Called to Create: An Interview with Professor Demetrios Braddock

December 31, 2021 | By Raquel Sequeira TD ‘21.5

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Professor Demetrios Braddock specializes in Hematopathology (diseases of the blood) at the Yale School of Medicine, where his lab studies a group of proteins that are crucial for the proper development of bones. Loss of one of these proteins in a rare genetic disease leads to hard, bone-like formations in arteries and blood vessels, resulting in death shortly after birth. Professor Braddock created a treatment for this disease by designing a new protein to replace the lost function. I spoke to Professor Braddock about his work—both a scientific and a Christian vocation of creation. The following interview has been edited for length and clarity. 

Raquel Sequeira: You work on creating new therapies for diseases that have not been targeted previously. I’d love to hear about how you got into your research and what your goals are.

Demetrios Braddock: When I was your age, at the University of Chicago, I was a Christian. As Christians, in our training we always wonder, am I going to lose my faith? I consciously just said, I’m going to believe in God, and I’m going to be a good scientist. And that’s what I’ve tried to do. How that worked out in my life was that I was a doctor as well as a scientist, and a lot of my friends who were committed Christians went into health care for the poor. Some of them became surgeons and went to Africa...but for me, I felt like I was going to try and do it as a scientist, and so I taught myself about therapeutics, and about creating therapies.

I also paid attention to what I enjoyed doing. There are a lot of disciplines in science, and some of them are really hot, and I did some of those when I was younger, and I hated it...I think God calls us to serve him, but he also causes us to use our personalities to do that. So, I think that’s the first thing: you should always listen to who you are. Listen to your calling, but also listen to what you enjoy doing…

I came up to Yale 17 years ago, and this therapy we discovered happened at about year 12, and it was almost like Moses in the wilderness. My lab was effectively running out of money. But I think God had brought me to that stage… We were studying this enzyme, and it was very, very stable, very well-behaved biochemically. [1] Typically, enzymes fall apart, and they’re fragile, and they’re difficult to handle...And that got me thinking about design and intelligent design. These enzymes weren’t evolved by accident: there was something special about this particular family. That was my first insight, and say what you will, whether I’m crazy or not, I believe that there is a creator who made this particular family, and specifically that this enzyme that we use—the ENPP1––has a very unique role in biology. 

There is this fatal disease in babies—these babies are born and within the first week of life, they code and they stroke, and they have heart attacks, and by six months, half of them are dead. And it’s a very traumatic course for the parents. The therapy to cure these kids seemed so simple to me. Once I had the idea—and I had never done any of this work before, I was more of a structural biologist, and an enzymologist—but now I had to do what we call protein engineering and protein design.[2] It took about three or four months, just on my computer, googling things, and reading papers, and at the end of that I had a design for a drug. And that’s the drug that’s been approved now for humans by European and US regulators. 

But this was kind of a leap, because I would explain it to people, and they would be like, “You’re crazy, but I’ll help you.”

RS: What was it that people thought was crazy about the idea?

DB: That it would work—that it would be potent enough to really take care of the physiological problems that the kids were facing because it was such a simple idea. There were people that are smarter than I am and more successful, and they said, “I’ll help you, but don’t be disappointed, we just don’t know that this will work.” 

That’s the thing about somebody who’s a Christian, and who has that faith, you have the will and the support, the spiritual fortitude, to do things that others wouldn’t do. Because, for you, for me, it’s not about money, it’s not about career, it’s about the principle of the thing. You tend to be more idealistic, and I think that you have to hold on to your ideals and be true to your calling. I felt called to do this, I felt called to try it. 

It ended up working. [3] We were shocked when we knew how potent it was. But then there was a series of obstacles, because we were involved with a biotech company that was going to compete with us and patent stuff around us and take it away. The NIH [National Institutes of Health] doesn’t fund this kind of research, because the NIH’s mission is to fund big medical problems, and this is a very rare disease... But there were babies being born and dying every day with this disease.

So at that point, and by God’s grace, I met Yossi Schlesinger, the chair of pharmacology at Yale, and he helped me raise the money from Wall Street to start a company. It took two years… I honestly didn’t think it was going to work, I thought that my lab would collapse, and I thought that I wasn’t going to be successful. And I was okay with that, but I was not okay with not trying. I was okay with trying and failing. I think as Christians, we’re called to a certain life and we’re called to a certain vocation and to certain principles, and we have examples of people that have done that and failed. And that is okay as a Christian. I think that gives you freedom because you’re not held responsible for your success. That’s in the hands of God. It’s like in Jeremiah, he says, “I’m sending you to the Assyrians, you have to preach to them the good news. I’m not going to hold you responsible if they reject you, but I will hold you responsible if you don’t preach.” And that, I think, is it in a nutshell: the calling of all of our faith...

