Episode 124 – A Vital Project – Pursuing Antibody Science in a Pandemic

Pioneering the development of human monoclonal antibodies as potential treatments for viral diseases, in 2019 the Crowe Lab did a simulated pandemic outbreak and developed a record breaking rapid antibody discovery platform. Dr. James E. Crowe, Director of the Vanderbilt Vaccine Center shares how in 2020, as they were getting ready to do another simulation, right in the middle of their preparations COVID happened. Hear the fascinating story of how his team pivoted to launch a project with no reagents, no information, and no samples.  Table of Contents 01:37 … Meet James03:12 … What is an Antibody?04:17 … Monoclonal Antibodies06:44 … The Human Immunome Project09:25 … Secrets in our Bloodstream12:02 … COVID Response15:55 … Getting the Team to Pivot20:02 … Concerning Vaccine Hesitancy26:25 … Decision Analysis and Risks28:06 … Deciding on Intellectual Property34:02 … Formal Project Management in the Lab36:35 … After Action Reviews38:01 … Project Management Processes and Practices42:45 … Get in Touch with James43:50 … Closing JAMES CROWE: I like the complexity of it, and I like working with project managers because they like seeing the complexity.  And the bottom line is getting things done in a complex environment.  That’s getting stuff out the other end and not being discouraged by that, but enjoying the complexity. WENDY GROUNDS:  Welcome to Manage This, the podcast for project managers by project managers.  I’m Wendy Grounds; and, as always, here in the studio with me is Bill Yates. Listeners remember if you’re claiming PDUs for our podcast, as well as for our courses, check out our website. Our PDU claim page has been updated with the new instructions.  We are so glad you’re joining us today.  We have a special guest.  This is Dr. James Crowe, and he’s a physician scientist at the Vanderbilt University Medical Center.  He’s the director of the Vanderbilt Vaccine Center and the Ann Scott Carell Chair.  He’s a Professor of Pediatrics and Pathology, Microbiology and Immunology. BILL YATES:  Dr. Crowe has pioneered development of human monoclonal antibodies as potential treatments for viral diseases.  He’s going to describe to us what that means.  I think we’ve all heard about antibodies lately.  But he can describe it from a science perspective.  And they’d done a lot of work on antibodies prior to the COVID pandemic.  But when the pandemic hit, his team pivoted, and we’ll talk with him about that.  In fact, the Crowe team won an award in December 2020.  They were recognized for their work on COVID antibody research, and that’s a fantastic award that recognizes the achievement that they’ve had in that field. WENDY GROUNDS:  Yes.  So he gives some great project management advice in this podcast.  It’s really interesting to hear his perspective.  And also something we ask James is why we’re still debating the social good and the necessity of vaccines.  And he touches on that, as well.  So let’s talk to James.  Hi, Dr. Crowe.  Thank you so much for joining us today. Meet James JAMES CROWE:  Yeah, thanks for having me. WENDY GROUNDS:  We’re just so excited to talk with you today, to clarify some issues about vaccines and about immunization.  And I think you’re just the right person to talk to.  But I want to just go back a little bit and find out what is your mission as a scientist in the vaccine area?  How did you get started in this?  And what really is your goal? JAMES CROWE:  Well, I trained originally as a pediatrician, and ultimately worked in various places around the world.  I traveled in Papua New Guinea and Sub-Saharan Africa and various exotic places, thinking that I might spend my life trying to make the world a better a better place for children who are in challenging situations.  And when you’re there, you see infectious diseases as a big part of the challenge.  Ultimately I trained as an infectious disease specialist to try to work on prevention of disease, infectious diseases, particularly for the world’s most vulnerable people.  And that ultimately led me to science. BILL YATES:  Before we dive too deeply into this, Dr. Crowe, you spell your last name with an “e.”  The founder of our company is Andy Crowe.  He’s my boss.  He also spells it the same way.  So the big burning question that I’ve got to deal with first is are you guys related?  Are you guys cousins or something?  Do you have any idea? JAMES CROWE:  Well, that’s a funny question.  I am working with one of my cousins on a major big science and health initiative right now.  But it’s not Andy, and I don’t think I’m aware of Andy.  But yeah, our family name comes from the U.K., so we’re British somehow back in the day. What is an Antibody? BILL YATES:  Very good.  Well, Wendy and I have watched the TED Talk from – I think it was 2017? JAMES CROWE:  I think that’s right, yes. BILL YATES:  That was so impressive.  You talked about the immune system there.  