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

Episode #124
Original Air Date: 03.01.2021

45 Minutes

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Our Guest This Episode: James E. Crowe

Our guest is Dr. James E. Crowe, Director of the Vanderbilt Vaccine Center and the Ann Scott Carell Professor of Pediatrics, Pathology, Microbiology and Immunology. Dr. Crowe and his project team were responsible for delivering a game-changing medical solution in the battle against the COVID-19 pandemic – the development of antibodies that combat the virus.

Dr. Crowe explains another ambitious project, called The Human Immunome Program, which is aimed at collecting the billions of genetic sequences of antibodies in the human immune system. In 2019 the Crowe Lab completed a simulated pandemic outbreak and developed a record-breaking rapid antibody discovery platform. In early 2020, they were preparing for another simulation when COVID-19 emerged. Hear the fascinating story of how his team pivoted and launched a project with no reagents, no information, and no samples.

Other topics we address this episode are vaccine hesitancy, herd immunity, decision analysis, compliance, and information sharing. James has a number of project managers on his staff, and we hear about the implementation of formal project management procedures in the lab including after action reviews and project management processes and tools.

Dr. Crowe is a board certified pediatric infectious diseases physician and viral immunology researcher. He received five years of postdoctoral training in the laboratory of Dr. Robert Chanock at the NIH, and then completed ID fellowship training in 1996 at Vanderbilt, where he has run an independent laboratory since. His research has been supported by a large number of investigator-initiated research awards from NIH, DARPA, DTRA, and foundations with support of ~ $150M. Dr. Crowe and his team have pioneered development of human monoclonal antibodies as potential treatments for viral diseases.

The Crowe Lab studies the human immune response to infection for a wide variety of major human pathogens, including many emerging infections. In 2019, Dr. Crowe was awarded the Merck Future Insight Prize (a one million euro prize for pandemic preparedness), and was named one of 10 Medifind 2020 Science Superheroes Fighting COVID-19. He was the recipient of a 2020 AAAS Golden Goose Award for his work on COVID-19. A number of vaccine candidates and human monoclonal antibodies developed in the course of his research have been tested in humans, including antibodies for SARS-CoV-2 now in Phase III clinical trials with AstraZeneca.

Favorite Quotes from Our Talk:

“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.”

- James Crowe

“We’re just looking around at the enormity and the complexity of the human immune system and seeing what’s common and what’s rare, and it’s just fascinating. But I think the bottom line is that the human immune system has an enormous capacity to protect, to recognize, to defend. And that gives me a lot of confidence that the future is very bright...”

- James Crowe

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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 James
03:12 … What is an Antibody?
04:17 … Monoclonal Antibodies
06:44 … The Human Immunome Project
09:25 … Secrets in our Bloodstream
12:02 … COVID Response
15:55 … Getting the Team to Pivot
20:02 … Concerning Vaccine Hesitancy
26:25 … Decision Analysis and Risks
28:06 … Deciding on Intellectual Property
34:02 … Formal Project Management in the Lab
36:35 … After Action Reviews
38:01 … Project Management Processes and Practices
42:45 … Get in Touch with James
43:50 … 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?  I mean, if you’re thinking big, big science…

BILL YATES:  We’ve got computers.

JAMES CROWE:  …it’s just money and effort and time.  So we launched into it.  And to date we have collected billions of sequences, and we’ve started making them publicly available.  And we’ve been exploring them to tell people what the immune system is like, the complexity, the organization of it.  When I was a kid there was a show about undersea world – “The Undersea World of Jacques Cousteau.”  And Jacques Cousteau was a diver, and they would just dive, and they would look around with cameras and say, wow, look at that fish, it’s an albino fish at the bottom of the sea.  Who knew?

And that’s a little bit what our experience is like.  We’re just looking around at the enormity and the complexity of the human immune system and seeing what’s common and what’s rare, and it’s just fascinating.  But I think the bottom line is that the human immune system has an enormous capacity to protect, to recognize, to defend.  And that gives me a lot of confidence that the future is very bright for harnessing that information against infection and against autoimmunity and against cancer.  There’s just so much more we can do that we haven’t tapped into.  We’re just sort of seeing it for the first time.  We’re not yet able to harness it.  But the first step is just describing what’s there.

