how the world works
Dr. Andrei Gudkov is in pursuit of a pure and complete understanding of life itself. That pursuit drives his work–he’s at the helm of a new approach to cancer treatment that has the potential to change the world.
As I write, clinical trials are happening at Roswell Park that will determine the effectiveness of Gudkov’s treatment method. It’s not in the textbooks yet, he explains to me. “It is at the very forefront of thinking.”
Dr. Gudkov was born in Moscow, then the capital of the Soviet Union, where he attended an elite mathematics high school and discovered as a teenager that he would not, in fact, be a mathematician at all–he had little interest in it.
“I had to find the path in my life where not being a mathematician would make sense,” he says. “Since I loved everything crawling and biting, anything alive, there was no choice–I went to biology.”
Though he’d stuck to his conviction that math was not his destiny, he would go on to find himself repeatedly drawn to people, places, and areas of study he never thought he’d touch–throughout our conversation I hear the refrains I never wanted to work with that or I had no interest in this followed by explanations of the forces that led him to work in that field or this laboratory.
His mind is changeable. “Science is constant learning from each other.The moment you stop being a student you’re no longer a scientist, ” he says. “And we [scientists] never become adults–what’s an adult? It’s a person who knows how the world is and can explain it. Scientists always live as children. They live at the forefront of understanding; they understand that they don’t understand anything.”
Gudkov joined the department of biology at Moscow State University after graduating from high school. At the outset, he had no interest in studying disease. He wanted to study life, and disease to the untrained seems like just the opposite. But a fellow biologist at the university enlightened him. Viruses, this friend told him, could be Gudkov’s gateway to the fundamental understanding of human life he’d set out to find. Viruses, his friend explained, have been studying human life for millions of years: “Not having their own mechanisms, they’re using ours–so they’re ideal probes for our physiology.”
The young Gudkov’s newfound interest in virology and a series of renowned Russian scientists he had the good fortune of meeting at the University led him to the fields of genetics, and then evolution.
How is virology connected to genetics? And then how does genetic research lead to an interest in evolutionary mechanisms–and how do all of these interests lead a young scientist to the field of oncology?
When Gudkov entered graduate school at Russia’s National Cancer Research Center, the study of the human genome was taking off in earnest with sequencing efforts underway and fascinating new insights into how and why we exist the way we do were captivating scientists, researchers, and doctors around the world.
One such insight was the discovery that sitting dormant in our DNA is a series of ancient viruses. How did these viruses get here? I ask Dr. Gudkov, eager to hear more. I’m enthralled by what he’s saying, because of the subject matter–ancient parasites!–but more, perhaps, because of the doctor’s way of sharing it.
“Everyone was debating, are these the process of de novo assembly of viruses, of genes that became wild? Or are they viruses that came from outside?” He’s narrating what feels in the moment like the oldest, most profound story ever told. “Today we know the answer–everything came from outside ... these are all ancient viruses which invaded and stayed forever.”
During our long and complicated evolution, he tells me, the viruses became part of our genome; now I see where virology, genetics, and evolution meet.
Finally, cancer enters the narrative. The best way to study evolution, if you want to watch it in real time, is to study a tumor, he explains: “A tumor originates in an organism as a selfish creature that evolves, by itself, from the moment it occurs to the moment it kills us. It goes though super fast evolution because it needs to solve so many problems, it needs to learn to live in foreign environments. And a tumor does that within a few years–the speed is enough that within my life as a researcher I have the chance to analyze this process from start to finish.”
I ask what we hope to understand from this analysis, and he replies without a moment’s hesitation: “How the world works.”
After completing two degrees at Moscow State University and the National Cancer Center, he continued his oncology research among the Soviet Union’s top scientists–people, he says, who may have been known worldwide if it weren’t for the closed society in which they lived and worked.
When the Soviet Union fell and Gudkov suddenly had the opportunity, at 34 years old, to travel the world, his future opened up to him: “It is as if you are only allowed to play your game in your yard and now suddenly you’re allowed to do it in a big stadium ... I found myself at the University of Illinois. I was very depressed because I thought ‘I’m already 34 years old, I will never be able to do anything’ because I had to start from scratch. But little by little, somehow it happened.”
What happened? Gudkov advanced from post-doc to professor, began patenting inventions in biotechnology, and in 2000 was invited to move to northeast Ohio to chair the department of molecular genetics at the Cleveland Clinic. Then, in 2007, after attending a seminar at Roswell Park he moved his operation to Buffalo and joined the Center’s staff: “I liked the place because it’s cancer-oriented and it’s ‘boutique’–I hate big organizations because the inertia is very strong, and they’re not good for quick decisions. So I fell in love with [Roswell] and I never regretted it because after 14 years being here I say it’s the best choice of my life.”
Gudkov had set out in 1978 to study tumors for the sake of understanding them, and by extension understanding much more about the world and the living things that inhabit it. He admits with candor that, no, he hadn’t intended to study cancer treatments.
But as he began to understand the evolution of a tumor, the mechanism by which it ravages its victim by evading every effort to kill it, he also began formulating ideas about what modern cancer therapies–surgery, chemo, radiation, targeted therapies–might be missing.
“Now the question is, by these treatments, are we provoking cancer to evolve?” he asks. “The answer is yes, because sometimes, if our treatment is unsuccessful, we have put a challenge in front of the cancer, to select cells capable of being creative. Cancer comes back not from every cell but from some that are more creative than others. As long as we are treating those who are executors of creativity, cancer itself, and not killing those cells which are carriers of that creativity, we will not be able to defeat cancer.”
As Gudkov examined the evolution of a tumor and its genome, then the evolution of living, multi-celled organisms (think human beings) and their genomes, he made a critical connection between cancer and HIV–human immunodeficiency virus–that would lead him directly to those groundbreaking clinical trials happening at Roswell Park right now.
The drugs scientists have developed since the HIV/AIDS crisis of the 1980s work by inhibiting the virus from using its deadly ability to build resistance to the immune system’s defenses.These treatments were doing what he had theorized might be the key to outsmarting cancer: attacking the parasite’s creativity.
“For the first time in oncology, we have a principal opportunity to treat cancer now by distinguishing normal cells from cancer cells not because of their viability but because of their creativity,” he says. “And we are able to stop the very important mechanisms by which cancer can create diversity.”
After years of testing in animals with highly promising outcomes, the research is being applied to treat cancer in human beings. The trials involve taking the well-established treatments that we know to kill cancer cells and pairing them with the new, creativity-inhibiting drug in hopes of preventing cancer cells from developing resistance and evading the initial treatment. This would give cancer patients a chance to avoid the often life-long cycle of treatment, remission, relapse, new treatment–and onward.
For now, Roswell is starting small, treating only specific cancers. “People [in the clinical trial] are given first-line therapy together with the drug, and we’ll see how it works. Within the next two years we will know the answer.” Gudkov is externally as quiet and calm as he’s been since I sat down across from him, but his excitement is palpable.
As our conversation winds down, Dr. Gudkov says,“So you see how I’ve made a circle? We start with that dark matter in the genome which is called viruses. [Then] I learned a lot about cancer and came up to the understanding that cancer’s evolution is the key. So, let’s stop cancer’s evolution–that is my philosophy today. But I’m telling you, you can’t read about it yet. The papers are being written as we speak.”
Gudkov’s search for life’s deepest secrets has led him, and all of us, to this pivotal moment in oncology research. Whether or not his original intention was to change the world, it seems he and his team at Roswell Park may be on track to do just that.