Every year on the 25th of April, the world celebrates National DNA Day; an awareness day celebrating the discovery of the DNA double helix. This year however, commemorates the 70th anniversary of the discovery of the DNA double helix alongside the 20th anniversary of the completion of the Human Genome Project making it extra special.
To highlight how far the field of genetics has come since the discovery of DNA’s structure, we sat down with Dr. Francis Collins, the leader of the Human Genome Project and former Director of the NIH, about his incredible career in genetics from his initial interest in science and involvement in the Human Genome Project, all the way through to his work in the NIH and White House as a Special Advisor to the President for Special Projects. Read the full interview below to learn more about the past, present, and future of genetics research.
Please can you introduce yourself and tell us what inspired your career within the life sciences?
I am Francis Collins. In graduate school, I became interested in the life sciences, studying physical chemistry. I got excited about DNA and realized there were really cool things happening in life science that I had previously ignored because I was focused on simpler questions in physics and chemistry.
This made me change my direction, which was a bit disruptive to life planning, but it was a good thing. I went to medical school, and there figured out that I was really excited about bringing together the science of the human body, which is medicine with genetics and the study of the DNA molecule.
Your predominant research focus in genetics is surrounding the genes responsible for diseases. Why did you choose to focus on this particular area of genetics research, and how has the discovery of new genes responsible for various diseases impacted the field of drug discovery and therapeutics?
For me, the interest in this wonderful molecule, which we are now celebrating the 70th anniversary of its original description, that double helix, was so compelling in this instruction book for human life and all other organisms.
To understand the most fundamental level of how disease happens and what you could do about it, you had to focus on DNA. The idea that one could discover misspellings in this instruction book that would have significant consequences for people’s future seemed like something I wanted to be involved in.
When I started, there were not many genetic diseases where we knew this answer, but over the course of the next 35 years, particularly because of the Human Genome Project, which I had the privilege of leading, we developed the tools to elegantly examine 3 billion letters of the human instruction book and find maybe just one that was out of place.
So-called positional cloning, which I had the chance to be involved in early on, enabled finding the cause of cystic fibrosis with colleagues and has now been conducted for almost 7,000 diseases, giving us hope for better diagnoses and ultimately discovering how to treat or even cure them.
As well as your research surrounding disease genes, you were appointed the leader for the Human Genome Project, an international research project set out to map, identify, and sequence all the genes that make up the human genome. Can you tell us more about your involvement in this project and what impact the success of this project has had on the field of genomics?
I never expected to be asked to lead a big, complicated international project, but I was really excited about being able to read out for the first time all the letters of our own DNA code.
Thirty years ago, I left my academic position at the University of Michigan and came to the National Institutes of Health to try to organize this international effort. Many people were skeptical about it with the limited technology and possible costs.
It was tough initially, but then many got excited about the potential, and I was able to bring on board some of the best and brightest of this generation of scientists who wanted to be part of this.
Momentum began to build, and with ultimately 20 different groups in six countries, we were able to deliver on the promise of the Human Genome Project, discovering that 3 billion letter code, all in the public domain and two years ahead of the expected schedule and at a lower cost, which made a lot of people happy in the US Congress.
This was profound. The foundation of everything about humanity, as far as its biological nature, is written in that code.
It still amazes me, as we are celebrating the 70th anniversary and 20 years since the Genome Project was completed, that 3 billion letters in an instruction book is enough to go from a single cell, which we all once were, to this amazingly complicated developmental process that results in people with consciousness in a brain with 86 billion neurons.
The medical consequences are beginning to appear in a significant way, and this is the part for me as a physician that I am excited about, that the genome is not an academic exercise but may be the best hope we have for the future of medicine for preventing suffering and curing terrible disease.
Every year, the world celebrates National DNA Day, celebrating the discovery of the DNA double helix. However, this year is extra special as it will also commemorate the 20th anniversary of the Human Genome Project as well as the 70th anniversary of the discovery of the DNA double helix. Why is it important to recognize how far genomics research has come over the last 70 years, and what does this day mean to you?
We all note these anniversaries as an opportunity to reflect on where we have been, where we are, and where we might be going next. When history looks back at the scientific achievements of the 20th and 21st centuries, what is going to be on that shortlist?
I think splitting the atom, going to the moon, but also sequencing the human genome because it is so profound in terms of a transformation in our understanding of ourselves and what it means about life and disease and how to manage that. It is not a bad idea to stop and think for a minute about what happened over those 70 years to get us to today and how did that Genome Project effort, completed essentially 20 years ago, begin to empower many aspects of who we are.
It is not all about medicine, either. Another learning is how we are all related to each other. There is no biological basis for anybody to think of other people as not part of the same group. We are all part of one family descendant from a common set of ancestors; genomics made that clear. This is good for us to keep in mind when we seem to be divided from each other.
For the medical aspects, the advances with cancer and where we will be able to go are hugely important. Cancer is a disease of the genome, and now, in any patient who has the disease, we can figure out exactly what is driving those good cells to go bad and what to do about it.
This is transformative and is already becoming almost a standard of care. We can use sequencing of the genome to understand what is happening in a mysterious circumstance where somebody has a disorder, and nobody understands. About 40% of the time, genome sequencing gives the answer.
Discovering all these genes involved in diseases means that we are now on the path to understanding how to cure those diseases. There are some dramatic examples, such as spinal muscular atrophy, where kids never used to live more than a year or two but are now able to go to school.
Sickle cell disease, the first molecular disorder, has one letter that should have been an A but instead is a T, and this causes a very serious illness. We are now curing this using genetic approaches.
Genetic sequencing is still complicated and expensive, and it needs to be more accessible to places like Africa. But the proof of principle is there. I did not know that would happen in my lifetime, and I bet there are many other things I have not expected that will happen in the next ten years.
For people reading this, particularly young people trying to figure out what they want to do with their life, career, and interests if you happen to be interested in science in any way, this is the moment for life science to explode with potential and have all kinds of applications that some of us have not even thought of yet, but are going to be amazing to be part of. We need you.
In 2021, you stepped down from being the Director of the NIH after serving as the longest presidentially appointed director. Whilst serving as the director, you watched the world navigate through a global crisis; the COVID-19 pandemic. As someone responsible for spearheading the NIH’s response to the pandemic, what impact did the pandemic have on the health of the nation, and how important was it to you to design a strategy that mitigated its impact?
When COVID-19 emerged in January 2020, this was the greatest challenge the scientific community had ever really faced, and the response was phenomenal. From every sector, from academic investigators, from the government, from the industry, we all got together and said, “This is a crisis. We cannot worry too much about who is going to get the credit. We just have to bring every kind of skill and talent to bear on this.”
The results were remarkable, including the vaccines. In the past, the shortest timetable to develop a vaccine against an illness was perhaps five years. Most vaccines failed, and the ones that worked generally had a success rate in terms of protecting you of perhaps 50-60%. With the new approach of mRNA vaccines, 11 months from the first glimmer of what the virus was to having those approved for emergency use and with a 95% efficacy better than anybody had almost dared to hope.
That is a truly remarkable demonstration of what science can do in a circumstance like this. I think history will notice that for decades to come. We also had to find therapeutics, and initially, we had to start with things already approved for other diseases to see if they would work, such as Remdesivir. Steroids and monoclonal antibodies also were developed.
