Friday, April 07, 2006

Science.. What is it good for?

I still remember reading into biology books and getting very enticed and challenged whenever I would reach the end of a section describing an unknown function of a protein or a gene. I remember the way I used to eat up pathways and go through them in my head like reciting poetry. I remember the scientific discussions with the new comers and the fresh ideas about how to cure a disease or another. I remember the hopeful passages of significance we included in dissertations and proposals about a non-ventured route in drug development and a potential gold mine for therapeutics. I remember knowing all there is to know about the intricate cross talks and upstream and downstream regulators that lead to cancer. All what could go wrong and all what could fix it. I remember walking to the lab everyday going through the hospital, faces, shaved heads and little hopeful kids and I remember the vow we took to keep working and to make a difference. We wanted to make a difference and we believed that this is the ultimate selfless way to do it.

For years we were pupils of greatness, void of any self-interest. To us, this was the noble venue, far from being money-oriented and far from the glamour or the instant gratification of immediate care giving professions. Science was our salt and bread. It was what we lived for; it was our passion and existence. Part of us had the discipline to love science for the knowledge and the intrigue; we called them the NSH group. Others were NIH idealists, including myself, and we believed in funding for human’s sake. We did not care about funding for imaging spectroscopy of compositional maps of Saturn's moon Phoebe and we did not care about crystal trays of some gene in yeast that did not have human homology. We cared about money for human diseases. We cared about every penny and every minute of a researcher’s time and focus to go towards curing diseases. We could not bear looking at those ill faces while we stood useless and we would not stand for indifference. The idea of an AIDS vaccine not made available for people so that it won’t encourage teenagers to go and be wild with it and the funding cuts on the way to war, these were our battles and our issues. We had big dreams and we were rivals on the way to save humanity.

After a decade of science, I wonder what is left of our hopes and dreams. I wonder if P. still wants that private research facility. I wonder if the cuts on funding will persist in the post-Bush era. I wonder if people lost faith in us; that if we haven’t lost faith ourselves. Every now and then you are reminded of what you’re here for. Some people give you a feeling of importance and make you want to believe again, others through passive dismissal and hidden disapproval make you want to prove how great this profession is. Someone argued that one cannot compare the nobility of the medical profession to someone who goes to lab everyday based on the fact that doctors get an immediate satisfaction in making a difference. I am happy for this person to think that his job is the greatest of professions if this helps him perform better. But just for the sake of arguing, isn’t a nobler mission when you are making a huge difference in the life of the masses without even getting the slight recognition or monetary compensation? To each his own.

A recent significance passage from a proposal: In the last two decades an enormous effort has been produced to understand the biological and genetic bases of cancer, a progress fueled by both industry and government based research. Unfortunately, relatively few innovative therapies have been introduced in the clinics that proved to be more successful than or as powerful as available drugs. Drug development is certainly a difficult, time consuming process, and the success rates of new compounds that pass clinical trials is very low. This in turn slows down the appearance of new drugs that use innovative mechanisms of action to treat cancer. The bulk of modern chemotherapy is indeed still based on combination therapies that feature anti-mitotic drugs, like vinca alkaloids and taxanes, very effective molecules which target the function of the microtubule cytoskeleton. A major concern of these therapies is the development of resistance in some individuals and strong side effects which include neuropathies caused by the interference with microtubule function. In fact, I am exceptionally proud of my department chair who got the lifetime achievement award for introducing the use of taxanes into chemotherapy and who is still grounded enough to talk to me about hair dyes.

The use of anti-mitotic approaches is old fashioned now since mitosis, as we all know, is crucial in health as well for immunogenesis. The latest craze in research was apoptosis. The gold card in cancer therapy. Instead of inhibiting the cancer cells from dividing, which could affect the healthy cells, reactivate their controlled death. Brilliant, we all thought. Unfortunately though, and like most other phenomena, the amount of genes and proteins responsible for apoptosis would make your head spin too. BAK and BAD and BCL-1 and BCL-X and bim and dim and little tim and DIABLO (we started getting quirky with the names) and LAT and Syk and src and Fyn and FAK and rho and rac… names much as they are combinations for the alphabet and more. Proteins that cross talk in all possible ways. I remember my professor laughing when I asked how could a tumor suppressor be also an oncogene in response to the same stimulus and in the same cell line?

