Respectful Insolence

Jake over at Pure Pedantry pointed the way to an article in Science that I hadn’t seen yet because of my absence. Just like yesterday’s topic, this one too is right up my alley. Specifically, it’s about something near and dear to my heart, namely the trials and tribulations of being a physician-scientist. The article paints a rather grim picture, with the observation that, although most MD/PhD’s would like to remain researchers, many are dropping out in order to become straight clinicians, clinical instructors at medical schools, or industry researchers. Jake’s commentary is certainly worth reading, and I agree with much of it; however, given that I’m where Jake would (hopefully) like to be in 15 years or so, namely an MD/PhD with an independently funded lab and who still takes care of patients, I thought my perspective on the article and its topics would complement his.

My perspective is different from Jake’s in that he has not finished his training or even entered residency yet. I, on the other hand, have not only finished MD and PhD training, but have gone through residency and fellowship and am early in the third year of my first five year NIH R01 grant, the “gold standard” grant to which nearly all biomedical researchers aspire. Moreover, it should be noted that I did not come to my position in the more “conventional” manner of a combined MD/PhD program that is the rage these days. Believe it or not, when I applied to the MD/PhD program at the University of Michigan, my application was rejected. Oh, they were more than willing ot let me do the program if I paid my own way (the application was, more than anything else, for spots that were paid for by training grants), but I couldn’t afford to do that. Consequently, I simply went to medical school. Then, after my second year of general surgery residency, an opportunity presented itself to take a break and go to graduate school, and that’s just what I did, returning to complete my general surgery residency after I got my PhD and then going on to do a research fellowship in surgical oncology. It was a long, hard road. I was almost 37 before I got my first “real” job. But I was about as prepared as I could expect to be to start my own lab.

So far, I’m doing quite well. Indeed, surgeons with NIH R01 grants are fairly rare birds. However, I must note that I got my first R01 just before the NIH funding climate turned so sour. Indeed, I basically slipped in under the window, as the grant application that has funded my lab since 2005 would not have been funded had I submitted it this year. This knowledge leaves me with a profound sense of uncertainty as I rapidly approach my next big milestone: Renewing the R01 for another five years. Although my lab has been productive, like most investigators in my position, I have grave doubts about whether I’ve been productive enough or published enough. However, in a way, that’s just whining. I really feel for physician-scientists who have just gotten their first faculty position and are expected to obtain NIH funding in this current climate. Their situation is far more dire than mine.

In fact, this Science article captures the essence of the problems facing young physician-scientists:

If scientific discoveries are going to lead to treatments for patients, physicians trained to understand and do research must play a central role. After many years of decline, the number of physician-scientists available to do that work has begun to recover thanks to several new programs for recruiting and retaining talented students, according to an article published in the July issue of Academic Medicine.

But can young physician-scientists succeed in building and sustaining the research careers that they hope for during their lengthy training? The difficulties they face are so severe that many abandon the effort, says an article by four experienced physician-investigators published in the February issue of Gastroenterology. The departure of so much young talent constitutes nothing less than “the burning of American intellectual capital,” lead author Mark Donowitz of Johns Hopkins University in Baltimore, Maryland, told Science Careers in an interview.

The nearly 500 students enrolled in M.D./Ph.D. programs at 15 universities who answered a survey about their experiences and plans for the Academic Medicine article have a strong interest in becoming researchers. The majority anticipates careers primarily devoted to basic research, with many of the rest intending to focus on clinical or epidemiological research. More than 90% of the respondents want to work at academic centers.

This makes perfect sense, of course. After all, why on earth would anyone go through the torture that it takes to get an MD/PhD if he or she didn’t want to do research and be in academia? The reason that I went to the trouble to get a PhD, for instance, is because I did not think that my training in science was adequate to be a true translational researcher, who could, to cite a cliche, translate basic science findings from the “bench to the bedside.” I was correct. The training in the scientific method that came from my PhD studies was just what I needed.