Secrets in our Bloodstream

BILL YATES:  That’s fascinating.  And just the enormity of the data is a bit overwhelming.  But with the power of computers, the power of big data, and data science, it becomes more and more possible.  And the thing that you have pointed out, which I think is the key to this, and which was fascinating to me, is that each one of us, our blood retains a memory of everything that we’ve fought against.  So talk a little bit about that, those secrets that we all hold in our bloodstream.

JAMES CROWE:  Right.  Well, your body does effectively remember the infections it’s had or the vaccines it’s had.  That’s how vaccines work.  They remember for a long time or forever.  The most dramatic example of this to me was we got sort of tricked into doing a project of studying the immune response to the 1918 flu.  So I had some colleagues who were involved in essentially archeology experiments, finding tissues or corpses of people who died and were buried in frozen tundra after 1918.  And the virus sequences were recovered, and scientists remade the 1918 flu.

And at that point we had the virus, but we didn’t really understand how people eventually got over it.  So we were studying hundred-year-old people who were still alive, and we knew that their first infection with flu was the 1918 flu.  And we studied their immune response.  And they’re a hundred years old, and they still have B cells floating around, the cells that make antibodies in their body, which is astounding.  I mean, it really surprised me.  We did the project, but I thought it was sort of a waste of time.

But in fact they were there, and pretty common, actually.  We could see in most older people the ability to recognize 1918 flu.  And you might think, well, that’s not very smart of the body to waste time remembering 1918 flu.  But 1918 flu essentially did come back in 2009.  You’ll remember we had an H1N1 pandemic, it was called.  And that pandemic was actually caused by the 1918 flu that had been circulating in pigs for a century, and then mixed with a bird flu and a human flu.  There was sort of melting pot inside pigs.  So parts of 1918 came back when all the humans who were immune were dying off.

And so it’s just amazing that the body’s pretty smart, knows to remember these things for the rest of your life.  And again, that’s why we use vaccines.  We can vaccinate a child against measles, and they’re essentially good for 10, 20 years, maybe their whole life.  And the same with smallpox.  We’ve done that with smallpox vaccine to the extent we immunized virtually everyone in the world and eliminated the virus from circulation.  So no one gets smallpox anymore.

COVID Response

WENDY GROUNDS:  So this leads us into talking about COVID.  Just weeks after COVID cases started appearing in the United States, apparently your team developed this ultra-fast rapid antibody discovery platform.  And I’m not quite sure what that is.  But the goal you said was to neutralize the virus.  Can you shed some light on that, and your response to the COVID pandemic?

JAMES CROWE:  Right, well, for something like COVID there’s essentially three medical things you can do for people.  You can give them a drug.  People call them “small molecule” drugs.  It’s like a chemical that you would take, a pill.  And there are many drugs we all take.  Aspirin would be a drug, as an example, you’d take for a headache.  So that’s an example of a small molecule drug.  And people looked at Remdesivir and some other things that were like that.  And then there’s vaccines, and you’re familiar with that.  You vaccinate, and the vaccine mimics the infection without causing the infection, and your body responds thinking that it’s seeing the germ, and then you’re immune.

And then there’s a third technology – and that’s what our group specializes in, and I mentioned this before – of taking a blood sample, sorting, looking for rare cells inside that sample and pulling them out, and finding a blood cell that encodes an antibody.  We capture the genes out of that and make the antibody in our lab and turn it into a drug.  And so that’s – the monoclonal antibodies can be used either to prevent or treat infections.  So the problem is in most drug discovery programs like that, or antibody discovery programs, this process takes five, 10 years.  That’s what it has taken in the past.  And to get something licensed to use in human beings has typically taken about 20, 25 years.  And the same for vaccines.  But in a pandemic, that’s not fast enough.

So we’ve been practicing going faster, faster, faster.  And we’ve gotten a lot of support from the United States government to develop technologies to go faster.  And in fact, in 2019 we did a simulated outbreak.  Who knew that a real one was going to happen?  But we did a simulation, and we pushed as fast as we could go from a blood sample to having the drug ready to go and all tested.  And it took us about 78 days.  And we thought we were pretty hot doing that.  That was the fastest it had ever been done.

And we were, in January of last year, in 2020, we were getting ready to do another simulation, and we were all geared up to simulate a bird flu outbreak because that’s what we thought would be the next thing.  And right in the middle of the preparations COVID happened, basically.  In January the first case hit the United States.  And we knew about that, and so I started talking to my group that weekend and saying maybe we shouldn’t simulate.  Maybe we should switch to COVID.  And everyone was against it.  They’d put in a lot of time to prepare for the bird flu.  We had spent a lot of money and, you know.  Everything was ready to go for the other one.

