From Darkness to Sight

by Ming Wang

  I first met Dr. Church at his eighth-floor office in a building just off the quad. The walls were lined with diagrams of human gene sequences, colorful patterns of G, A, T, and C, the letters that represent the four nucleotides in DNA. For all the complexity of a human organism, there was a dazzling simplicity in the array of these four letters. His office reminded me of Tian-ma’s walls in his bedroom back in Hangzhou, all lined with drawings and poetic verses. Here I was encountering poetry of another sort, no less beautiful in its expression of humanity.

  The year I entered Harvard was a fascinating time for molecular biology. The Human Genome Project was just getting underway, and Dr. Church had been one of its initiators. In just a few years, more than a thousand researchers from sixteen institutions and six countries would join in a global effort to sequence the entire array of three billion base pairs of human DNA. Every scientist involved, including Dr. Church and myself, hoped to understand more deeply how genetics contribute to human disease, and then use the discoveries to develop more effective treatments.

  Sequencing the entire human genome, though a crucial and massive undertaking, would only be “the first step in a 10,000 mile journey,” as the Chinese saying goes. Once the patterns of Gs, As, Ts, and Cs were sequenced, scientists would then have to interpret what the sequence actually meant. Reading this blueprint of life but not knowing its interpretation was like walking into a library, opening a massive chronicle and seeing nothing but scrambled letters. In order to interpret the meanings, we have to learn the grammar behind the letters, namely: what were the functions of the genes and how genes were turned on or off? Why did some people with genes for certain diseases develop the condition, while others do not?

  During our first meeting, I told Dr. Church about my previous studies in chemistry and physics, and how I hoped to better understand disease at the molecular level.

  “I can tell that you’re genuinely interested in the technical aspects of medicine,” he told me. “I’m very pleased to work with a fellow physical chemist.”

  Dr. Church and I began a unique and ambitious project. As the Human Genome Project progressed, larger and larger segments of DNA were sequenced and more genes were discovered. The next major challenge was to develop better technology to study the functions of these genes and how they were regulated. The mere presence or absence of certain genes and mutations did not necessarily lead to disease. More often it was the activation or repression of such genes that caused diseases such as cancer. Since large, complex proteins are the molecules that regulated gene activity, Dr. Church and I wanted to develop a new technology to study the DNA-protein interaction and the regulation of gene expression, and we wanted to do it inside a living cell.

  Up to that point, most studies had examined the interaction of proteins and genes in vitro, that is, in an external environment like a test tube or a petri dish. We wanted to develop a technique to explore the interaction of DNA and protein in vivo, that is, inside a living cell. We used the E. coli bacteria as our model genome system. If we were successful, then the methodology that we developed could possibly be applied to the human genome once it was sequenced within the next decade, which would have a tremendous impact on medicine.

  Outside of Dr. Church’s lab, I experienced the miracle of biology and genetics in my own personal life as well. One day in the spring of 1988, not long after Dr. Church and I had started our project, Shu called me from West Virginia to tell me that she was pregnant.

  “I’m going to be a father!” I told my classmates excitedly.

  Shu and I were both thrilled that we had a little one on the way, but the excitement was consumed by anxiety. We were both in medical-school and we lived six hundred miles apart. During the first two years of our marriage, we only saw each other for a total of two weeks, usually on school breaks and holidays. We were neck-deep in classes, research, and rotations. We could barely nurture our marriage, so how were we going to care for a newborn?

  Our son Dennis was born on December 5, 1988. At his birth, the obstetrician let me cut the cord that connected him to his mother. It was such an awe-inspiring experience to play a part in bringing new life into the world. I’d had enough training to evaluate his Apgar score, the measure of a newborn’s health, and I rated him 9.5 out of 10. Maybe I had paternal bias, but he did come out kicking, crying, and completely healthy … and with so much hair! I’d never before seen an infant with a head of hair like that!

  Shu took a month off school, and I spent two weeks with her and Dennis. We scrambled to figure out a plan to care for our new baby. Once we returned to our respective medical-schools, my parents were able to provide much needed help since my father had finally arrived from China earlier that year, so he and my mother were living with me. Dennis was shuttled between our place in Boston and Shu’s parents’ home in Maryland until Shu and I finished school. In the end, Dennis’s grandparents were more like parents to him than Shu and I were. I would later regret not taking a bigger role in Dennis’s upbringing during those early years, but at the time I didn’t know what else to do. Medical-school was an all-consuming endeavor, and success or failure would determine the course of our careers … and our lives.

  * * *

  Becoming a parent is a rite of passage in many people’s lives. About a year before Dennis was born, I encountered another rite of passage, one that all medical students experience. Before I ever welcomed new life, I was face to face with death. Like doctors in training have done for hundreds of years, I encountered my first cadaver in the gross anatomy lab. Walking into this cold, clinical setting reminded me of being in the anatomy lab at my parents’ medical college in Hangzhou long ago, with the glass jars of floating body parts, the coffins behind the bookcases, and the vivid nightmares of dead people in search of their missing organs. This time there was no escaping the dead bodies. I couldn’t run away like I had done in my nightmares as a teenager. Standing over that steel table rattled me to the core.

