Sunday, September 28, 2008

Depression as a Terminal Illness

Clinical depression is not just "feeling down." It's a debilitating illness, particularly when it becomes refractory to any treatment. Consider Dave Wallace's final days.

Maturation and Graduate School

I have thought extensively of last about what constitutes a person's "growth" during graduate school. If you have read any of my previous posts, you would imagine that a certain degree of cynicism is inevitable; frustration with experiments either working or not; and unique to the MD/PhD course, trying to remain faithful to the clinical aspects of our careers remains both a priority and dilemma. These are fairly concrete issues that have arisen, and their answers tend to be straightforward: work through the difficulty with experiments (adapt, invent, etc), accept cynicism but don't let it be your downfall, and try try try to get into the clinic once in a while (even if all the forces that be seem diametrically opposed to you in that quest).

I think there is something deeper that graduate research and training does, however. In my estimation, there are several areas in which the maturation we undergo in graduate school manifests.

If we consider the format of graduate training - let's say under the broad umbrella of any of the biomedical sciences - it's the first time in our lives (save for those who took any significant time off from school) that we have significant freedoms. Our schedule (save for a couple of classes) has very little structure. Our work day does not begin at 9 am or end at 5 pm. We don't have "required sessions," "small groups," "doctoring meetings," "preceptorships," "labs"; In many cases, we can take off from lab at a moment's notice if something comes up. We can work very hard or not at all. It really is up to each of us. This is quite a departure from the first two years of medical school as well as from undergraduate years. I'm not saying that during those periods there weren't different levels of engagement or attention (certainly there's a huge spectrum in college, and to a lesser degree medical school), but much of the responsibility and potential successes associated seemed built into the system. Rarely would a person finish undergraduate training early, and certainly not with medical school. And showing up for and doing well on exams (given at specified, pre-planned times) reflects on doing an appropriate amount of work in the time alloted. Graduate school, while having all the same features, seems wide open. Each day in lab - though part of a quest for finding and/or executing a thesis project - can be spent pushing the limit withe experiments; going just one more hour, finding time for one more set of experiments, staying a little later to make sure cells will be ready for the next day of work. As I have begun to find out, a willingness to "push harder" does make a difference. It takes a project from its very nascent stages to being well-developed and sufficient for a thesis. Don't get me wrong, I'm not saying this happens in one "magical" day, but if you pile on enough "push" days, progress is inevitable.

While the desire, and the willingness, to push hard - beyond fatigue, frustration, and failure - is certainly one of the pillars of graduate training, another important aspect that is unique to the training emerges. Many students who enter graduate science programs (and this is certainly the case with MD/PhD-MSTP training environments) have already developed an ability to execute experiments, analyze data, and write-up their results. Obviously, improving on this basic skill set becomes an essential component, but the next major hurdle is one I term to be Full Synthesis. In graduate school - if the training and product that results are satisfactory - then the ultimate goal is to be able to understand where research is at the present, propose a series of experiments, experimentally execute them, and then effectively interpret the results and propose new directions. Getting to this point, I think, is one of the most difficult leaps to make in all of our training; and while certainly we may not be proposing Nobel Prize-winning research in our first attempt at Full Synthesis, we can at least be faithful to the effort. I still struggle mightily with this, because the desire to piggy-back on the ideas of others or search for answers to questions we haven't really asked yet both become traps. I find myself at an interesting cross-roads in this sense. I'm working on a couple of inter-connected projects in the lab, and although I have a firm grasp of the experimental approach I am using and I know a good deal about data analysis, I have yet to really come up with "brilliant" new ideas either for how to analyze the data or craft new experiments to test ever-evolving hypotheses.

Don't get me wrong -- I'm not expecting for the goal of Full Synthesis to be achieved anytime soon. I know it is usually one that comes closer to the end (rather than the beginning) of graduate school; but I'm just saying that it builds in this frustrating tease - this notion that there's a level of intellectual engagement with our work, experimental and analytical command of our work, and an ability to see it all come together in the ultimate "Eureka!" moment. Maybe it will never feel like a "Eureka!" moment, and instead it will resemble something more of a "Duh!" Maybe. I don't think it really matters what the emotions are in the moment. What matters, I think, is that we honestly appraise our abilities now and that going forward we be willing to take on new challenges and responsibilities; we must learn (and dare) to "push" and "synthesize."