And then maybe a week or two later everyone said, yeah, we’re going to have to switch.  But it was very uncomfortable because we didn’t have any reagents.  We did not have access to what we needed, the blood cell survivors.  There weren’t any survivors in the United States.  There were four or five people who had been infected.  We didn’t even have contact with them.  But we launched.  And that in terms of thinking how to manage a project, we didn’t have any choice.  It was the worst possible way to start a project.  No reagents.  No information. And no samples.  But we just launched that.

And I think we made the right decision because by March we had discovered antibodies.  We gave them to a pharmaceutical partner, or multiple partners.  But AstraZeneca has taken some of those antibodies we discovered in March, and they’re now in Phase III trials and likely will be offered to people shortly.  So we were able to accomplish a discovery program in about three weeks this time.  And part of it was just the pressure of the situation.  We had to do it, we just didn’t have any choice.  We had to respond to the situation that occurred, not the way we wanted to do it.

Getting the Team to Pivot

BILL YATES:  There are so many angles to look at this from a project management standpoint.  So as a leader you recognized, okay, this is gaining some real press here.  This is a pressing issue with COVID.  It had to be difficult for you to go to your team and say, yeah, all that work we’ve been doing to start this next simulation with bird flu, we’re going to pivot.  So you said within a week or so they had kind of gotten onboard with you.  How did you win them over, and how did that week or so transpire?

JAMES CROWE:  Well, that’s an interesting question.  I’ve been working with an executive coach, or actually a team of coaches, for a number of years to learn how to do this because I trained as a physician and then a scientist.  Nobody trained me in management or leadership.  I’ve made most of the mistakes you can make.  And one of the things is thinking you’re the smartest guy in the room, and you have to have all the answers and so on.  And I think that’s a very strong pull for people who are highly motivated individual performers, and I’ve always worked hard and tried to do my best.  But it’s a bad tendency for leaders.  I’ve been working with coaches, how to empower my team to do things that we could never do with more limited vision.

So oddly, I prepared for two years to step out for about three months and do a sabbatical to do some strategic planning.  So that was planned for me to leave on February 9th of 2020.  And in fact I did leave.  I followed through on that.  My wife and I got on a plane on February 8th or 9th and flew to Italy in the middle, blowing up our response to COVID.  And not only that, we flew in to what became the epicenter of the outbreak.  And then I had to essentially evacuate with my wife a few weeks later.  It was just very disruptive.

You know, again, the planning process, I was going to have a very methodical three-month planning process for the next 10 years.  That was the idea.  And that didn’t happen.  We had to respond.  And I was managing the team from Italy with insufficient WiFi and phone access.  Italy’s still on copper wire, actually, their Internet.  So it’s a little bit slower than here.  I had a lot of difficulty doing that.  And in some ways it was a blessing, back to your question.  The team became a self-organizing unit.  They knew there was not enough time for one or a limited number of people to make decisions.  We had to work as a unit and each person take responsibility for themselves.

But it was fascinating to see.  We had a core team of about six or eight.  Our medical center essentially shut down.  You could not come on the campus to do research unless you were doing COVID.  So we had special dispensation for our team of six or eight to come, and I was in another country, and it was amazing that they pulled together.  So I didn’t have to do any convincing.  I think when once people saw how Seattle was turning into a little bit of turmoil, they knew we had unique resources and opportunity and skills, and we needed to apply to that problem.

And then, again, we did not have the situational luxury of planning.  We just had to do it.  I think that the simulation we did the year before was extremely helpful to us.  And also we had done some after-action review of the last year for months.  We said, “What things went well, and what things went poorly?”  And we had sort of done some soul-searching.  Where could we go faster or better?  And we were not blaming ourselves.  We had just set the world record for going fast, but aspiring to go faster.  And I think that after-action review we did in 2019 set us up well to execute in the moment as a team without me telling people what to do.  They just knew what to do, and they were each asking themselves what should I do, not looking to someone else.

BILL YATES:  That’s terrific.  And I’ve been in situations, not with life or death projects, but with projects where the customer is delaying or the data is not accessible.  And being a part of a team like you were, where people could kind of get over that and go, okay, this is not going to happen, we don’t have those reagents yet.  We don’t have the resources and hands that we need to analyze.  But what can we do now?  How can we prepare for that moment when we do have it, and reach a sprint very quickly once we have that data?  So well done for your team and the self-organizing approach they took.


