On a chilly winter morning in 2008 I found myself walking down a street, in Urbana Illinois, with an insulated foam container under one arm and a piece of paper, still warm from the lab’s printer, in the other. Inside the container, surrounded by ice, was a foil-wrapped rectangle about the size of a slice of toast. Inside the foil, covered in a special sealing tape, was a plate made of hard plastic, divided into 8 rows and 12 columns of individual small plastic tubes, 96 in total, each about the size and shape of the sharpened end of a pencil. Inside each tube, protected from the outside world by the layers of packaging and floating microscopically in less than a raindrop of ultra-purified water were tiny bits of DNA from an Antarctic animal that lived years ago and thousands of miles away. The DNA was once coiled inside the blood cells of a large mysterious creature known as the Antarctic toothfish (scientific name Dissostichus mawsoni) as it swam the ice-laden depths of the Southern Ocean next to the Antarctic continent. A month before, during a scientific expedition to Antarctica, I had wrestled one of these fish up a high-strength steel fishing line onto the sea ice, drew some blood with a syringe, then meticulously extracted its DNA, cut it into manageable pieces, and inserted it into a bacterium. The strings of DNA in my plastic tubes, part of a gene in the species’ genome, performed the same function in the tube as it had inside the Antarctic fish: it coded for an antifreeze protein. The difference now was, instead of being read by the intricate microscopic machines inside the fish’s cells and converted, by a symphony of reactions, into an elegant biological antifreeze molecule, the pieces of DNA in my tubes were on their way to be read by a man-made machine sitting on top of a nondescript table at my University’s DNA sequencing center. After years of training in the classroom and the lab, I was finally doing real science.
As seen through a powerful microscope this cell, like those in your body, uses the information in its genes to perform its function, a process we are still working to fully understand. It takes publicly-funded scientific research and years of hard work to understand how the same genome can be used for a cell to decide whether it will metabolize toxic substances in the liver, transmit electrical impulses in the brain, or divide unchecked into cancer.
Growing up in rural northern Iowa I didn’t have a clear idea what real science was or what real scientists did. We didn’t have a science PhD in our town or even our county, that I know of. There were depictions of scientists in TV and movies, more often than not in long white lab coats pouring colorful bubbling liquids from one flask to another, designing the main character’s gadgets or holding the world hostage as his evil nemesis. In real life we only heard about science filtered and simplified through news reports, consumer products or government regulations. When I was growing up on the farm in Iowa I didn’t know what a scientist was or what they did.
You go to doctors to understand your health, plumbers to fix the pipes in your house, and accountants to sort out your taxes. But where do you go for your science? We didn’t then and we don’t now, for the most part, have direct access to scientists like we do to doctors, plumbers and accountants. In the real world their work filters down through the technology we use (new phones and airplanes, for example), the new tests or treatments we get at the hospital, and through the news when we hear about the spreading of a disease from mosquitos or a new environmental regulation to do with air pollution. We see, sometimes, a researcher interviewed on our favorite talk show. But, where I grew up in Iowa, we didn’t have a local scientist to ask questions or point us to knowledge on a certain topic, we didn’t go on a regular basis to the scientist’s office or have a scientist over on a house call to solve a problem. From the farm, the whole scientific enterprise was a far-away and abstract thing that didn’t directly affect our lives.
Growing up where I did prepared me to deal with problems as they arise, speak with certainty and work toward simple and predictable goals. We worked hard on the farm, fixed things that needed fixing, planted in the spring and harvested in the fall. We went to church on Sunday, ate meat and potatoes at night, and generally trusted the foretellings of the local weatherman. None of that prepared me for real science. But now, after years of study, I’ve become a scientist. I do biological research, moving between cities, states, countries, following the ebbs and flows in knowledge, research interest, federal funding, and the scientific job market. No matter where life takes me, though, it is always a comfort to come home to the farm, away from traffic and smog, where life is simpler and, more or less, we can do what we want.
That’s why it was great when, after I got the PhD and secured a two year research position in a lab in Belgium, I was able to go back to the farm in Iowa for a while. My parents drove from the farm to the far side of Illinois and sat in the back of the room with love in the hearts and tears in their eyes as I defended for my PhD, poring over the effect of stress through the generations in a small wild fish. They were glad, too, when I told them I planned to move back and spend the intervening time on the farm helping with chores while the Belgian visa was processed, in a couple of months after I had submitted the dissertation. Little did we know that, before I had made it home that summer, dad’s cancer would be back.