Wednesday, September 24, 2008

Nobel Laureates and Teachers

Today, I am joining a group of students having lunch with Nobel Laureate Erwin Neher. Dr. Neher won the 1991 Nobel Prize in Physiology or Medicine for his discovery of the patch clamp technique. The lunch discussion will no doubt provide titillating clues into the genius of Neher, his work over the years, and where he sees science going in the future. As someone who has been working on patch clamp experiments for the past three months or so, and as someone who sees how useful and revolutionary the technique is (and was), I stand in agreement with the thousands of scientists out there who marvel at his work over the years. He indeed contributes to science, medicine, academia, industry - to name a few areas - in innumerable ways. There's almost no debating the "greatness" of a person like Neher.

As I described my schedule for the day to someone this morning, she remarked, "Wow, that is so cool that you get to meet someone who has obviously done so much in the world; someone who's impact has been so immense." For whatever reason -- in part because this discussion was in the context of discussing topics in the first year of the medical school (described by some as "tutoring") -- that description instantly focused my attention on the role of teachers. Teachers spend their time - if they are college professors - doubling as researchers and lecturers/discussion leaders. In the high school or related setting, they focus primarily on introducing concepts, explaining difficult connections, and assessing student performance over time. But regardless of where teachers work and what exactly are their responsibilities, I think (and this certainly isn't a revolutionary idea) they can have an impact on the world that, much like work that warrants a Nobel prize, is not limited in its scope or seriousness.

If I had to choose three elements of my life that I credit with where I am today, I would choose 1) my parents, 2) my good fortune to live in the USA, and 3) my teachers over the years.

That is to say, it's hard to overstate the importance of teachers. Regardless of what I plan to do in the future, being a teacher -- in whatever capacity -- will be a part of my vocation.

I'm as impressed with a nobel laureate as I am with a game-changing teacher. I'll revise this post after the lunch to see if this sentiment holds up.

Update (4:00 P.M.): Sentiment holds up. Neher was great, everything I expected. And the teachers in my life continue to be up there with the Nobel laureates.

Friday, September 19, 2008

Friday in LA

It's a beautiful Friday, late summer/early fall kind of day. It's sunny, 82 degrees, with 34% humidity at 12:25 pm.

...and this is an average kind of west L.A. day.

A more substantive post to come.

Tuesday, September 16, 2008

Six Years

As Anthony's latest post ("Let's not insulate ourselves") hints, the Pomona community -- and indeed the world of literary scholars, readers, writers, and otherwise interested persons -- was beset this past weekend with unspeakable tragedy. We lost the writer of a generation and a teacher of profound meaning to his students.

I write not to reflect on Dave Wallace; I never studied with him, and I have no unique insights to share. While he inspired me, in many ways, to continue to write after entering the MSTP at UCLA, I can't speak to who DFW was as a person. And so I won't try to reminisce or eulogize. But I have some thoughts on death, dying, grief, and how they don't simply bespeak unimaginable tragedy. They - in sum total - offer us some clues into the human experience: the very act of living.

Six years ago today - two weeks into my freshman year of college - a good friend of mine (fellow musician, tennis player, serious student of science and math) was killed in an automobile accident. He was a man of immense promise, who, in his first few days of college was plucked from the earth.

I can remember the entire sequence of events immediately after his death in chilling detail. The message from my roommate. The frantic phone calls. The confusion: was he still alive? Where was he? He's gone? Oh, my god.

The reality: the tears, the shock, the horror. I remember my friend and sister picking me up from Pomona, the drive home to South Pasadena. The vigil at the High School. I remember then staying stoic for an entire week - between the shocking revelation of his death and his memorial service - and then in an instant succumbing to overwhelming emotion. I recall playing the violin for my friend, a musical ode to a fallen artist.

Another week passed. And then I returned home again - two weeks after he had died - this time to see my friend committed to eternity in the ground below.

To return to the sequence of these events still shakes me to the core. Here I was, all of 19 years old, in the midst of the newness of college, and my friend was dead. Certainly, the rest of his friends and I faced an immense collective loss; but my own mortality was suddenly in the forefront of my mind.

As the young (and the old) tend to do, I spent the days, weeks, and months pondering my own life. What would happen if, in a split second, my life were to end? What kind of mark would I have made, and (perhaps most importantly to me at the time) how would people remember me? I recall thinking about this question frequently when walking across the quad at Pomona, during long runs, and sometimes after an evening of drinking as I faded off to sleep. I (and indeed many of my friends) felt robbed - we were robbed of a good human being, a person who made us laugh, smile, and wonder what he would do next; and we were robbed of our innocence and invincibility. Just when we were beginning to gain our intellectual footing on life, and when our minds and bodies were starting to reach unison in their maturity, our new-found stability and confidence was shattered.