Concerning Vaccine Hesitancy

WENDY GROUNDS:  You’re expressing how you had to speed things up, make everything go at a rapid pace.  I think a lot of the talk that we’re hearing from people is they’re hesitant to take anything because everything was done at such rapid speed.  But now, I mean, we can see that you’ve been doing this for years.  There’s been a lot that’s gone behind the scenes before something was turned out and said, you know, here’s some antibodies, or here’s the vaccine.  But one thing that we’re concerned about is just the vaccine hesitancy that we’re seeing amongst the public in general.  It was a really high percentage of Americans that aren’t willing to take any type of vaccine.  How do you address that vaccine hesitancy?

JAMES CROWE:  Well, first of all, I want to think through the thought process of “fast” and what that means.  So if you say the vaccines were developed and tested very quickly, and I’m used to it taking 20 years, there’s different ways to look at that.  The reason it takes a long time typically to do a clinical trial is that you need large numbers.  So we’re trying to test these things in 10,000, 20,000 people.  And the logistics of testing and thousands of people is challenging.  But you can test 10,000 people in five years, or you could test them in two weeks.  The numbers are the key to understanding is the vaccine working or is it safe.  It’s not really the time, it’s the numbers.

Conventionally, it takes a long time to do large numbers.  But in this case we did large numbers in a short amount of time.  One of the other limitations, frankly, is money.  So normally companies have a certain cash flow, and they cannot just drop $500 million in two weeks on clinical trials.  But in this setting, the United States government made billions of dollars available immediately so the compression of the trial was enabled by that level of funding.  So the vaccines that have been authorized in the United States so far have undergone the exact same rigor and complexity of testing as any vaccines in the past.

So I just want people to understand there were not shortcuts taken in the clinical trials.  They were done in a compressed time with a large amount of money.  But the same number of people were tested as usual.  So I feel great confidence in it.  In fact, the minute vaccines were available at my place – I’m at Vanderbilt.  We’re a major medical center, and I’m an infectious disease physician.  As soon as it was available I was racing to fill out my questionnaire; and, you know, I was one of the first in line.  And I’ve been fully vaccinated with two doses already.

So there’s a little bit of disinformation that, if you think shortcuts were taken, because they weren’t, the thinking of many people in the public about vaccine hesitancy is a general thing.  It’s not just COVID.  And I think it’s unfortunate.  There’s been a long history of hundreds of years, people wonder are vaccines magic; is there something special and weird about them, and risky.  And they’ve been tagged with a lot of just weird thinking, magical thinking.  And that’s been the detriment of many people.

So I think most people – I’m a physician.  I’ve talked to plenty of mothers about decisions about vaccinating their children.  Most mothers, they just want to do the right thing for their children.  They want it to be safe.  They also don’t want their children to get infections that will damage their brain or kill them or give them pneumonia.  So people like mothers making decisions for their children, they’re just trying to do the right thing.  They’re not really hesitant.  They’re trying to make good decisions, and they need good information.

And there’s been a lot of just flat-out wrong, even in some cases intentionally wrong, information about vaccines. I think people get confused.  They have trouble finding reliable sources, and then they’re sort of hedging their bets, and that’s where you get the hesitancy.  So you have some people who just flat out are against it, for reasons that are not scientific or even logical.  And they’re not interested.  But I think the bulk of those 40% want the information.  Is it safe?  Is it effective?  And I think we need to work on the education around that because there’s a lot of disinformation.

And I’m a scientist.  I’m not really a public health person.  I don’t blame people for wanting good information.  But I think we need to fight through the disinformation, get good information, and make good decisions.  And for COVID this is critical.  I think people have seen Tony Fauci in the news. And he got very politicized and so on, his responses.  But what he’s saying is true.  If we get immunity in the population up to about three-quarters of people, this is going to slow down.  And if we only have immunity in about half the people, it’s not going to slow down.

And so he was giving a quantitative estimate of how many people need to participate, and you’re either going to get infected, or you’re going to get vaccinated.  Those are the two choices.  It’s critical that we get enough people vaccinated for everyone to benefit.  So the whole idea of what people call “herd immunity,” it’s true, we need three quarters or more.  I mean, we’d love to have 95% of people immune because that would essentially stop the outbreak.

BILL YATES:  Yeah.  There are two metrics that I just had to be reminded of as I was researching the work that you’re doing.  50 million, so we had 50 million deaths from the 1918 flu pandemic.  Smallpox was even worse, right, 500 million worldwide.