Nobody expected me, a failing associate professor pathologist, to be able to raise 45 million dollars over Christmas break to start a company, but we did. It’s a very acute need, because these parents call me and the company and they just want this drug because they see their baby dying. It’s hard to watch your baby die slowly over six months. And now that drug is through all of the tests, we’ve manufactured it, it’s in bottles, and we’re simply waiting to get it into humans. 

I share that as a way of encouragement, because I didn’t expect that I would be able to do that. I couldn’t have done that without God’s help, His grace. I think that’s where being a Christian allows us the freedom, if you will, to create, to take chances, to step out on a limb because we’re not ashamed of failing, because failure is actually part of our DNA in a way. And in a sense, we’re all going to fail, because none of us will attain perfection in this world. But we’re called to a sort of sacrificial living.

RS: Thank you so much for sharing about your faith. I think it’s so hard at a place like Yale to put that desire for success on the altar before God. And I love seeing that as freedom.

 I had a couple follow up questions. First, you talked about playing the game of NIH funding. You’re in it with this goal to make the world a better place and to make people more healthy, and yet there is this political or institutional aspect that you have to work around. How does that shape your optimism about the field of therapeutic development?

DB: Personally, I don’t count on NIH funding, because what I do doesn’t really fit into their boxes. It’s a game and you have to get into a certain study section, they have to be comfortable with your system, and it has to be a system that everybody else is interested in. And you have to be willing to make slow, incremental progress on a problem of universally recognized importance. 

To do the kind of stuff I did, where I’m really taking leaps into disease as a physician because I have an insight into a therapeutic approach that is unsupported, it’s not what they do. I think people knock Wall Street, but if it weren’t for Wall Street, that drug would have never been developed. It would be dead on arrival. 

I think we can kid ourselves, if we think the pure, unadulterated, heavy science is done by the NIH. It’s as dirty as any other science, it’s just dirty in a different way. I think you have to just follow your instincts. And if you want to create, as a scientist, you will probably have to look at other funding.

RS: Is there a limit to how much optimism we can have about human creation in science? 

DB: I think there are ethical limits to creating, certainly. Some of these gene editing approaches are dangerous. There were a couple trials that were stopped because it was a gene therapy approach, and the patients developed tumors. It’s a little bit tragic, because you could take those proteins and engineer them like I did, and give them as drugs. But instead, they chose to deliver them as gene therapy agents. You’ve altered that person’s DNA, and they have a tumor, and you know that’s going to be a real obstacle for that patient going forward. So those trials have been shut down. 

When I was raising money, all they wanted to hear about was gene therapy. The fact that I had a protein therapy approach was almost like, “What, are you crazy?” As a physician, you take the Hippocratic oath: First of all, don’t do harm. So I think you have to be conservative, and you can be because there are ways around it right now. 

There are other therapies like spinal muscular atrophy, where these kids are in desperate need of a therapy and the gene therapy works great on those kids. That’s a different story. I think it’s a case-by-case basis where you make the decision: this child is going to die;  it’s better to do something, even at the risk of causing harm down the road, potentially.

RS: We’ve been using the word “create.” It’s not something that I would have applied to bioengineering and therapeutics, but I think it’s beautiful and fitting. 

DB: I think God’s called us to be creative, and He’s called us to care for the Creation, and to shepherd it, and to redeem it through our actions and our thoughts and our lives. That is our calling. Creativity is this fundamental aspect of what God’s called us to do. As a scientist and a physician, I think that translates very readily into what we do in the lab on a minute to minute basis.[4]

RS: I love that. Protein engineering is a clear example, but I think even a really crisp experimental design feels creative to me. It can be the most fundamental thing, but there’s a beauty there.

DB: Right. And I think that’s because we recognize beauty. Socrates believed that you can’t teach truth: it’s inside of you, and you have to draw it out. [5] Aristotle believed that you could teach truth, and that it was hard, but that you could learn it. [6] I guess I’m more of a Socratic, Platonic person. We recognize it when we see beauty and truth, and we respond to it in our soul. And I think that’s what God calls us to.

1. An enzyme is a protein that catalyzes one specific reaction in a biological system.

2. Scientists design proteins using their knowledge of the substrate (the molecule the protein binds to) and of proteins with similar function, as well as computational tools. They can make these proteins in the lab and then test them in animals and patients, like a medicinal drug.

3. The results, including a video comparing treated and untreated animals, were published in the journal Nature in 2015 (https://www.nature.com/articles/ncomms10006).

4. In his essay “Loving to Know,” theologian N.T. Wright also explores the idea of research science as a creative role. God’s people are called not only to steward and praise creation, but also to “a rich vocation of ‘knowing,’ in which the scientist will relish paradigm-shifting discoveries, not least those that contradict a priori theory.” Throughout history, scientists of faith been impelled by love for God’s creation to rigorous engagement with their subject of study. (https://www.firstthings.com/article/2020/02/loving-to-know).

5. See the “Argument from Recollection” in Plato’s Phaedo (72e-78b).
6. See Aristotle’s Metaphysics.

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