In this exclusive interview, Dr. Francis S. Collins, renowned geneticist and former Director of the National Institutes of Health, reflects on the impact of the Francis Collins Scholars (FCS) Program for Neurofibromatosis Type 1 (NF1) research. Speaking with Dr. Jaishri Blakeley, Executive Director of NTAP, on the program’s 10th anniversary, Dr. Collins shares his insights into the progress made by young scientists in the field and the essential role of passion, innovation, and dedicated mentorship in advancing therapeutic research. From breakthroughs in NF1 and Cystic Fibrosis to his thoughts on the evolving balance between clinical practice and research, Dr. Collins highlights the critical importance of fostering the next generation of visionary researchers. This conversation underscores a decade of achievement and offers a hopeful outlook for future advances in NF1 and beyond.
NTAP is celebrating the 10th anniversary of the Francis Collins Scholars Program. Looking back to 2013, what motivated you to agree to the creation of this program in your honor?
Well, how could I say no? When you approached me, Jaishri, and shared your vision for the program, I was inspired. I deeply wanted to see the research in NF1 go forward at the maximum possible speed. Ten years ago, I noticed that while there were promising projects in NF1, there weren’t nearly enough. We needed more…young, inspired, motivated scientists who would be willing to make this the major focus of their career. That’s how things really move forward. The strategy that you adopted for this program and your wonderful leadership Jaishri, made me confident that this was something I could be really proud of. I’m honored my name could be a part of it.
Seeing the evolution of the program over the past decade and the achievements of the 18 Francis Collins Scholars, what’s your take on the current scope and impact of their work?
I am thrilled to see, the breadth, depth and scope, everything from basic science investigation of how that NF1 gene works, what it does in terms of the early stages of creating tumors, or how it affects brain development. On towards real insights about how to do early diagnosis for the most dangerous type of tumors that happen in NF1 and moving towards more ideas about clinical trials to benefit NF1 patients. Their work has generated over 60 publications and attracted approximately $85 million in additional research funding. Starting with a modest amount of support, the program’s achievements show a significant return on investment. It’s exciting to witness the transformation.
Looking at your broader contributions to genetics. One of your notable quotes describes your expertise in discovering genes for conditions like Cystic Fibrosis, Huntington’s disease, and neurofibromatosis. How would you assess progress across these fields, and what key strategies should we pursue for NF1?
All three of those disorders, Cystic Fibrosis (CF), Huntington’s disease, and neurofibromatosis, had their responsible genes identified a little over 30 years ago. We all hoped at the time, that would lead to a sudden rush of insights resulting in the rapid establishment of clinical trials. That was pretty naive.
The genome is a complicated instruction book, and it’s one thing to be able to identify a misspelling. It’s another to know how to correct the consequences of those misspellings.
Cystic Fibrosis has had the most exciting breakthrough in the development of Trikafta. That means that 90% of individuals with CF now have an oral therapy that extends their projected lifespan rather dramatically, almost to what you’d expect for somebody who doesn’t have CF. That was hard won, and if you’d have asked me 10 years ago, are we going to get there for CF? I wouldn’t have been sure. It just was a long, hard slog of trying to find the right drug therapy that would work, and it cost a lot of money.
Huntington’s disease, however, is still challenging, though we’re making strides with RNA-based therapies.
NF1 is in an in-between phase. We’ve seen success with FDA-approved selumetinib for those most dangerous plexiform neurofibromas, but that still leaves an awful lot of the features of NF1 without a clearly documented, successful intervention. We’ve got a lot of work to do.
What do you think it will take to move forward with NF1?
I think the way we get there certainly requires [an] intense understanding at the genetic and cell biological level of what exactly misspellings in the NF1 gene do to cause all these findings. Then the effort needed to translate that into an idea about a drug therapy or possibly a gene therapy—the only way you get there is to have a critical mass of talented, motivated, visionary, maybe a little bit obsessed young investigators who are going to make this the thing that they care about when they wake up in the morning and when they go to bed at night.
That’s what the FCS program has created. This group of individuals working together, get to know each other, mentored by others so that they’re not floating out there alone – something the program has cultivated beautifully. They’re our best hope to get NF1, maybe not too far in the distance, where CF is now.
Very encouraging. For those of us navigating the balance between clinical practice and research, what are your thoughts on maintaining both versus focusing entirely on one?
It really depends on the individual. I think the dual role can be powerful. Engaging with patients offers an anchor in the reality of what patients are going through. My own work on NF1 in the 1980s was driven by what I observed in the clinic; NF1 was common in my adult genetics’ clinic, and it needed research attention. Some people are totally devoted to the clinical side and they have insights that can guide research. And others are devoted to the laboratory, but are pretty tightly connected with the clinicians who are…Progress can happen that way as well. It doesn’t have to be in the brain of a single person. Sometimes the team can make up for that.
With the success of the Francis Collins Scholars Program, do you think this model could help address other medical challenges?
I’m a huge fan. A modest amount of resources…and figuring out how best to apply them to have the greatest impact. There’s no substitute for getting investigators focused on a problem in a way that’s likely to be a lifelong mission of theirs.
That means finding them at that point where they’re trying to decide ‘what’s my independent research career going to look like?’ — scientists, when they’ve finished the phase where somebody else is giving them a project and they’re ready to make their own decision, that’s what the Scholars program aims to do. And I think the results so far are certainly confirming what a wise approach it has been. Without this program these 18 investigators might be working on something else.
You have secured the support of the most important resource we have, which is the talent of a young scientist.