And it was visually stunning.  I encourage our listeners to take a look at that.  They can find the TED Talk just by, you know, we’ll have a link to it, but they can search your name and TED Talk.  But in that you describe the immune system, and you lay out a description of antibodies.  And we want to talk about that research that you’ve done.  But just help us with some definitions here.  What is an antibody? JAMES CROWE:  Well, antibodies are the body’s natural defenses.  They’re a type of molecule called a protein.  So when your body sees an invading entity like a germ, you swarm around that with lots of cells that are in your blood or in your tissues, and they recognize there’s something foreign there.  And then they mount a response, and they start kicking out these molecules called antibodies, or proteins.  And those antibodies are like your body’s natural drugs.  They protect you by covering the germ and making it inactivated so it can no longer infect other parts of your body, and also so that you don’t spread it to other people.  So antibodies are really the body’s natural defense against infection. Monoclonal Antibodies WENDY GROUNDS:  In your lab, It’s called the Crowe Lab at Vanderbilt Vaccine Center, you’re pioneering the development of human monoclonal antibodies as potential treatment for viral diseases.  So can you explain what is a monoclonal antibody? JAMES CROWE:  Well, the word “monoclonal,” if you break down the Latin, “mono” is one and “clone” is something that’s always the same.  If you make them, they’re identical.  And so in your body’s natural defense, if we took a blood sample, we would find millions of different antibodies, but probably only a few of those are for any particular germ, like flu or anything that you’ve seen before, one of your vaccines like measles. And in our work we search – it’s like searching for a needle in a haystack, and we find the particular individual antibodies in a person’s blood sample that are best suited to inhibit the germ that we’re working on.  So we can find a single antibody that is the key to immunity, and we can remake that antibody in our lab, and we can even remake it in a factory very cleanly and use it like a biological drug. And the beauty of that is then we can transfer that one antibody, that monoclonal antibody, into another person and achieve instant immunity, so we can transfer the best of one person’s immunity into another person, and immediately they have that immunity, which is a very cool thing about how our process works.  And it’s not just a trick, this is used in medical practice now. BILL YATES:  And just for reference, how long have you been at Vanderbilt now?  Because this has been a pursuit of yours for many years; right? JAMES CROWE:  Yeah, it has been.  I started working on monoclonal antibody ideas around 1990.  I’ve been at Vanderbilt 25 years.  I know, because I got a little gold pin this year, and they sent a chair to my house. BILL YATES:  Congratulations. JAMES CROWE:  I started to think, wow, maybe this a sign that the end is near here.  But I got my 25-year gold pin this year.  So I have been working on this stuff a while.  But I have more enthusiasm now than I’ve ever had for this because the technologies in the field of science are converging to allow us to do things with speed and scale and effectiveness that have never been possible.  It’s this very, very exciting time to work in science and medicine. The Human Immunome Project WENDY GROUNDS:  One of the projects that I saw you were working on in your lab, and you talked about this in the TED Talk, was to sequence all these antibodies and put them in a database.  Now, this just sounds a massive project.  What does that mean for immunotherapy, and how is that project going? JAMES CROWE:  Right, well, this is a project that we term The Human Immunome Project.  So “ome” is when you’re studying all the elements of a system.  And we modeled that term on The Human Genome Project.  So when I was a young scientist, I remember sitting in the crowd of a meeting I was at.  And Craig Venter, who was one of the leaders of The Genome Project, was there, saying he remembered when he spent, I don’t know, five or 10 years cloning a gene.  He worked 10 years to get a gene.  And then it started getting faster, and they would get 10 genes in two years.  And eventually the aspiration was why don’t we collect all the genes in the human genome. The kind of dirty little secret there was they didn’t do the immune system genes, which we’ve called the Immunome, because in your immune system you mix and match genes.  You combine them.  And that diversity that you can achieve by combinatorial diversity is sort of like playing cards.  You can make a lot of hands of cards if you mix and match them.  So the immune system can make an enormous diversity, and people did not aspire to sequence or catalog all the antibodies that could be made.  But I started thinking, why not?