By the time you reach adulthood, it is estimated that your body contains 30 trillion human cells, and an equal number of cells of foreign origin (you could accurately claim we’re all at least half immigrant in origin). Each of those 30 trillion human cells derived from the coupling of two gametes, from one zygote. Each cell contains two copies of three or so billion bases of DNA – one from your mom, one from dad – that are packaged into two copies of 22 autosomes and one pair of sex chromosomes. Each one of those 30 trillion cells carries the scars of a million years of battles in their genome, of enemy and friendly fire - from environmental insults, viral invasion, and copying errors. Before you were born, if you were lucky you inherited a genome that would later protect you from most of this historical and acquired damage; regardless, it was out of your control.
Shortly after conception, your genome would replicate with each cell division, and each replication would result in a small number of mutations in the daughter cells’ genomes. Most would be repaired, but some would escape notice. Environmental exposures could cause more errors, resulting in every one of your 30 trillion cells having a slightly different genome sequence. Indeed, we owe our incredible diversity as a species to a million years of these errors. Those mutations that ended up in the germline - and didn’t affect the viability of that gamete - could get passed on to the next generation. But this is not a success story.
Thirty trillion is a very large number, and very large numbers challenge our understanding of probability and risk. If I told you that you had a one in a million chance of being hit by a car today, you wouldn’t think twice about crossing the road. But what if you knew you would cross the road two million times before you reached adulthood? In a way, each of your cells’ genomes has crossed that road many times on your way to adulthood, and each will encounter runaway cars throughout your lifetime. Most of the damage they receive will be benign and repaired. For the remaining minority of cells that cannot be fixed, almost all will be identified by your body’s defense mechanisms and marked for death before they can cause trouble. For nearly half of us, during our lifetime one of those 30 trillion cells will encounter damage or errors that cannot be fixed, and the damaged cell will escape the notice of our front line guards, and these errors in the genome will transform that cell into an enemy.
A year into my graduate studies at Duke University, a post-doctoral fellow named Danielle Maatouk joined my advisor’s lab. Because I had worked in industry for five years and she had gone directly to graduate school, she was actually a few months younger than me. Despite our parity in age, I immediately looked up to her as a mentor. She was an exceptionally talented developmental biologist, but even better still as a mentor and friend. She took every new student under her wings, and taught them how to dissect mouse embryos; and helped them prepare for their preliminary exam; and helped them deal with the stress of grad school.
Danielle was both a mentor and friend. We shared a special bond owing to our similar stage of life. We were both navigating young marriages. I arrived at Duke with my 6-week old daughter Grace in tow, and Danielle would give birth to her daughter Abby while at Duke. We both struggled to balance our work and family lives, and we shared that anxiety with each other. Eventually I graduated and moved my family to Maine to start my own post-doctoral fellowship. Danielle succeeded in her post-doc and moved her family to downtown Chicago to start her own lab at Northwestern Medical School. We kept in touch by email and occasionally by phone, and once we met up in Maine to camp together – by then I had a young son Dylan. After starting at Northwestern, Danielle had a healthy son of her own, Leo – named after her father. Hers was shaping up to be a well-deserved success story.
But then it wasn’t.
The improbability of very large numbers created an enemy. Shortly after giving birth to Leo, doctors discovered a tumor in Danielle’s colon. Danielle understood the initiating event that transformed her healthy cell into an enemy, and later produced a tumor, likely occurred many months or years before. But after hearing the news, I was struck how grateful she was that they hadn’t noticed it during her pregnancy. Danielle always tried to focus on the silver lining. A biopsy showed the tumor to be malignant, and surgery soon followed. Then chemotherapy, and radiation, and another surgery, and an experimental immunotherapy; for two and a half years she was cut, poisoned, and burned, seemingly without end. And yet, she continued to live as if nothing was wrong. With the help of her amazing husband (and her lab manager) Chris, she built her own lab and began mentoring her own graduate students. She was an active mother who attended every school and preschool function, despite being in incredible pain throughout. She became a patient advocate for other people going through the same hell. She continued to reach out to old friends and make new ones – she always wanted to know how I was doing, how my family was doing.
Despite the long odds, part of me always believed, “Danielle will beat this.” If anyone could, it would be her. I would reassure myself that seven billion is another very large number. With seven billion people on this planet, why couldn’t she be the one outlier, the exception to those damning statistics?
Dr. Danielle Marie Maatouk (1977-2016)
Danielle died on Sunday morning, November 13, 2016 at the age of 39, after a 2.5 year battle with aggressive colorectal cancer. She is survived by her husband, two young children, her mother, two sisters, and many friends. She inspired us all in health and especially in sickness.
I write this blog post from my window seat on a plane to Chicago, on a clear night looking down at millions of lights, and reflecting on very large numbers. As a scientist, I’m amazed at the improbability that our species could survive and thrive to this day. I know I should be awed by the fact that 30 trillion cells can live in harmony, that our defense processes have been so exquisitely tuned by evolution. But tonight, I can only think about the one cell that escaped those defense mechanisms. The one that killed my friend.
Rest in peace Danielle. You are dearly missed by so many.
Please consider contributing to the education fund established for Abby and Leo. [Link]