We went from that to cancer cell motility. If you can’t kill it and you can’t make it stop dividing, break its legs. Brilliant we thought. We want to disable breast adenocarcinoma from metastasizing. Keep on dreaming. Every pathway is different, at every time, at every subcellular location, in every cell line, within the same tumor, in each hand, in different labs and more. And even when a consensus is reached to the best fit of our best ability and best assessment, it will be different in vivo. Mice or rats and how old and what tumor. Is it the same in humans? Of course not and start again. And they still ask you, are we close to curing cancer? You want to say, the more we know the less we know and the less we hope, but it’s better to keep quiet. Asking me to cure cancer is like asking an underground rail road worker in Manhattan to build the infrastructure in Iraq and more. Cancers are like snowflakes in their uniqueness. Scientists find it to be fascinating and I think it’s fascinating that they do. My mom still doesn’t know what I exactly work on. So a drug that will kill tumors? No. a specific kind of tumors? No. A chemotherapeutic potential? No. What then? I work on understanding the localization of a specific protein, that is upregulated in some cancer cell lines some times, in response to a specific stimulus at a specific time under very rare conditions in vitro in a very specific cell line extracted from rats…

Maybe he’s right. Maybe P. quit. Maybe the age of big discoveries is long gone. Maybe we’re just nitpicking to keep the government money rolling to keep our doors open and people working. Maybe. Maybe science is good for nothing. Maybe Cancer won. An exquisite fascinating disease. An accumulation of minute mutations that is completely unique in every case and every human body. Maybe I don’t care anymore and that left me with nothing.

We say we’re godless and we only believe in science. Well guess who proved to be a bigger prick?

For better or worse though, it is who i am and it is what i do.


Fouad said...

Mirvat... did not finish reading your text last night. Just finished it this morning. For what it's worth, this should go to a journal, somewhere, I don't know where, send it out, indiscriminately, I won't attempt to praise it, it will be impossible to find the right words. Just send it for the world to read. There's just too few of us readers on here. Another thing, I am a firm believer that there is a silver bullit, we're just too ignorant to find it. Don't let little failures stop you, don't drown in the details, whether it will work in your hands or not, or in anybody's for that matter, nothing should take away the pleasure of doing it and trying. The biggest mistake I think we make in our life choices is to base them on the outcome rather than on the process. Now granted, a successful outcome is a wonderful thing, but the lack it of it, which is the case more often than not in such ambitious undertakings as defeating cancer, should not strip the process of experimentation and discovery from its beauty and the thrill that comes with it. Don't stop mirvat, don't give up on yourself. This is who you are, this is what you do, so enjoy it to the very fullest.

hashem said...

I'm not sure where to start. From the dreams I had myself, just like you, curing cancer, making people feel better, change the world....
Yes, these were big dreams. But guess what....everything starts with a dream....with a vision.
Getting to know things better, and maybe getting older as well, make us a little more realistic. More practical. But you'll always need that little excitement flame fueling your long and relentless quest. You have it, Mirvat, please keep it on....
You are a basic science researcher. god bless you because I know exactly what it means.
I went to medical school, but I worked for almost a year as a basic science researcher, in fact I had to...
To say that clinical medicine is more noble than basic science, is like saying using a machine, is more noble than building it. You may find new ways to operate it, new uses of it, but the machine has to have the capablities for that, and all dictated by what a smart designer, and thousands of poor workers put in it.
It's called the scientific method. It starts in the lab, with a question, a vision, and an idea, that gets a feasible experiment finding the right control(s) (oh...the controls....I still remember this part).
You get results....they need to be replicated, interpreted, verified, compared, prepared in a useful way, and then maybe, I stress maybe, get some use at bed side!!!
Not to mention here the frustration of a failed experiment, lost sample, the need to repeat and repeat....the long hours at the lab, waiting for the gel to transfer....
You still have people there in the lab, largely unrecognized, and underpaid, who are still excited about what they do, despite all these frustrations.....because each single, small success makes a big difference to add to a big and complicated picture as the one you described.
I'm sorry for being long in my comment, I just want you to know that alot of us at the bedside appreciate what you do ya Mirvat, and when I called for your help that day, it was because I had to choose between you, and the voodoo or this weird mixture of chinese mushroom with cilantro that a patient's sister mentioned as a potential treatment for cancer.
I can write pages here, but I finish here by saying we should never give up in this battle, you should never give up...
Hang on ya Mirvat, it's not that gloomy...

rouba said...

mirvat research is so important nowadays that you cannot be a doctor with a 'name' unless you're also a hotshot researcher. i think it is harder to go into a life of pure research than to go into clinical medicine because of the patience and perseverance you need to have in the lab, and the not so certain outcome of months/years of hard work. anyway, you cannot really compare the 2 professions because they're totally different, and P was not denigrating research at all, merely explaining why medicine is different. they are both equally important and one cannot be without the other at the present time-i probably wouldn't have gotten my position next year without telling them i want to do research for at least 6 months..

hashem said...

what position you got?

Ghassan said...