BILL YATES:  500 million, not infections, but deaths.  And smallpox has been eradicated.  So herd immunity and getting those numbers up there, those are good defenses, and I appreciate you sharing that.

JAMES CROWE:  Yeah, well, think about it this way.  We’ve had bioterrorist events in the United States.  People drop anthrax spores, and a handful of people die.  And that was tragic.  But if somebody dropped anthrax spores and 400,000 people died, I think, you know, there would be a clamor. Why aren’t we doing something immediately about this?  So I just find that there’s a lot of weird thinking.  And I’m just asking people, what is logical that you’re trying to do the right thing; and what is illogical where you’re being influenced by sources.  I don’t know where people get their information, but a lot of social media sources are intentionally wrong, you know, they’re manipulative.

WENDY GROUNDS:  No, I agree with that.  I’ve seen a lot of people post things, and I’ve challenged them, go and look at the source.  Where’s that coming from?  Who is saying that?  Are those top scientists?  And generally they’re not.

Decision Analysis and Risks

JAMES CROWE:  Yeah, I’ve been very interested in decision analysis. How people make decisions.  I’ve been reading the past year the Kahneman and Tversky work.  So they got the Nobel Prize for things like how people make decisions or cognitive biases.  So people in general, not just about vaccines, have trouble doing quantitative analysis of risk. And so if you had a 1% chance of losing all your money, but a 90% chance of getting a hundred-fold increase, which would you pick?  Well, if you’re logical you pick the increase at the 1% risk because 99 people are going to be billionaires.  But people often will say I don’t want to lose my money.  And so they’ll make an illogical choice because of the cognitive biases around gaining or losing, and they have a whole list of cognitive biases.

And I think vaccines fall into this a little bit.  So if you say it out loud, would you rather your kid have the full-blown disease and possibly die, or have a vaccine which has a proven side effect frequency of let’s say 3%, and that side effect is fever for a day, or sore arm for five days.  If you think it out logically there’s no question what you would do.  But you have this filter of cognitive biases.  And they affect investing.  They affect all sorts of decisions you make in your life.

And I think these cognitive biases are very strong in vaccine decision-making.  So those are hard to overcome.  But again, I think if people want to do the right thing and are introspective, just be aware of your cognitive biases in this area, as well.  Making the decision, yeah, I think I’ll just allow myself or my kid or my mother in the nursing home to have the full-blown disease, that’s not logical, and it’s not a good decision.

Deciding on Intellectual Property

BILL YATES:  One of the things that I wanted to ask you about was related to the research that you’re involved in.  Because of the type of research you do, you are sharing data – again, you’re at Vanderbilt University.  There are other universities, other research organizations across the globe that you’re sharing data with. 

So I think of some of the challenges that you face with, okay, this is research that we’ve spent a lot of money, we’ve received grants, we’ve had investments at Vanderbilt in order to develop this information.  But it’s so valuable.  And I know it’d be helpful to this researcher in France, or I know it’d be helpful to this university in California.  So talk to me about how you guys make the decisions, both ethically and financially, as to what intellectual property should we share?  How do we go through the decision-making process of what to share and what we need to retain for ourselves?

JAMES CROWE:  That was a great question.  And this area is infinitely complex and challenging.  So, and in fact this set of issues has led me to the world of project management, formally.  So ultimately I hired a person who’s PMP certified and now is portfolio certified.  We’ve hired, I think she manages five project managers in our vaccine center, just to help us with these issues.  So as an example, anytime we’re doing research with human subjects, that is highly regulated.  There’s a lot of considerations around diversity and equity in our research population, consent, if there are children involved, I mean, there’s enormous amount of oversight of that.

So I have essentially a full-time person who manages oversight of human subjects research in my group.  And then the information about their genetics cannot flow to other people.  This is private health information or private information, cannot be posted on a server in another country because that just isn’t acceptable, et cetera, et cetera.  So the health information’s important.  And then the intellectual property you mentioned, we generate antibodies.  Essentially we get the genetic code, which is a series of about 300 letters that encode that.  And that can be used as the recipe in industry to make that antibody.  Well, that can be emailed around.  That could be hacked off of a server. So we have to protect that in order to give it to a company.