  But not as much as having to make that first incision.

  My lab partners and I were assigned a female cadaver. I kept reassuring myself, “This isn’t a human being anymore. It’s just a body.” Mortality stared up at me from her lifeless face. At the end of the semester, her body had been cut into hundreds of pieces and put in boxes labeled by bones, muscles, or ligaments. This woman had donated her body for our education. While I was tremendously grateful to her, I couldn’t help but wonder: was this it, the end of our lives?! What was the purpose of life itself? Or was there one at all to begin with?

  Many doctors point to cadaver dissections as the starting point to becoming desensitized to illness and death, but the opposite happened to me. I actually became increasingly sensitive to life, growing more and more curious about the origin of life, the complexity of the human body, and the determination of whether there was any meaning to it all. I had previously held the singular conviction that science alone was the key to understanding life. It taught that life had occurred and developed by random chance, which meant there couldn’t be any inherent meaning or purpose behind life itself. But the deeper that I delved into the wonders and intricacies of living things, the more I began to question everything I had once believed.

  My dad used to say, “Master mathematics, physics, and chemistry, and you can go anywhere in the world you want to go.” I had come to medical-school with a unique amount of experience in physics and mathematics, so while other students were memorizing the facts, the human anatomy and physiology, I approached medicine from a different point of view, i.e., from the prospective of a mathematician, running numbers and calculating probabilities. The more I learned about the complexities of human organs, such as eyes, the more puzzled I became when the numbers just didn’t add up. I learned that there are twice as many neurons in the human brain as there are stars in the Milky Way galaxy. The human eye was another masterwork of engineering, with billions of photoreceptors and neural connections. My mathematical calculations suggested that it wou
ld take trillions of trillions of years for organs that complex to evolve randomly, but the universe was presumed to have existed for less than fourteen billion years.

  I was thus nagged by the sheer improbability that life could form at random. But most scientists make no room for the possibility of God. The profession demands allegiance to positivism, the philosophy that only what can be tested actually exists. Scientists will argue that, in spite of its inherent complexity, the eye could still have evolved at random, even in such a short period of time. But I was shocked to discover that it actually took more “faith” for me to believe in random formation of the eye as such than to believe that perhaps some other force was at work. Life just appeared to be arranged far too well to not have been designed for an intended purpose.

  During my studies, I did an off-site rotation in which I shadowed a pediatric ophthalmologist named Dr. Stanley Hand, Jr. Our young patients in the local children’s hospital had congenital eye disorders, like cataracts and glaucoma. I told Dr. Hand about the research I was doing with Dr. Church, and how fascinated I was by the complexity of DNA replication and genetic disease. Dr. Hand and I talked about how many times the three billion base pairs of DNA in cells had to split and replicate during an embryo’s formation. As an embryo’s cells become tissues, organs, and limbs, there are so many opportunities for errors, even the slightest of which could result in significant congenital defects.

  “It’s amazing that anyone could come out of the womb normal and healthy,” I said as we walked through the corridor toward another patient’s room. “How is it even statistically possible that gestation is so orderly and complete?”

  At first, Dr. Hand gave me only scientific explanations for my constant inquiries. I continued to pepper him with questions, not just about biology and medicine, but about the underlying meaning of it all. Eventually he realized that I was searching for answers that wouldn’t be found in any textbook. I was on a quest for something bigger and deeper than science.

  “If human existence is accidental, then what’s the purpose?” I asked. “If the most complex living organisms on the planet are the result of random chance, how can life hold any meaning?”

  “I don’t believe that life is meaningless at all,” he finally said, “because I’m a Christian.”

  Up to this point, no one had introduced himself or herself to me as a Christian, and I was intrigued to find out what that meant. I had read about Christianity in the great literature of the West while I was in college back in China, but I hadn’t yet explored the tenets of the faith. All I knew at the time was that perhaps God did exist and possibly He was guiding my life. This sense of calling had continued to grow slowly and had crystallized throughout my years at Harvard. Perhaps Dr. Hand could finally help me find the answers I was seeking.

  One afternoon, Dr. Hand took me to lunch in the hospital cafeteria.

  “Do you see that car outside?” he asked, pointing through a nearby window to the parking lot outside.

  I nodded. “What is the difference between a car and a human brain?” he asked.

  “The human brain is infinitely more complex,” I said.

  “Do you think a random collection of scrap metal could assemble itself into a car?”

  “Of course not!”

  He leaned in, looking at me intently. “Then how about the human brain?”

  I was speechless. If a complicated machine like a car couldn’t create itself, how could I believe that an intricate organ like the human brain could? Even though the brain consisted of living tissue, both materials were made up of the same molecular pieces. At the level of atomic particles, there was no fundamental difference.

  “So, what’s the answer to all of this?” I asked. I had been baffled by the limitations of science, and I was ready to find more legitimate answers to the pressing questions about the nature and meaning of life.