One thing that the article gets right is that it is probably not the pay differential between academia and private practice. True, I was grossly underpaid when I first started ou. However, thanks to mandatory yearly pay increases for me (the joy of working for the state!) and declining reimbursements putting the squeeze on private practice surgeons, over the eight years of my career thus far my pay has increased to the point where the pay differential between what I make now and what I could make in private practice has decreased from well over 100% to probably around 30% or so. Nor is it the inherent difficulty of combining a career in research with a career in clinical medicine. And, make no mistake about it, it is very, very hard indeed to combine the two and be effective at both. I knew what I was getting into, as much as it is possible ever to know based on the experiences of residency, graduate school, and fellowship.

No, it is the structure of academic medicine that is the problem. As I’ve discussed in depth before, we are in essence free lance operators, not unlike the situation that some used care salesmen find themselves in. the university gives us a “startup package” and then expects us to become self-supporting through obtaining NIH and other grant funding within 3-5 years. We are expected to fund a high percentage of our academic salary (the NIH will not pay for the clinical part of our salary) and fund our research entirely through grants. This works reasonably well when it is not too difficult to obtain external funding. However, in today’s climate, where in my field (cancer) the NIH is funding only around 10-12% of grant applications, its flaws manifest themselves. Even excellent grant proposals do not achieve funding, and even excellent researchers cannot support their laboratories. As the article puts it:

The problem… stems from the fact that every lab chief “essentially is running a small business.” Like all businesses, “you have to pay your bills.” Lab chiefs, however, can only get the money they need by winning grants, which today’s tight funding and intense competition make unpredictable and unreliable. “You get them for a few years, then you lose them for a year, then you get them again. Consequently, people are continually essentially going bankrupt,” Donowitz says.

But unlike ordinary businesses that can use capital reserves to keep the doors open through hard times, government-funded researchers cannot save up for lean years. The rules decree that “at the end of the year, you can’t carry over more than 25% of what they give you. The grants are quite small, so you cannot weather a downturn,” Donowitz continues.

I haven’t “gone bankrupt” yet, but it could well happen in 2010, when my grants expire, if I cannot compete successfully to renew them. My failure would not necessarily mean that I’m a bad scientist, either. Better investigators than I have failed to renew their first R01. A lot will depend on whether the funding climate has improved and how productive I can be in the next two years or so.

Of course, as is pointed out, the key difference between physician-researchers and pure PhD researchers is this:

Unlike Ph.D. researchers, medical doctors can always make a living by hanging out their shingles. “But that’s not what this group of people wants to do,” Donowitz says. The substantial earnings gap separating research and practice is not an important factor in young physician-scientists’ decisions to leave the lab, he believes. “There are a bunch of us who are not interested in making this extra money but are turned on by the thought process of doing science. … The money is really, I’m convinced, not the major issue at all.”

Instead, “lack of security” drives physician-scientists from research, he says. “You’re always at risk of going bankrupt”–not personally, he emphasizes, but as a productive investigator. Anxiety and uncertainty produce “a very difficult life.” As proof that stress and discouragement, not lack of love for science, lead physicians to quit, Donowitz notes that “the people who drop out of science generally don’t leave the academic center. They become the clinician-teachers.”

That is one of the biggest advantages of being a physician-scientist. If a basic scientist fails to obtain funding before being tenured, he’ll be out of a job, after which his options will not be appealing. He can either go into industry, try to find another tenure-track academic position (not easy after a track record of failing to be funded once), disappear into the twilight world of the poorly paid and unrespected adjunct faculty, or take a job in academia as a laboratory manager, thus becoming utterly dependent on the grant support of the principal investigator for whom he works. A clinician has much better options if he fails to be funded, thus making it far easier simply to “drop out” of research if the going gets tough. Indeed, I’ve been told by more than one person never to give up clinical practice, because I can always make a living operating if this whole research thing doesn’t work out and a number of clinician-scientists weather downturns in grant funding by doing just that. Were I ever to fail to renew my grants and thus lose my laboratory, that is probably what I would do, although I would view it as a professional failure of the highest order, whether that characterization would be fair or not. Even so, I’d still want to remain in academia, perhaps doing clinical research and teaching.