I agree that medical research and medicine, are connected but different. the academic world is sometimes oblivious to the actual realities behind disease (the stories that the doctors experienced in hospitals...)
But my question is what about people working on topics that are not related to human disease, some people are really interested in knowing more about a pump in the cilia of a paramecium. really. now this points out more the disconnect, and that researchers want to find out more about 'stuff' that might not interest regular people (or even benefit them).. and sometimes this is labeled as scientific curiosity, which medical doctors could only grasp when they understand how differently we think.

Mirvat said...

Fouad , thank you for your comment and you're absolutely right. sometimes along the way, during this very tedious process we go through, we get frustrated with the lack of results or progress that one would hope to achieve. i knew what i was getting into and i know how long the road will be. it's is the deal that comes with the immense satisfaction of being in a field that truly is directed towards making a difference. i just need to remind myself every now and then that just being in the process in an honor and that what will be will be..

hashem :) i hope we will never be out of ideas and solutions as to having to resort to voodoo. eventhough i've heard about a lot of cases where people renounce all medical treatment and resort to a strict spiritual regimen and show a lot of progress. i guess it's the power of our psychology.
i know that you grasp the concept of doing basic research very well and you understand how it is which always feels good hearing about. the controls:) i know. it is frustrating like hell and i like the machine analogy. don't worry we all feel like that every now and then. lose faith, lose attachment, lose ideas, but we always go back with a new excitment aand a new spark. thanks :)

Rouba, congrats for the position and i know i read P's second comment and it didn't sound as bad as the first. the 2 professions are completely different and cannot be compared. i don't like it though when somebody considers on profession to be better than any other and i kinda got this feeling from what he said. it doesn't matter anyway. that's the point right? to think our professions are the best so that we'll go on and do a great job.

and gus, there's all sorts of interest in the academic world. a lot of academic reseach goes straight to the bed side as you know and does not have the gap that others do. take carrasco or horowitz or zang on cancer and mcdonalds or sherer or whoever on diabetes. these are people whose reseach made it to clinical trials. but the other side, the extreme side i mean with people who study flagella , we had these discussions before. i never understood it but as long as we study ancient civilizations and the space and put all these resources into warfare development, we might as well study flagella and dwell on dicty..

FZ said...


I had to read your post twice because it felt so important and, like Fouad, i think it deserves as wide an audience as possible. meaning, life meaning, work meaning, spiritual meaning, global meaning, is such a tangle and so individual-- a personal construction, something you can't compare from one profession to another. I think I get a quasi-religious quiver (almost) thinking about it- because I believe God is in the details, however flagella-like, and to attempt to make sense of any detail in our universe, from a photograph of a tree to the sociology of urban schools to AIDS vaccines to the atmosphere of Mars, is an attempt to be conscious and engaged in what it means to be human, to try to untie a bit of the chaos. Maybe I'm a pessimistic-realist, but I don't believe in human omnipotence-- I believe that we should push to know, but I accept that we can't always know. That may seem too abstract, and maybe I'm a cynical doctor-- I guess I don't believe in silver bullets-- I believe in compromise, and trying to maximize quality of life rather than cowboy efforts at "cure," (although yes, cure is possible sometimes... but, um, maybe actually more rare than we think?) Maybe I've seen enough suffering and complications from medical interventions, and honestly, I think I would personally buy a one-way ticket to Fiji instead of choosing chemo if my breast cancer was advanced enough, not because I don't want to "fight," but because I wouldn't want to spend my last days in hospital corridors... I think the fact is that we can't always control the body as much as we would like to be able to. I have started to accept the power of the details... reading your blog, I was the struck by the beauty of what you describe-- and the sheer poetry of those gene names! as transcendent, however frustrating they must be at times. you inspire me, mirvat.

Mirvat said...

thanks fz. i'm more than happy with you guys reading what i write. and i'm very happy you liked the post. yes ironically enough those gene names could be poetic at times and the innumerable ways those proteins interact is fascinating. a never ending machinery that defines precision, a beautifully choreographed sequence of events that is unique in every way. the miracle of nature i suppose, we only need to look within ourselves to feel awed and to feel so small. i guess you have a feel of it to on the medical side. i do believe we need to push ourselves too, i do value humility being faced with what's so much bigger and better than us. and you're right, even when we don't have cures or work towards finding them, we make a lot of difference with the small steps we take towards enhancing the quality of life of a patient. that's where you guys make the real difference :). it's not pessimistic at all, it's the realistic view and assessment of the professionals who are on the other side of it.
and i think i would take a one way trip somewhere too faced with an illness like that.
we can't control the body and we can't control nature, including the diseases and the natural disasters and i always find it to be a nice reminder from some supreme power that we're only guests here. but while we are we might a well be good guests :)