Category: Dr. Curchoe’s Science


I pace back and forth, down the length of my bench and back to my computer again. My fingers steepled under my chin in the sort of pleading prayer that surely even an anthropologist from Mars could recognize. I glance at the email inbox lighting my computer screen, spin on my heel and walk back down the bench. Past the rows of glass bottles filled with the unguents and potions that I have been applying in various proportions to tissue meticulously harvested from various sources for the past two years. I rake my fingers through my hair and fidget with the collar of my white lab coat, which feels like a garrote right now. The email I have been waiting for sits in my inbox, poised for me to hit one button and with a quantized blur of zeroes and ones, the fate of years of my scientific work and my esteem as a scientist will be revealed. The jury is in, not only on the meager experiments that have consumed my every waking thought for the past two years but on the ten years of groundwork, laid by everyone from Nobel laureates to those who came through this lab before me.

I truly stand on the shoulders of giants and the responsibility of what I have done with their hypothesis lies heavily on my shoulders. As the first author on the paper, I am the one responsible for many of the experiments and for the interpretation of the data, which at this moment, has been judged very harshly in a process termed “peer review” by three experts in the field.

RETURN

Why can’t I do it? I am a woman of the Y generation, our motto being… Why wouldn’t/couldn’t /shouldn’t I? A woman my age can surely handle this just as deftly as we juggle work, family and social life. One other person knows the contents of this email, my advisor who has forwarded the missive to me. It is customary to first notify the last author on the list, who is termed the “corresponding author”. The corresponding author is usually the person who heads the lab and has procured the funds for the project. They will be there to account for you long after you have left to start your own lab. The other authors, the ones in the middle of the list, have contributed pieces of data, expertise on certain topics or valuable collaboration and will be the last to be notified. I take one more trip down the bench stripping away a tiny hangnail with my teeth, marveling at how I got to this point. The early stages of any project are fraught with excitement as one performs experiments all day in the hopes of resting easy on one piece of good news at night. Maybe you have finally calibrated that extraordinarily delicate instrument or maybe you have finally made the jump in the logical framework that leads you from your first piece of experimental data to the experiments that will build the bulk of your argument. When you return from work, weary at the end of a day that has been filled with squinting at the minutia of nature down the barrel of a microscope, you consume literature in vast quantities as if words themselves were enough to sustain your vital force. Making a comprehensive review of the work that has already been done can save you years of anguish simply by knowing what is not known.

The middle stages of a project are a vast flurry of data gathering. These are the nights that you simply cannot bring yourself to leave the lab and the couch in the break room starts to look appealing to you. The data is finally rolling in smoothly and you do not want to anger the PCR gods, so throw yourself on the altar of science as the sacrificial lamb and hope that it is good enough. With every fiber of your being dedicated to the data at this point you pray that your significant others can understand your fanatical devotion, and maybe even bring you a bite to eat once in awhile. Data can be a cruel mistress, seducing you into making fantastic claims. The thrill of knowing something that no one else does is heady and intoxicating. Emerging from the lab at the end of this stage leaves you in the confounding state of experiencing culture shock without having used your passport. Movies have come and gone through theatres, celebrities have gotten divorced or had babies, natural disasters have occurred in far flung lands and yes, the new president has been elected! What, you didn’t know? Enter the final stage, where the scientific imperative is on you to write so accurately about your work that anyone, anywhere, at any time can pick up your instructions and repeat your results. Luckily for me, the language of science, English, is my native tongue. The pressure to accurately transmit information across the communication gap is immense and it might occur to you that no one else in the family can make Great Aunt Sally’s apple brown betty quite like her. The normal gestation of a manuscript can be anywhere from two months to one year as you parse and prune each sentence into shape. Fish tales abound on this subject and every scientist knows a friend-of-a-friend who took either one day or fifteen years to write a manuscript.

Now you must also moonlight as an artist and as scientist-come-artist you have no formal training but you must paint your data into pictures pretty enough that they could tell the story of your work without the aid of words. The parlance of science is just as subjective as art and you are acutely aware that even DaVinci and Van Gogh have their critics. I sit down at my desk and take a deep breath to try to slow my irregular, pounding heartbeat. I am sitting in the exact spot where I have just spent the past several months incubating the document that I have sent to the people whose job it is to root out every logical flaw. To the scientist this is akin to sending your child on an errand on foot across the Autobahn. There is always someone who knows more than you do and the biggest fear is that one tiny initial flaw in reasoning has tumbled you down a steep slope into a logical wasteland, where everyone can see the forest but you, through the trees of your own data. Of course, you have aimed for a journal with an impact factor as high as you dare, hoping that this jury of your peers will find your work significant enough to accept for publication. Even if your work is deemed acceptable there will probably be suggestions of additional experiments you must do to satisfy all of the “what-ifs” before your work can be published. If your manuscript is rejected you will modify your impact factor expectations and submit to a “lower” journal to start the process of waiting and pacing again. I simply cannot wait any longer. I must know if my existence and scientific work has been validated. I steel my soul and click the button.