The cancer, having originated more than 20 years previously from a rogue epithelial cell in his sinuses, had been steadily growing but kept in check by the occasional dramatic surgery to remove the tumors and surrounding tissue of his face, including his left eye, and radiation to destroy cancer cells missed by the surgeries. Now, though, it was growing faster, spreading throughout his body to his neck and lungs and brain, and no longer easily treated with surgery and radiation. I sat next to my parents in a meeting with his neurosurgeon who was explaining the remaining options my father had to battle the malignancy. According to what I knew of the biology of cancer, it didn’t look good. The only remaining option, besides doing nothing, was an aggressive regimen of chemotherapy known in the few patients with his particular brand of cancer to have been mostly ineffective. In combination with the growing masses in his body and brain, the chemo sapped the strength and size of the man I once knew as my strong, resilient farming father and, as one of my siblings put it, “made him age 20 years in a few months”.
My dad, the farmer, sporting his characteristic mustache and carrying me on his back.
A few months later my dad, mom and I sat in an exam room at the Mayo Clinic, listening intently to my dad’s doctor explain how all the surgery, radiation and traditional chemotherapy were, despite their strong negative effects on his body, not slowing the growth of the tumors. The rounds of chemotherapy, drugs meant to prevent quickly dividing cells from dividing, had even caused his beloved mustache to fall out. Aside from one fleeting memory from my early childhood that mustache had been proudly displayed along dad’s upper lip my entire life. My dad, normally an eternal optimist, slumped in his chair at the doctor’s news. Unable to muster his classic lighthearted brand of hopeful pragmatism, he was crushed by the thought that the months of toxic pain and lethargy brought on by the drugs had been spent in vain. Then the doctor mentioned a genetic test, something they could order to be done on a biopsy of the tumor they had removed during his last surgery.
Genetics? My ears perked up. As did my parents’ ears; and right on queue as they had done countless times before they took the opportunity to describe to the doctor that their son sitting here with them has a PhD in genetics (actually molecular biology – but since in conversations with their friends that often comes out as “microbiology”, the study of bacteria and other microbes, and since the distinction between genetics and molecular biology is not all that clear to the general public anyway – I’m ok with them saying their son studies genetics). I asked the doctor to explain the test and asked some useful questions, excited about the potential to make good on all the parental bragging. The test would involve extracting DNA from the tumor biopsy that had been taken during a previous surgery and running it on a gene chip, a sort-of quick interrogation of the forms of genes his tumor might have.
The doctor handed me a colorful glossy sheet of paper with a list of several dozen genes printed on it – the genes that would be interrogated on the gene chip. It by no means would guarantee a useful result; the process that a cell has to go through to become cancerous is just starting to be understood by researchers. Suffice to say it is complicated. Cancer is not a single disease but instead seems to be a common result of many different diseases or causes. A common way for cells to become cancerous is for the genes that control the cell cycle – which normally act as molecular brakes to keep cell division slow and steady and safe – get mutated, broken, preventing them from stopping that runaway process we know as cancer. Dad’s doctor was proposing to read the sequence of those handful of genes known to regulate the cell cycle and act as brakes on cell division, to see if their pattern could be of help in fighting his cancer. Knowing which, if any, of my dad’s genes had mutations would allow the Mayo doctors to compare his case with cancers from other people with similar mutations, perhaps some they didn’t realize were similar using more traditional diagnoses. Using their information on which chemotherapies worked best on that specific genetic type of cancer would allow the doctors to tailor a chemotherapy regimen to maximize the chance of stopping or slowing the cancer. It wasn’t a guarantee or an easy fix, but as my dad stared out of the waiting room window at the Minnesota winter, still reeling from the doctors’ news that the months of chemotherapy hadn’t worked, I reminded him that hope wasn’t lost, there was still reason to be optimistic about this genetic test.