And at least in the United States system, exclusive ownership is the basis of developing things, typically.  So our University will make available intellectual property that we discover and file patents on to companies so that they can develop.  And you could say, well, I don’t like people that make money, or I don’t like bad corporations.  But this stuff takes money.  And the companies have a responsibility to their shareholders.  It’s not, you know, it’s not that they’re greedy.  Their fiduciary responsibility to their shareholders and board is to generate profit. That’s the way it’s set up.

So we have to enable that by protecting the intellectual property.  We can’t just pass around these sequences until they’re patent protected.  And even after then, the patents aren’t issued.  So we have intellectual property rights.  Also we’re working on things sometimes like Ebola and other organisms that fall under a set of laws called “export controls.”  So we cannot have unescorted foreign nationals in our space, as an example, and especially from certain countries.  There’s a list of five or six countries that are of a special concern for information about “Category ABC” agents, they’re called, so especially bad agents like Ebola or Lassa and so on.  We have to control that information.

But at the same time we’re academics.  We’re trying to publish our work.  We’re trying to make the information widely available.  And there’s a very strong emphasis on what’s called “open science” now.  So as soon as we know, we want to tell the world to enable a response, say to the COVID pandemic.  So we have these directives coming from some funders that say we expect you to make the information available immediately to the world because we’re a nonprofit foundation.  And then we have other funders.  We have commercial funders who are companies.  We have the United States government.  And those people are telling us protect the intellectual property so that it can be developed in a commercial environment.  So we have all this stuff we’re trying to manage.

BILL YATES:  That’s so complex.

JAMES CROWE:  So I – you know.  And biosafety, we have to protect ourselves, so we have biosafety level 1, 2, 2+, follow those regulations.  And on and on.  I mean, it just – there are so many regulations.  So we’ve had to hire people who like doing this stuff.  And personally I like doing it, too.  I think 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.

I think it’s problem solving, and not seeing it as the obstacle, but there’s a lot of interest in Stoic philosophy in the past year.  I don’t know why.  But sort of the obstacle is the way for Marcus Aurelius.  You can’t go around these obstacles.  If you go around these obstacles, you’re in noncompliance, and you’ll be in jail.  But if you go through them and get to the other side, that is the path to getting molecules out into the clinic to help people.  And we can’t avoid that.  So we have to enjoy the process, not fight it.

BILL YATES:  Yeah, that’s a great description.  We’ve had various guests on Manage This through the years who have had ethical considerations, financial considerations, return on investments, pressure from stakeholders and shareholders even.  And the need, to your point, the need to get this finding or this product to the market as soon as possible, to the betterment of society.  And it’s a fascinating balance.  So I appreciate you talking through that.  I’m delighted to hear that you got some project managers that are onboard helping you with that.  That’s awesome.

Formal Project Management in the Lab

JAMES CROWE:  Yeah.  They’re teaching me.  I, you know, in the lay sense I’ve been a project manager for a long time.  I do  projects.  But the staff members that we’ve hired have sort of reverse engineered me and the group about general principles that, if you’re methodical, are incredibly powerful.  Who are the stakeholders?  What’s the intended outcome?  Who needs to be there?  Who should not be there?  Actually making action plans after every call and meeting with people assigned.  These are just such basic principles.  But you’d be astounded to see that billions of dollars are being spent in science without these fundamentals being executed in the groups that are responsible.

So it’s been very fun for me.  I think we were using some of them.  But to formalize the principles, and to stick to them, and to keep coming back again and again and again, saying, wait, who’s keeping the action plan?  Is there an action plan?  Is there an agenda for this meeting, or are we just getting on the phone?  And it’s just a struggle.  I think it’s sort of like exercise or losing weight, you know, these things are much…

BILL YATES:  It’s a discipline.

JAMES CROWE:  …harder than they sound to methodically apply good principles of project management on day in and day out.  And we need professionals to give us the infrastructure within which we can operate to keep our affairs organized.  It’s like this paradox.  The more and more organized and sort of rigid we get in our processes, the more and more creative we can be in the content.  If we’re creative in the content and sloppy in the process, it sort of breaks down, and we’re not very creative in the science.  So I find that very contradictory in a way, and I’m living in two worlds that are very rigid and very creative at the same time.

BILL YATES:  No, I get that.  I’ve done some research along those lines, as well, where just the way the human brain is wired, so that there’s a healthy reason why I have habits, I have a certain way to drive to work or a certain routine when I get up in the morning, and it frees the rest of my brain up to tackle those issues or challenges that require more creativity.  So yeah, I get that.  There’s a lot of science behind that.  And I appreciate that coming from you guys.