So what’s the answer?

As always, it’s a question of money and commitment? Jake is correct in asking whether we’re willing to put our money where our mouth is by providing sufficient funding to allow the MD/PhD researchers in whom we’ve already invested to have a fighting chance to compete for independent funding and develop actual independent research programs. I’m less sanguine about his (and the article’s) suggestion that more flexibility in carrying over unspent funds to help researchers survive downturns in funding, given that such a solution would be a stopgap at best and only delay the day of reckoning by at most a year. The current boom-and-bust system that allowed as many as 30% of NIH grant applications to be funded in the early 2000s could obviously not be sustained, happening as it did in the context of a five year plan to double the NIH budget. The problem is that the return to reality has been far quicker and more painful than expected, anything but the “soft landing” envisioned by the NIH leadership near the end of the doubling period in 2003. If we are to sustain a high quality research programs that produce the most rapid translation of basic science findings to clinical treatments, we have to provide enough funding to allow MD/PhD researchers to sustain their laboratory efforts and be sure that we are not producing more MD/PhDs than we are willing to support.

Even so, would I do it again? The answer is: Probably. I really do believe in the value of the combined MD/PhD. Few MDs have the scientific rigor that allows truly great research to be done. Those who do almost invariably acquired it through research experience comparable to at least one rigorous postdoctoral fellowship, if not more. In addition, essentially zero PhDs whom I know have the practical understanding of human disease to be able to identify what are the true deficiencies in our knowledge of the pathogenesis of individual diseases and our ability to diagnose and treat it. They can’t really know because they’ve never taken care of a patient. Moreover, physicians have more of a sense of urgency; we see the results of the deficiencies of our treatments every day in patients whom we cannot cure or even treat well. Given all this, I am indeed heartened to see that there are more students becoming MD/PhDs. However, it is depressing to think about how many of them will become and remain productive translational researchers once their training is complete.

Comments

  1. #1 vlad
    September 11, 2007

    “I was almost 37 before I got my first “real” job” I was ticked about starting my career at 27 kind of puts my experience into perspective. I have friends in the PhD programs who are really hurting for funds. Good luck to all researches, we’d be really screwed with out all of you.

  2. #2 bob
    September 11, 2007

    Do you think it is dependent on research area? As a broad field I was always under the impression that oncology/NCI was one of the more grant-friendly fields because the “cancer cure” is always a good sales line. If oncology is this bad I can’t imagine how it is for hardcore barely-clinical basic science.

  3. #3 JP
    September 12, 2007

    Ouch. This is a sorry contrast to my field, electrical engineering. Funding is still a hard-fought game, but a thriving industry provides more than enough for truly promising research.

  4. #4 Drugmonkey
    September 12, 2007

    “In addition, essentially zero PhDs whom I know have the practical understanding of human disease to be able to identify what are the true deficiencies in our knowledge of the pathogenesis of individual diseases and our ability to diagnose and treat it. They can’t really know because they’ve never taken care of a patient.”

    essentially zero, eh? that is complete and utter crap. really. I call the most emphatic bullshit.

    so by this rationale, we have made no progress whatsoever on any “human disease” that is not guided by MDs who have the ability to identify “true deficiencies”, right? please.

    how do you view all the PhDs who conduct research on human subject populations, even if they are not tasked with giving direct care? you think they don’t know anything about the deficiencies in our knowledge? With the brain disorders (my frame of reference) from Alzheimer’s to schizophrenia to substance abuse I’d put the top nonMD clinical researchers knowledge of what is important to pursue up against any MDs’ knowledge any day.