Death was indeed difficult for me to swallow. While of course initially it was a question of justice - just how "wrong" it all was - that was just the first stage. Eventually, I returned to reality and could easily note the world is devoid of justice for millions upon millions of persons. The next step was fragility. Could I be next? Just as with the injustice in the world, I too learned to live with the fragility of life. Next was the live life to the fullest ethos so many people talk about. Again, while this seemed an impossible creed to follow, I soon realized that living life to the fullest was just another expression for authenticity. And who the hell can claim that he really ever reaches total and perfect authenticity? (To this day, it is, like total nirvana, an admirable but unattainable goal).

I guess as that first year began to pass, I gradually turned the corner with my grief. (In fairness, I cannot imagine, and in fact know, that this was not the case for his family. For parents, the overwhelming grief that accompanies the loss of a child is thought to last at least five years before any sense of normalcy can be possibly achieved.) For me, the year ushered in a gradual weathering of my temperament. I was a little bit more introspective, and little less worried about how I looked or what I was doing, and my journeys were a little more personal. Of course, this all seemed to be somewhat at the expense of my social connections during year one at Pomona. (Somehow I was a little disconnected from everyone else, and it wasn't until my third year that a core group of friends would be established.)

In that first year, there were hints that, in spite of the indescribable feeling of loss, I was becoming liberated from some of the innocence of life. This indeed sounds like a contradiction-in-terms. But I think that by going to the dark place of death -- seeing your friend lying in state just a month after he was vibrant, alive -- while staying engaged in life, I began to relish in the act of living. Of course I still wept for my friend. I weep several times a year when I remember him - I wept today for a few moments. But I also love the life I am living and the life that I am capable of living. It's not just a sense of "you never know how long you have to live" kind of feeling that drives this. It is the idea that, in the face of grief and sadness, happiness and ecstasy, or anything in the middle, there is a vital energy we all possess. It's an energy my friend had - it was this energy that drove me to weep for him; but it is also an energy that made me look inward. It made me acknowledge the fragility of my life, reassess the impact of my actions, and my relationships with others. It helped me to love others more fully and gladly, and it in turn made me less afraid to talk about my love for others and express it genuinely.

I still don't think I understand anything better; let's just be clear on that. After all, understanding such questions as "When is it our time?", "What is it like in death?", "What is a meaningful life?" are impossible to answer. I guess realizing that, and accepting the somber reality of death in the presence of our lives, makes the act of living less burdensome. We cannot - in our human existence as it stands - truly understand the nature of questions that science, medicine, philosophy, politics, literature, history, and mathematics have never been (and never will be) able to answer.

But, I do think our minds can evolve - our perspective can become richer and the context in which we ask these questions is capable of generous expansion. As evidence of the Epiphany-in-progress that is life, I recently had a dream about my friend. In it, I swear the premise was that he had never left. I couldn't touch him, and we had non-verbal conversations (almost telepathic, I guess), but he had not left. As I tried to make some meaning out of the dream, I reasoned that this all came back to the "energy" of my friend. Both his energy and my energy come from the same divine elements of the universe. And maybe, just maybe, what happened six years ago has helped me to begin to realize that the very energy that makes us unique (and what makes us grieve for our fallen comrades) is energy indivisible from our own. It forever binds us to them, and them to us. It keeps them in our dreams, and transforms our lives. And it is ubiquitous and limitless in our world--it sets us free.

The (unfulfilled) promise of personalized medicine

This recent piece in the NY times outlines one of the current follies in biomedical research. The idea -- sift the human genome and find common, widespread variations that explain some of the most common diseases -- sounded great; in fact, it was downright sexy. But one researcher thinks that's a bunch of rubbish, and that the current (and very expensive) approach isn't working. And some of his rationale is rooted in the logic of rigorous genetic and evolutionary theory.

Not to sound cynical or say "I told you so," but personalized genomic medicine sure sounds a lot like a science project for which many of its conclusions (we'll know what causes X cancer and Y vascular disease) would be highly anticipated at the start of the study.

At any rate, this is food for thought, and we invite the discussion to continue in the "comments" section below.