My day ends in a freezing microscope room in the basement of building 5 at 8:30 at night, starving for dinner, my attention riveted to the image before me as if it were finals week of American Idol.

I am one of the few people in the entire world that has been entrusted with the duty of tending human embryonic stem cells, which once formed the inner cell mass of a human embryo, capable of becoming an entire sentient being. A responsibility I do not take lightly. When my cells die for seemingly no reason or differentiate, as they are programmed to do into multiple cell types, I am staggered by the weight of my responsibility to maintain the sanctity of human life and the unique burden of proof I owe to the California tax payer who pay for my bread and shelter.

Everyday I come to work eager to solve a tiny problem that one day, like the power of raindrops to form rivers, may be combined with the discoveries of other researchers to potentially ameliorate the suffering of many thousands people.  The goal of my research is to coax human embryonic stem cells, the tabula rasa of cells, to become specific types of peripheral neurons. I have tried to convince the cells that this is within their best interest, without success, for many months. My strategy has been to simply recapitulate the timing of human embryonic development in a plastic dish in the lab. A deceptively simple task that would rely on nature’s own course, instead of the existing chemical or animal reagent heavy protocols, previously applied by research teams in Israel and Germany. This is a necessary step if the cells I am attempting to make are ever to be used for human cell replacement therapies. They must be cheap, abundant and made in a way that minimizes the risk of disease transfer across species.

A typical day in the lab consists of me feeding and watering my garden of stem cells. Once a week I transplant them to a new pot so that they have room to grow. I am a steward, benefactor, husbandry expert and teacher. I take some of the most gifted students each week and put them into special education classes. That is to say, I take a subset of particularly good-looking cells and suspend them in specific media that allows them to become neural progenitors. After five to ten days the cells are semi-specialized. They are like HVAC technicians, specialists in regulating the temperature of your home but incapable of hooking up the cable or wiring the spare room for light. They can now form any type of the thousand or so odd components of the nervous system but they can no longer form the cells of the liver, lungs or pancreas, for instance. My next task will be to ask them to become so specialized that they can only do one thing well. Many research teams across the world do this exact same thing but this is where we part ways. I have etched out my corner of the scientific playpen with the least sexy-est of neural subtypes, avoiding the stomping grounds of the immensely popular central nervous system. The neurons I hope to make will not cure Parkinson’s or Alzheimer’s or repair a severed spinal cord, instead they may one day replace any nerves outside of the brain and spinal cord that have been damaged, such as the nerves that provide us with touch, taste, sight, smell and hearing as well as a few others.

Recently, I have grown my neural progenitors on a lawn of complex substrate, a naturally occurring component of the developing embryo that peripheral neurons have been known to take a special liking to in vivo. I have fertilized them with a rich, loamy mixture of cytokines and growth factors, sugars and antioxidants. In theory, I can detect proteins specific to the type of neurons I am searching for with antibodies labeled in brilliant fluorescent colors: crimson, emerald and cerulean. I am searching for a protein aptly named Peripherin, an integral component of these specific cells discovered in 1982 by Madeleine Portier, Frangois Gros and colleagues, in the cells that I have grown under the new circumstances for two weeks. I start the two days long protocol with trepidation. Will my cells have accepted my guidance and graduated to become the mature neurons of the peripheral nervous system? If they have not been persuaded I will go back to the literature, searching for clues that have been provided by others studying the developing nervous systems of frogs, chickens and mice.

I finish the staining protocol, lovingly attach a coverslip to the glass slide, preserving the rare fluorescence I hope to observe and make the quick walk to the microscope room. Before I leave the lab I grab a hoodie and trade my flip-flops for socks and sneakers. I know from experience that the microscope room must be kept on the cool side to counteract the heat given off by the many mechanical calisthenics of those complex instruments.

I center my slide above the objective and fiddle with the focus knobs until the gray and white ghosts before me sharpen into the shape of cells.  I hold my breath as I switch from the white light to the UV light that will excite any fluorescent molecules that have stuck to my cells. Fine crimson filigrees of neural process extend before my eyes and I feel as elated and nervous as a new bride gazing through a veil of lace. Finally! My cells have willing done what was asked of them and I frantically snap the pictures that will be the proof of their existence. Dinner will wait.