    The funny thing is, that you mention that MDs aren’t generally prepared to do science before postdoc type training. true. the two prime reasons are first the training as an authority culture (“my view has primacy because of my credentials”, rather than “my view has primacy because of my data-backed rationale”) and second the myopia of arguing from the anecdotes of patient care. Yet these seem to be the traits you are also criticizing PhDs for not expressing…

  5. #5 psychepi
    September 12, 2007

    I have to agree whole heartedly with drugmonkey. As a non-MD PhD researcher (epidemiologist) working in academia. When sound scientific or methodological prinicipals collide with my clinician/researcher colleagues “clinical experience” I am consistently dismissed simply because i am not out there in the trenches. Oddly, though, its very rare that I don’t understand the clinical problem we are trying to better understand while my clinical colleagues fail to grasp basic principals of good research methodology. Standard medical training that places a premium on confidence in ones decisiveness is actually pretty antithetical to the scientific inquiry. I wouldn’t generalize to all clinical researchers from this blog, though. Anyone devoting such effort to publishing their every thought is bound to be a bit more arrogant than your average MD. In fact, if he were one of the junior faculty in my lab I might suggest that the “blog” time be used more effectively on research.

  6. #6 Orac
    September 12, 2007

    &ot

    In fact, if he were one of the junior faculty in my lab I might suggest that the “blog; time be used more effectively on research.

    Then it’s a good thing I’m no longer junior faculty and have been PI on multiple grants, including D.O.D., NIH, and private foundations, my main sources of funding right now being an R01 and a large foundation grant. (Next stop, PI on a P01, I hope!) That gives me the luxury of telling you quite bluntly that how I allocate my time and what I do outside the clinic and lab is none of your concern Indeed, were I junior faculty in your lab, I’d tell you the same thing–and you would have had no complaints about my lab work, either. I’ve never given any PI for whom I’ve worked reason to complain about the quality or quantity of my effort in the lab or in my understanding of the science and literature relevant to whatever projects were going on in the lab.

    As for my comments, it’s not about “arrogance” (although it does take a certain confidence that may or may not be arrogance to cut into someone for therapeutic effect). For example, I always show the utmost deference to what my statistician and epidemiologics colleagues tell me as far as rigorous study design and try to follow their advice as closely as possible. However, for many diseases, it’s simply not possible to understand what is and what is not an important question if you don’t take care of patients, any more than it would be possible for me to understand the molecular biology behind various cancers as well as I do if I had not gone through the PhD program (maybe some MDs could manage it, but I couldn’t) or serious statistics without taking serious training in statistics. I’m sorry if it pisses you off to hear it, but it’s true. If you want to swap stories about cluelessness, I could easily point out how many times PhDs have approached me or one of my surgical colleagues just to get tissue and couldn’t understand when told that the question they were looking at was irrelevant to patient care. I could also swap stories of arrogant PhDs who view us surgeons as nothing more than technicians to provide them with human tissue to study.

    The bottom line is that MDs and non-MDs bring distinct knowledge and skill sets, neither of which are entirely adequate for a full understanding of disease. MD/PhDs come about as close as any single person can to bridging the gap and straddling both worlds (and I don’t claim that we can do that other than in our own relatively narrow areas of specialization and interest). That’s why they’re valuable in translational research, and that’s why it’s disheartening to see so many of them dropping out of basic research.

  7. #7 Orac
    September 12, 2007

    essentially zero, eh? that is complete and utter crap. really. I call the most emphatic bullshit.

    […]

    how do you view all the PhDs who conduct research on human subject populations, even if they are not tasked with giving direct care? you think they don’t know anything about the deficiencies in our knowledge? With the brain disorders (my frame of reference) from Alzheimer’s to schizophrenia to substance abuse I’d put the top nonMD clinical researchers knowledge of what is important to pursue up against any MDs’ knowledge any day.

    Jumpin’ Jesus on a pogostick, you’re flagrantly attacking an obvious straw man.