(Plus, the article is an interesting look into a scientist who has blended population genetics with, in my best estimation, anthropology...)

Sunday, September 14, 2008

Fooling everyone, including ourselves

Science is mighty clever. For a discipline that prides itself in having objectivity and brutal honesty, Science has a lot of dirty little secrets.

Consider news reports that come out -- "Scientists discover X may be linked to Y!" -- and instantly a series of articles state the seemingly indisputable claims that accompany the headlines. Famous researchers go on TV programs, touting the revolutionary results they have obtained, and people marvel at the progress and excitement such work generates.

Beneath the surface, however, is something far more sinister. I will say, and object as you wish (please comment as you see fit) that many of these Amazing Discoveries were a foregone conclusion even before the experiments were done. The answer has a lot to do with the National Institutes of Health (NIH).

Consider how the NIH gives out funding -- it requires that researchers have interesting questions, capable of extensive investigation. Of course they also require that a huge opus of work has already been done on a topic. In so many cases, the finished product is close in sight, and the $1 million + of an RO1 grant rewards the background work much more than it motivates researchers to uncover new, surprising, shocking findings. Being bold - trying outlandish experiments - requires the all-too-rare funding from the Howard Hughes Medical Institute, or from small "seed grants" from the NIH. I don't propose how this gets fixed, but I see a problem in how hard it is to be bold.

I recall a conversation I had with a research mentor early in my training during my undergraduate days at Pomona. I complained that, because I wasn't clear what the point of my research was in a particular area (I was attempting to look at oxygen toxicity in obligate, anaerobic hyperthermophiles - you can understand the contradiction in terms), I probably wouldn't see meaningful results. He explained, "It's easy to obtain and publish results when you know what you're looking for. It's much harder (and braver) to ask questions that no one has ever asked before and then attempt to make sense of experimental results...such results have no real context, but that's real science." I think I understood his point -- the real richness of science is in the truly uncharted, the rarefied air, the untasted vintage. But is such risk-taking conducive to the present world, where we are so pressed for time and money? That I cannot answer. And yet I suspect the scientists who really "get it" (the nobel laureates, the inventors, the pioneers) probably think that there is no other way to do science in spite of every imaginable obstacle convincing them they need not be bold. Maybe.

Returning to the concept of "clarity v. opacity," I think I can claim clarity on one issue: I refuse to submit to a career in either science or medicine where I cannot be bold in my approach and vision. I won't just sit in a lab, with a series of predictable and interesting projects and RO1s to get funded. I refuse. I won't just sit in the hospital or clinic and see patients every day without some sense of adventure or risk-taking. I don't want to do "translational" research if all it means is that target X that we study is related to disease Y. That's not translational. It's correlative and it's pandering. It's like saying, "Well since LA is next to Mexico, everyone who lives in LA has foreign policy experience." Translational research, for which I have a passion, must transcend the traditional boundaries of science and medicine. It must have an infinite growth mindset. It can't just answer the associative question of, "is this applicable to that?"

Research, for me, has to be bold: for it to survive in my restless soul, it must ask new and unheard-of questions. It must, or I will find another way to channel my creativity. Because writing RO1s, sitting in a lab, and pondering how to squeeze more money out of the NIH is not my idea of a career. It's just a less lucrative way of selling out.

Let’s not insulate ourselves

It has been a while since I last wrote on this blog. The reason is silly: I have been expecting significance, a greater meaning from my posts. So here I go:

I am five weeks deep into medical school. The five weeks have been fine. Medical school is medical school. Nothing incredible, nothing amazing, nothing horrible. It has its pros and cons, just like any other program. But I am not writing to rant or rave about my education. Not yet. I am writing to let something out. Bear with me, please, as I struggle with some thoughts.


America is supposed to be a country of ideas, a country where ideas rule, where reason wins. Sometimes the ideas are wrong, propagating a wave of –ists that we are more than ready to forget. The compassionate American will recognize the problems and face them, address them, and challenge them.

I knew a compassionate American. To me he was a teacher, a role-model, an inspiration. I admired the way he used his words to explore what it means to be human, what it means to be an American, living the fuck-ed-ness of our society. He explored lines of thought that the average American prefers to seal off, pretending they do not exist, under the cover of our flag.

This compassionate American hanged himself two days ago. Am I disappointed? Yes. What will I do? Try to be compassionate. Ideas live on, as long as we want them to, right?