Even the simplicity of seeing the power than the simulation has had in your success, even as you pivoted to focus on COVID, just coming off of that 78-day record-breaking turnaround, and then doing a retrospective, you know, having to look back at that and what are our lessons learned in capturing that.  It was like perfect timing.  Other than your trip to Italy, it was perfect timing for your team to then pivot and take on this challenge that the world’s facing now with this pandemic.

After Action Reviews

JAMES CROWE:  Yeah.  I’ve been a believer in after-action reviews for a long time.  I did a sort of auditing a course in our business school.  So I’m in the medical center, but we’re on the same campus as our University.  So I went to the business school, and I saw case studies of after-action review.  And the one thing we’re emphasizing, were from the military.  Things like friendly fire, you shoot your own person, nobody wants to do that.  There’s no reason blaming somebody because nobody wanted to do that.  And it’s usually a system failure.  And it’s just enlightening the idea that there’s nobody to blame here. 

We’re all trying to do the right thing.  We’re trying to do exciting science that’s pleasing to us and enjoyable, that helps the world be a better place.  That’s what we’re trying to do.  And when things don’t go well, that’s an opportunity to learn how to do it better next time, not blame people.

So that after-action review has been part of our process for a very long time.  And I think we have to teach people that.  When people come in, they enter these meetings feeling very defensive, like I’m going to get in trouble here.  And that’s a struggle, I think, building a safe environment where you can talk openly and say, you know what, I just didn’t follow through.  I didn’t do that.  And then once one person says “I,” then three other people go, “Yeah, me, too.  I didn’t, I didn’t, I didn’t.”  And usually these failures are system failures where three or four people and the process was broken.  It didn’t have checks and balances.  So I think that’s been one of the more powerful things in our process improvement has been after-action reviews.  They’re not common in science, believe me.

Project Management Processes and Practices

BILL YATES:  So you have described some of the project management processes that you guys have put in place.  One of the things that project managers deal with is, is a process sufficient?  Like software off the shelf, is it sufficient, or should we build our own versus buy one?  Can you share with us some of the decision points that you guys face that have led you to go deeper into project management practices?

JAMES CROWE:  Well, I think there’s one thing that’s been kind of a struggle, and that is should you build your own bespoke processes, or should you bring in the knowledge of others who’ve already walked down the road that you’re about to walk down.  So things like I’ve hired for about a decade a group of programmers within our group to build us custom software solutions.  And so we have been building our own system called a Laboratory Information Management System, a LIM system.  And these can be bought.  You can buy them for $5,000, or you can buy commercial ones for several million dollars.  And we chose to build our own because we wanted to be able to change it every day and have it look like we wanted and function like we want.

And I’m about 10 years into this.  Sometimes what I’ve found is that there are ready solutions that may not be as customizable as I dreamed about, or our group dreamed about.  But they’re perfectly acceptable.  So as an example we started using Lean management ideas in our group.  And we were trying to layer Lean principles onto our Information Management System.  One of our team members said, well, you know, there’s a local outfit, they’re actually in Tennessee, that has a software, LeanKit, and they have a very nice graphical user interface that implements Lean boards, and everybody seems to like it.  And so why don’t we just use that software that already exists instead of spending two years building that? 

And we did that, and everybody loves it.  Our secretaries like it, our lawyers like it.  Our scientists like it okay.  And so it solved immediately a problem that we were spending a lot of time reinventing.

So I think once we started realizing we don’t have to reinvent everything, and everything doesn’t have to be perfect, if it’s 80% of what we need, but it’s available here and now for low cost.  So we’ve sort of switched, and a lot of our software implementations of project management principles like Lean we’re bringing in from the outside.  And we mix and match these things.  And sometimes they’re not optimal.  So we’ve been through Wrike and Todoist and Basecamp.  And, you know, we try things.  And sometimes they work for us, and sometimes they don’t.  We use them for a period, and I would call this “design thinking.”  We say, “Why don’t we design a system and use this,” and it does or doesn’t work.

But we worked through a lot of tools, and Slack is the way we talk to day to day.  And then we’re using LeanKit to move things from left to right, and who’s responsible and so on.  So I think there’s a tension between saying there are no solutions in the marketplace for us, we have to invent our own, versus just cobbling together various tools that actually get most of the job done.