    I said that essentially zero PhDs have PRACTICAL knowledge of the deficiencies in our understanding of treatment and disease because they do not personally treat disease themselves. They don’t know the practicalities of what works and what doesn’t, what tests are good, how they could be made better. In other words, they don’t have that “in the trenches” knowledge of what clinical questions are truly important and which ones are not or, on a more mundane level, the difficulties and practicalities of administering various therapies. They may think they do, but all but a very few of them don’t, just as many MDs think they understand the molecular mechanisms behind various diseases but all but a very few of them in actuality do not. Many are the times that I’ve had to gently explain to various PhDs that the questions they think important about a particular disease are not really of much consequence “in the trenches,” just as probably an equal number of times I’ve had PhDs patiently (or not-so-patiently) explain to me how my understanding of various molecular pathways is deficient. Maybe the situation is different in the neurosciences (and, now that I note that the only two PhDs who have taken me to task for my characterization appear to do research in the neurosciences, it may very well be, given that many psychologists do deal with patients), but for cancer, GI, and cardiovascular medicine, fields in which I’ve done research, I stand by my characterization. Moreover, it’s also true that clinicians bring a sense of urgency to the research, given that they face the deficiencies of our present management of diseases every day and PhDs usually do not. As I said before, it’s about different knowledge and skill sets brought to the table by each discipllne and MD/PhDs coming as close as humanly possible to straddling both worlds.

    I will admit that perhaps I could have phrased it better. Perhaps the phrase “true understanding” was poorly chosen, but the word “practical” was certainly not, nor is “in the trenches.”

  8. #8 Dale
    September 13, 2007

    In addition, essentially zero PhDs whom I know have the practical understanding of human disease to be able to identify what are the true deficiencies in our knowledge of the pathogenesis of individual diseases and our ability to diagnose and treat it. They can’t really know because they’ve never taken care of a patient.

    Coming late with another non-MD comment. I might give you the deficiencies in diagnosis and treatment but the deficiencies in knowledge of the pathogenesis? For that I’d like to see some hard data, rather than anecdotal comments.

    As far as the comment that Ph.D.s can’t know because they’ve never taken care of a patient … I’m reminded of comments made by those who claim that neither doctors nor researchers can really ‘know’ about a disease or the efficacy of an ‘alternative treatment’ because they’ve never suffered from the disease nor tried and found relief in the treatment. If I buy your argument about MD/PhDs versus Ph.Ds, don’t I have to buy theirs about who is qualified to judge treatment efficacy as well?

  9. #9 Orac
    September 13, 2007

    If I buy your argument about MD/PhDs versus Ph.Ds, don’t I have to buy theirs about who is qualified to judge treatment efficacy as well?

    No, because both MDs and PhDs (and MD/PhDs, for that matter) approach disease and patient care from a scientific world view, using a common scientific understanding and considerable overlap in methodology. Such investigators may differ in the knowledge and skill sets that they bring to the task of finding better treatments, such that neither alone can usually have a full understanding, but they nonetheless operate from a similar world view.

    Alternative medicine practitioners in general do not operate from a scientific understanding of disease, and their “understanding” is generally vastly different from that of “conventional” researcher. Moreover, although MDs and PhDs (and MD/PhDs) may deceive themselves over how much they know, but their self-deception is not prone to the same major biases that most commonly deceive alternative practitioners and their patients, biases such as the placebo effect, regression to the mean, etc., which are the sorts of things that lead them to be deceived into thinking that their woo is working.

    In other words, you’re comparing apples and oranges.

  10. #10 Dale
    September 13, 2007

    The point I was trying to make Orac is what is your evidence (as opposed to opinion) that physicians are better equipped to study human disease than are Ph.Ds? I would note, for example, that the majority of Nobel prizes for Physiology or Medicine awarded since 2001 have gone to Ph.Ds, not M.D.s.

  11. #11 kt
    September 15, 2007

    As you must know, the structural issues you write about are not specific to academic medicine – they are a part of academic science in general. The expectation is that the majority of one’s salary will be derived from research funds. It’s typical for pure scientists in biomedical fields (particularly at medical schools) to get between 50-80% of their salaries from their own grants. What is unique to the MD/PhD situation, as you point out, is that clinical income can always be used to make up the difference when research monies are tight, and so there is (in many departments) pressure to take on more clinical duties at the expense of research time.