While I was in grad school training to become a researcher my dad and I would have long conversations on the phone, ranging from cars and machines and farming to biology and philosophy and family history. Sometimes we would even talk politics. Most often that would take the form of my dad, a devout conservative, denouncing the liberal agenda that he was convinced college students were being indoctrinated with. He was half joking, I would think, half not. He would nudge, not bite, seeming to me like he was seeing if I would listen to something potentially upsetting to a liberal mindset. And I listened. I would listen, but as a rule with my dad I wouldn’t engage. I worried that engaging with other people on the far-right only led to further entrenched beliefs on both sides. We might be discussing some of my research, or a study that I had read that I thought might interest him, and the nudging would begin. I remember one time in particular I was nearby campus at a sandwich shop grading exams when he asked a fundamental question, “why do research at all?”, and topping it off, tongue-in-cheek, with more about the liberal college brainwashing agenda. I listened, as usual, but then decided it was time, finally, to foray a bit further into the void.
So I put away my grading and had a long, surprisingly fruitful conversation with my conservative dad about why I had chosen to do research and why it might have seemed to him like part of a liberal agenda, expecting that a lifetime’s worth of Republican dogma would soon come thundering down. I explained that, from my perspective, research requires at its core our admitting that we don’t know something. That seemed to me, from a conservative viewpoint, too progressive of an idea. Conservatism, by definition, holds that by and large things are fine how they are (or were) and should be kept that way. It makes sense that someone with that ideology would see higher education and research as strange, superfluous, a waste of time. Why, after all, if we already know how we want our lives to be should we ever ask fundamental questions about the world? The problem with that ideology, and the reason this son of a conservative Iowa farmer chose to go into research and higher education, is that things change despite our wanting them not to, and there are fundamental things we don’t understand. We need people who think and act conservatively, I think, but we also need people who ask hard questions and try to understand the how’s and why’s. That was my explanation, more or less. To my great surprise my dad didn’t go on a tirade or double down or act dismissive. He smiled, somehow, through the phone and said in a upbeat tone “Ok. I understand”. Later, just before we learned that his cancer had returned for the last time, he sat on the edge of his seat at my PhD talk and asked a lot of followup questions afterwards. I think its safe to say he was proud that his kid had started down his own road with a big step, and was seeing it through. But I like to think, even more than that, he was proud that he raised someone willing to question, think, engage in uncomfortable arguments, and treat those who disagree with more patience and respect than we feel they might deserve.
Driving between the farm in northeast Iowa and the Mayo Clinic in Minnesota for his monthly checkups, scans or chemotherapies we had a lot of time to talk, and I was happy to be able to provide emotional support when my dad needed it (as a proud Iowa farmer, and a consummate jokester, he rarely needed it). Our conversations about science became less confrontational. Sitting with him in the doctor’s office, being able to ask useful questions of the doctor and explain in plain English what the genetic test was and what it had the potential to do, I finally felt like my chosen career in research and my PhD in molecular biology could actually help my dad. It was a major surprise and demoralizing to say the least, then, when the results of the genetic test came back inconclusive. That was all they said, inconclusive. How the doctors explained that result is that there were no common genetic variants detected – none of the handful of genes they were looking for that are commonly found mutated in cancer cells were mutated in my dad’s case.
Well…shit, I thought. I already know what that means. The doctors explained that it’s possible mutations in other genes not on the test and not yet known by science to be associated with cancer (there are northwards of 20,000 genes in the human genome, only a smattering known to any depth) could be the cause of my dad’s specific illness. Or epigenetic marks – modifications that cells make on top and surrounding DNA that controls the expression of genes – could be the culprit. I nodded, understanding in so many words that the basic science of genes, epigenetics and cancer was not yet to the point that it could be easily and quickly applied to my dad’s case. The doctors could help dad, I could help dad, by sequencing his entire genome and epigenome, digging through all the information and comparing it to the vast troves of research, designing treatments to specifically target and clear this cancer from his body. The only problem is, those troves of information don’t exist yet, the easy affordable sequencing of a person’s genome and epigenome doesn’t exist…not yet. Studies are on their way, for example one recently published shows that the number of copies of some genes can be amplified in cancer cells, which also wouldn’t necessarily show up on a simple genetic screen like they did on my dad. The point is even if my dad were alive today and we could somehow obtain all of his medical and genetic information and all of the relevant research, there isn’t yet a way to quickly compare and come up with an answer and treatment that could save him from that downward spiral.