  Dr. Hand gave me a Bible, and in the weeks and months that followed, I read it intently. It wasn’t clear at first whether or not I would find what I was searching for on its pages, but I was open to the possibility that it might hold answers that science hadn’t provided. The idea that life wasn’t fortuitous, that there was a Creator with a purpose for humanity, gave me great relief from all my confusion. The immortality and eternity of such a Being filled the void that science could not.

  I kept in touch with Dr. Hand for a while, but we eventually lost contact. Years later we met again at a Christian Ophthalmology Society meeting, and I told him how much he had impacted my life, and how my journey of faith had begun with the wisdom he had shared with me.

  Meanwhile, my experiments on E. coli DNA in Dr. Church’s lab only increased my conviction that there must be a cosmic, supernatural designer behind the complexity I witnessed under the microscope. As far as we knew, no one else was researching protein and DNA interaction inside a living cell. We soon discovered the fundamental difficulty that blocked the success of any such project, that is, the moment we lyse a cell, or break it open to inspect its contents, the interacting protein and DNA molecules are torn apart in the process. How could we then study the way these two components bind together inside a living cell if they came apart every time they were exposed? It seemed to be a scientific dead end, a logical impossibility. By then, however, my time with Dr. Hand had expanded my perspective to include the possibility of a solution beyond logic, and I was inspired not to give up just because I faced a scientific improbability. I trusted in a wisdom behind the cell’s design that was beyond what scientists presently understood.

  We persisted in our experiment and looked at the problem from several different perspectives. Eventually, we realized that perhaps one creative way to assess how protein and DNA interacted in a living cell was to look at a third component, namely methylase, an enzyme that patrolled DNA to protect and stabilize its structural integrity.

  We theorized that since the methylase enzyme constantly went back and forth over the whole DNA molecule, if any part of the DNA was not methylated, then that meant that perhaps there were proteins bound to that DNA region that were blocking the methylase’s access. We performed a series of experiments that searched the entire E. coli genome, and found out that there were indeed several dozen regions of DNA untouched by the methylase enzyme, suggesting that these could be the sites of protein-binding. I calculated that the probability of this result occurring by chance was one in 1,000.

  We wanted to double-check our theory that these unmethylated regions of DNA indeed represent regions bound by proteins, and thus are inaccessible to methylase. To do so, we used cells in which we knew that one of the biding proteins itself was absent, and we found that indeed the corresponding DNA region was now methylated, suggesting that the methylase enzyme now had unimpeded access to that DNA sequence since no protein factor bound there. It was another one-in-1,000 possibility that what we observed could happen by chance.

  Before long, the cumulative results of the experiments had pushed the statistical probability that what we observed could occur by chance to one in a million. We then reached the third and final stage of this groundbreaking project. If all our theories were correct so far, then there was one last test that would definitely confirm it. If we grew the cells in an environment that required a protein to bind to a DNA region, then the methylase enzyme should no longer be able to access that DNA region. We conducted that final experiment and indeed confirmed that finding, yielding yet another one in 1,000 chance that the observation could occur out of random! Therefore, the three stages of testing all confirmed that using methylase was an ingenious way to assess DNA-protein binding in a living cell. The final estimation of the cumulative probability that what we observed occurred by chance was one in 1,000,000,000, infinitesimally small.

  This chemical trinity of methylase, protein, and DNA was a true marvel of nature, an ultraprecise biological system whose parts interact in perfect synchrony. It was so beautiful in its complexity, so perfect in its coordination that I was now convin
ced this did not happen randomly at all, but rather by divine design. Dr. Hand was right; there had to be a Creator behind such intricate, complete, perfect designs that brought life to species from bacteria to human beings.

  Dr. Church and I had thus succeeded at developing a new method of studying DNA-protein interaction inside a living cell, a scientific achievement that I treasure to this day. Our discovery had wide-ranging implications for medical treatments, since researchers could use this methodology to study how genes were turned on and off in a living cell and how that led to disease. The paper we wrote about this new method was published in Nature, the most prestigious science journal in the world. Dr. Church and I were impressed at the publication’s impact—we received requests for copies of the paper from scientists in eighty nations. We were invited to present our findings at conferences around the world, and we applied for a U.S. patent through Harvard University. The research we did in Dr. Church’s lab was the beginning of many successful biomedical explorations I have undertaken throughout my career, each of which have not only excited me about the marvels of science, but more importantly, have revealed to me more and more of the glory of the Creator.

  * * *

  On June 6, 1991, my time at Harvard came to an end. That morning, nearly twenty thousand students, family members, professors, and alumni congregated in Harvard Yard. The university president gave the commencement address and conferred degrees upon students from both the undergraduate and graduate schools. Students were seated according to their schools, forming rows and rows of black and red graduation caps and gowns. The medical-student section was rowdy and fun. We blew up surgical gloves into five-fingered balloons, and when our school was announced, we tossed them into the air and watched them bounce throughout the audience. Adjacent to us were the law school graduate students, a much quieter and tamer bunch than we were. Among the law students was someone who, back then, was known as … Barry Obama.