    Allowing researchers to retain a bigger slush fund to tide them over in lean years will not alleviate funding problems that scientists are presently facing. These do stem from structural problems, but not at the university level – they lie in the myopic granting structure of the NIH, vividly illustrated by the recent doubling period. There’s too much money that goes toward training grants – this ensures that every boom period will be followed by a bust, as the supply of trainees grows, while the number of permanent research positions stagnates. Not a novel observation, but still true. I suspect that only a wholesale change in NIH granting priorities would remedy this – for instance, awarding fewer institutional training grants, and smaller but more numerous R01 type grants. In some ways this is happening de facto, as universities have slowly started creating bridging research positions for young scientists – they provide autonomous PI status and research space for starting a (very) small research group.

    Finally, I’m always a bit nonplussed by articles like the Science piece that sparked your post. These calls for increased MD/PhD support are trotted out with some regularity – trolling through PubMed will turn up scores of them in the last few years. There is in fact already a very large chunk of research funding that is targeted to MD/PhDs. The MSTP program, which you did not benefit from, is the most obvious of these, and it funds the scientific and clinical education of around 1000 students nationally. This is a tremendous investment and one that appears to be made unconditionally – there is not, to my knowledge, any payback requirement for those who opt out of the PhD part of the program, and in the process receive two years of free medical education. It’s a bit difficult to find current numbers on the attrition rate, but an old study (1981) puts it at ~10%.

    At more senior levels, there are both public (e.g., K08 awards) and private (e.g., Burroughs-Wellcome, which has discontinued grants for basic scientists and replaced them with career awards for physician scientists; and Howard Hughes, which has long supported physician scientists, and recently expanded support for this group) funds that are targeted at MD/PhDs. Beyond these targeted mechanisms, NIH grants are in general heavily focused on translational research, which one would expect to benefit MD/PhDs substantially.

    Given these substantial funding commitments, a better question than “How can we increase MD/PhD funding?” is “Are MD/PhDs a good investment?” There’s little question that MD/PhDs are bright people who do well in academia. They are disproportionately represented in academic positions, and in measures of scientific success they do better than their MD colleagues. They publish at higher rates, and are more successful in obtaining NIH grants – roughly on par with PhDs in the latter two categories. But do they contribute disproportionately to translational advances? That is the critical question and remains very much an open question, as it’s precisely these translational advances that MD/PhDs are meant to facilitate. Most studies of MD/PhDs’ impact (mostly MSTP graduates) assess measures of professional success (academic positions, grant success) rather than attempting to quantify translational impact. My MD/PhD faculty colleagues that run research labs operate very much like basic scientists – their primary research interests lie in basic science questions and they publish in basic science journals. They are no more likely to be addressing translational issues than are their PhD colleagues. Nor are they more likely to be involved in biotech start-up efforts*, or to hold more patents – both of which provide very direct measures of the degree to which research efforts are translational. The unexamined assumption that underlies calls for more MD/PhD funding is that this group contributes something unique to the research community. Until this contribution is **quantified** – though stories are welcome, Orac – the wisdom of devoting a larger portion of scarce research funding to MD/PhD careers is questionable.

    *After writing that, I was intrigued, and googled my own small study. Using figures from 2006 for the 10 most successful – biggest revenues – biotech companies, I tracked down the founders for each of these companies. PhDs were vastly overrepresented, accounting for 15 of 18 founders I could track down without much effort; there were no MD/PhDs – the remaining three founders were MBAs! Arguably a better measure would be track down the founders of newer and smaller biotechs, as the number of MSTPs graduated annually was quite small until the mid-1980s or so. If anyone wants to take on this, I’d be interested in the results. Incidentally, given their relative scarcity, chemists seem to be overrepresented among the ranks of the top 10 founders.
    **Some interesting quantification can be found here: http://publications.nigms.nih.gov/reports/mstpstudy/ and also in this (old) Bickel et al study “The role of M.D.-Ph.D. training in increasing the supply of physician-scientists” in NEJM.

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