Getting paid to make art is a pretty challenging business plan, but for the people compelled to do it, who put everything into it and make it happen, it is a very privileged career. Also, there are plenty of jobs in science that aren’t in the model of the lone mad scientist coming up with all of the ideas. Science is done in teams now. Some of the best and most rewarding jobs in science today involve doing science, in a dynamic team. Being the team leader isn’t the only job, or even the best job these days. Instead, I think the best thing for students to do is practice deep introspection about their natural interests, instincts and talents. Align your career with those things, so that you end up in a job you like and one in which you can perform well. Instead of letting others set the goals or expectations.  

 

INTERVIEWER

If you could have dinner with one scientist, dead or alive, who would it be and why? 

 

CROWE

I’ve been reading the new Leonardo biography. He’s on my mind, very fascinating. 

 

INTERVIEWER

Last question: Rolling Stones, Beatles, Led Zeppelin, or Pink Floyd?

 

CROWE

I listen almost exclusively to African music. Ali Farka Touré, Samite, Rokia Traoré, Myriam Makeba, Angelique Kidjo, Cesaria Evora, Oumou Sangare, many others. 

INTERVIEWER

Follow up to last question: were you exposed to African music prior to your medical missionary work or was it during that time that you fell in love with it?

 

CROWE

I think it was during that time. I had a fascination with world cultures when I was in college, and right after that, went to West Africa and East Africa. Music is deeply embedded in the culture there, and my first exposure was actually homemade cassette tapes and bootleg tapes of pirated African music that people were selling in the markets.

What helped me was during that time I was training Africans who were in their 20s - and they knew the cool stuff. A lot of those guys were listening to Motown on their radios, so they picked it up and put their own spin on it. It's crazy because these are major international music stars, and in the United States, no one's heard of them. 

Learn more about Dr. Crowe and his lab here. For those interested, the most recent publication from the Crowe laboratory describes a new site of human antibody interaction discovered on a protein in respiratory syncytial virus (RSV), representing a potential breakthrough in vaccine development.

Feel free to leave your thoughts on the interview in the comments section below. 

©2019 by EG Lund.