BILL YATES:  That makes me feel better, hearing that, you know, just thinking of the brain power on your team and the capabilities that you guys have because this is the classic buy versus build comes up all the time with project managers.  My background’s software, so I’m right there with the, oh, but these are the features that are most important to me, so let’s just build it.  We can get a few coders in here, and we can make it perfect.  And but there are so many benefits to buying something that’s already available and benefiting from those years of development and the broad customer base that influences it.

So I appreciate just hearing that you guys struggle with it, too, and just hearing some of the common platforms that we’ve used and you use, as well.  And I appreciate the flexibility that your team has, too, that let’s try it.  If it doesn’t work, then let’s try something else.  Then we’ll have a better sense for what features really are important and which ones are not as useful for our team.

JAMES CROWE:  Yeah, and we’ve figured out some qualities of, if we’re going to bring in something from the outside, qualities that make it work better.  So if the software has an API, and we could hit the API and integrate it into our ecosystem, that’s sort of a requirement now.  We don’t want things that are on an island.  And then if it has an API we can do “if then, then that” actions that are pretty simple.

So if something hits our website, it backfills to a Google Sheet on a project manager’s desktop.  And they don’t have to look at it.  It just happens.  So we built some simple tools just linking together these softwares.  But they have to have an API and things like that.  So we’re not really software builders.  We’re trying to do science.  So I think learning simple connecting tools and making a decision of what things will work for us has been an advance for us.

Get in touch with James

WENDY GROUNDS:  We really appreciate all that you’ve shared with us and the advice you’ve given.  If our listeners want to find out more about your work, about what you’re doing in the vaccine center, how can they get in touch with you or just follow what’s been going on?

JAMES CROWE:  There’s two places.  People can follow us on our Twitter feed at @VUMC_Vaccines.  And a lot of times we’re showing things in real time, the discovery things we’re doing there, or just photos of people succeeding in a lab.  And then we have a website at CroweLab.org, which takes you to our Vanderbilt website, and you can see all the team members, including our project managers and all the things that they’re working on.  So those would be good places to look.

BILL YATES:  Thank you again so much for making science meaningful and understandable to common folk like me, and just describing to our listeners the type of work you guys are doing.  And we so appreciate your time and your efforts.

JAMES CROWE:  And thanks so much.  And get your COVID vaccine so we’ll all be protected.

BILL YATES:  Exactly, yes.


WENDY GROUNDS:  Listeners, you have just earned some Professional Development Units by listening to this podcast.  To claim your free PDUs, go to Velociteach.com and choose Manage This Podcast from the top of the page.  Click the button that says Claim PDUs and click through the steps.

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That’s it for us here on Manage This.  Thank you for joining us.  Until next time, keep calm and Manage This.

6 responses to “Episode 124 – A Vital Project – Pursuing Antibody Science in a Pandemic”

  1. Gururaj Hebbar says:

    Great podcast, very informative

  2. Carlos Bravo says:

    I got a little lost on this episode. Everyone was talking about monoclonal antibodies for Covid-19, and then started talking about the vaccines for Covid-19. If one takes the vaccine, what’s the point of monoclonal antibodies? If one was to take the monoclonal antibodies, what’s the point of the vaccine?

    Are they putting monoclonal antibodies in the Covid-19 vaccines? I thought the vaccines were just using mRNA gene therapy.

    I could just be showing my ignorance with these questions, but I thought I’d ask.

    • Wendy Grounds says:

      We decided to cover both topics – vaccines as well as the current monoclonal research that Dr. Crowe is doing in his lab and I do apologize if this was confusing. Monoclonal antibody treatment is used for people who are already infected with COVID-19. It only gives a short-term effect and fights an existing infection. The vaccine, however, protects you for longer. It’s not used to treat an actual COVID-19 infection. Thanks for listening.

  3. Nariman Panahian says:

    I thought I would elaborate more to answer Carlos’s question:
    Vaccines are usually given to prevent infectious disease transmission and as a pre-exposure prophylaxis. CDC publishes a recommended vaccine immunization schedule for all age groups. Unlike mAB (monoclonal antibody) treatments, vaccines are relatively cheap and build immunity lasting over 2 to 5 years if not longer. mABs on the other hand may cost thousands of dollars a shot, but many have a short half life of less than a month, and for some diseases require repeat administration. A number of viral diseases may not build strong immunity, so patients (convalescents), after some time are still recommended to get vaccinated anyway. A vaccine intended to protect against one strain of the disease may show inferior/limited protection against other circulating strains like the South African or the UK strain in the case of covid19.

  4. Tamara Hoffer says:

    Great podcast!

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