People since ancient times have tried about anything you can think of – from spells and potions to ionizing radiation – to get rid of cancer. We’ve tried to pray they go away and use magical remedies that we really really want to work. But cancer cells don’t care about your religion or political ideology. Whether you are conservative or progressive, Democrat or Republican, Evangelist or Buddhist, they will divide just the same. They will continue to divide, unchecked, because that’s what cancers do. It’s what makes cancer cancer. Our best bet, our only bet, against cancer is to take a step back and try to understand the natural processes that govern cells, how they divide, how their genes and the environment interact to determine their behavior, their cancer-ness. We understand some things. For example we have discovered that certain chemicals interfere with pathways that control a cell’s ability to divide in two, an understanding that, when applied to medical practice, led to the treatment we know as chemotherapy. But, as with my dad, chemotherapy doesn’t always work, and it has nasty side-effects. The same goes for surgery and radiation. We’ve put countless time and money into applying what we know, and it has helped give us a little more time or with specific types of cancer, but it hasn’t cured it. Cancer is complex and, if even one cell escapes, it will pass on that ability to adapt and escape so that the same treatment becomes less effective. And to be frank that’s what you get when you apply an incomplete understanding of basic biology to treating a complex biological problem.
Cancer is, admittedly, a convenient example for me to use to outline the need for basic science because its personal. But bacteria and viruses don’t care either; they will infect you just the same. They will come by while we are arguing about whether we believe in evolution or vaccination or the right to health care and devastate us just the same. A molecule of carbon dioxide equally doesn’t care which of its properties you do or don’t believe in, it will reflect heat back into the atmosphere just the same. The global climate is changing, and it has no obligation to avoid changing in a direction we find disastrous. I’m not a microbiologist or a climatologist, or even a cancer biologist, but I understand the studies, the concepts and how their findings are interpreted and applied. I know the incredibly high bar each study must pass before it is ever published and ever reaches the public eye.
The view from the driver’s seat of our dad’s iconic yellow 1970 GMC pickup truck. Trying to understand the perspective of those we disagree with, as I came to do with my dad with regards to research and higher education, is essential I think if we expect the favor to be returned.
The point is, there’s more to know about the real world than any one person can possibly learn in a lifetime. We can’t know every plumbing system and bit of tax code and clinical test so we rely on plumbers, accountants and doctors to understand and translate it for us. In the realm of science there is so much information that it can be daunting even for an expert to stay current in their own small field of research. Breakthroughs in science that solve big problems, like cancer, now come from team efforts, troves of data and often from directions we didn’t expect. It may very well turn out that basic studies in immunology or genetics, discovered in an obscure almost-overlooked creature or biological process, will lead to a cure for cancer.
But for that to happen we have to as a society embrace not just the people and the products of science, but the process of science. We have to fund and do the basic research so that it can be ready as a life-saving treatment when someone else’s dad needs it. Since that cold winter morning when I was walking down the street carrying little bits of an Antarctic fish’s DNA I’ve learned so much more, not just the findings of science but the behind-the-scenes of the scientific enterprise itself. I’ll save the details for another time, but suffice to say I’ve seen no evidence of the liberal brainwashing agenda my dad was half-joking about. But there are crises. When it comes to funding in science it is already tougher than most people outside of the field can imagine. So many real scientists spend so much time and energy writing stellar grant proposals that are not funded simply because the money isn’t there. Without the funding the research proposals stay on paper. And that’s not to mention the kind of salaries we are paid (I have to admit, somewhat embarrassingly, that only once I turned 33 years old did I finally break $30k/year).
We’re not in it for the money, obviously. We’re in it for the awe of discovery, that humble feeling we get when we understand something for the first time, and ultimately for the service we’re providing our society. But the work we do, the actual costs of running experiments, takes money. It takes funding from taxpayers because the questions that need to be asked are not those whose answers will provide immediate returns for shareholders, but will provide long-term returns for society as a whole. Now our representatives are talking about shrinking that already inadequate funding even smaller. Politics seems to find its way everywhere now. We are self-selecting who we choose to be around, dismissing and villainizing those we disagree with, even the facts that we disagree with. That has no chance of curing cancer. Science does. We must realize that scientists are real people who have hopes, dreams, faults and passions, and who are working for us the same way our plumbers, accountants and doctors are. We have to roll up our sleeves and give those folks we find disagreeable our patience and respect. And we have to avoid unchecked division.