Respectful Insolence

After diving into a heapin’ helpin’ of sheer craziness over the last week or two (well, except for yesterday, when I deconstructed an acupuncture study, which, while not crazy, certainly was misguided), I think it’s time for a bit of self-absorbed navel gazing. After all, isn’t that what bloggin’s all about? Oh, wait, that’s what I do almost every day here. No, what I really mean is that I came across an article that struck rather close to home regarding my career trajectory. So, if you don’t mind, for one day I’ll leave behind the rabid anti-vaccine loons, the homepaths, the alt-med mavens, and other assorted cranks and look at a problem that I’ve written about before but feel in the mood to discuss again. The impetus for this is an article by Andrew Schafer that was published in Science Careers entitled Perspective: The Successful Physician-Scientist of the 21st Century:

Physician-scientists have always brought a unique perspective to biomedical research that is inspired by their personal experience in caring for patients. Indeed, throughout history, physicians have played a central role in advancing the science of medicine as the “translators” of medical research. Yet there has been growing concern over the past 3 decades that the workforce of physician-scientists, at least in the form we have come to know them in previous generations, may be vanishing.

We have a problem.


When I first read this paragraph, my first thought was that, ever since I entered medical school back in the mid-1980s with the intention of becoming a physician-scientist, I’ve been told “we have a problem,” that there aren’t “enough” physician-scientists. Don’t get me wrong. As much as it may annoy some of the basic science researchers who read this blog, I agree that it is true. Physicians do bring a unique perspective to biomedical research compared to basic scientists. That is not in any way to denigrate the contributions of basic scientists in the least, as (I hope) readers will see. The contributions of physicians and scientists to biomedical research, in an ideal world, should be complementary.

I’ll give you an example that just happened a while back. I was discussing research with a basic scientist, someone whose work is quite good and with whom I was thinking of collaborating. He was quite enamored of a model he had developed of early events in breast cancer cell metastasis. I thought it was a really cool model, too. Unfortunately, I knew it was also clinically mostly irrelevant. Fortunately, I was able to put him on the track of a more clinically relevant model.

Just the other day, something similar happened. I was the only clinician at a meeting of basic researchers, when a point came up about how interesting it was that so many tumors occurred in the upper outer quadrant of the breast. I pointed out that this observation is not really considered striking among surgeons and in fact that the issue has been studied. There happens to be more breast tissue in the upper outer quadrant, and the increased incidence of upper outer quadrant cancers is most likely consistent with that observation.

None of this is meant to be bragging or denigrating the knowledge base of basic scientists. Believe me, as an MD/PhD, I’ve seen it go the other way, where basic scientists (or I) have had to correct an overzealous clinician who thought he had made a new finding and figured out how to investigate it, not knowing that they were treading well trod ground. Collaboration is one way to overcome this. The problem is that, the way academic medicine has been going, there is a perception that there are fewer and fewer physicians who are carrying out translational research who can collaborate with these basic scientists. At least, there are some worrying trends:

There is ample evidence to support this worrisome trend. Although the numbers of National Institutes of Health (NIH) grant applications and applicants over the past 15 years has more than doubled, those numbers have been essentially flat for M.D.-only physician-scientist applicants. During the 5-year period from 1998 to 2003, during which the NIH budget doubled, there was a 43% increase in first-time R01 applicants with Ph.D.s as principal investigators (PIs) and a 104% increase in applications with M.D.-Ph.D. PIs — a very small percentage of the total pool of applicants. In contrast, applications from those with M.D. degrees declined by 4%.

Note that this is referring to physicians with MDs alone who do research of sufficiently high quality to garner NIH R01 funding. Worse, as Dr. Schafer points out, physicians are much less persistent in resubmitting grants after the inevitable rejection of the first application. Anecdotally, my experience bears this relative decrease in MDs doing research, particularly in surgery. Back when I was a medical student and resident, not only did I meet and get to know several surgeons without PhDs who had their own labs and did research, I worked with a couple of them. These days, I know only a couple, only one of whom can be described as continuing to be successful at it while still maintaining a clinical practice. All the other MD-researchers who have remained successful that I know have given up clinical practice. Meanwhile, at academic surgery conferences that I attend, a constant theme is the lament about how difficult it is to get a career in research, how few surgeons–and physicians in general–want to do research anymore.

Of course, as I’ve alluded to in the past, the forces arrayed against even the most dedicated physician wanting to do research are considerable. Reimbursements from third party payors and government sources continue to be ratcheted down. As a result, the pressure to do more and more clinical work just to carry one’s own weight continues to be a serious problem. As much as medical schools would seem to like to believe that clinicians will spend their nights and weekends doing nothing but extra work, such an expectation is not realistic.

One observation that Dr. Schafer makes that is particularly accurate to me is this is when he speculates as to how it might have happened that there are decreasing numbers of physician-scientists and that at every step in the early life cycle of NIH grant funding they tend to disappear from the pool:

At the core of it, I think, is the reality that the arenas of basic biomedical research (on one side) and the clinical practice of medicine (on the other) have progressively and dramatically separated. This widening chasm has created a rapidly increasing language barrier between basic biomedical scientists and practicing clinicians. It is a two-way barrier: Midcareer clinicians today are unable to understand even the basic vocabulary of molecular biology and genetics, and biomedical investigators (even those with M.D. degrees) are increasingly losing track of rapid advances in clinical medicine, which is always increasing in technologic complexity.

And it’s true. Physicians who don’t stay continually active doing research and interacting with basic scientists very rapidly fall behind, to the point where they no longer even understand the basic science. I must admit, however, that I hadn’t considered so much that this increasing distance might be due to movement on both sides, but now that I think about it it does seem to ring true. Most basic scientists aren’t aware of advances in how we clinicians treat, for example, cancer.

I’m not sure I entirely agree with Dr. Schafer, though, when he also blames this increasing chasm on the “he reductionism in medical research in the early years of the molecular biology and genetics revolution throughout much of the second half of the 20th century.” I do see his point, though. It is true that, at least during most of my medical career, science did move in an increasingly molecular direction. It’s also true that, from my perspective, in the 1980s to 1990s it seemed that very few basic scientists did anything resembling whole organ or whole organism physiological studies, preferring instead molecular biological approaches. This tended to leave studies of whole organ physiology mainly to physician-scientists. To put it simplisticially, basic scientists dealt with genes and proteins; physicians would look at macroscopic phenomena, like blood flow and grose measures of metabolism. What I don’t see happening is Dr. Schafer’s prediction that systems biology will help bridge the chasm between clinicians and basic scientists.

It may well be that systems biology may serve to nearrow this gap, but I wouldn’t count on it. The reason, of course, is that systems biology requires ever more advanced molecular and mathematical models in order to construct the signaling networks based on experimental data. If anything, it’s molecular biology on steroids, requiring specialized mathematical and statistical calculations, not to mention a whole lot of computing power.

One characterization of this chasm that I do (mostly) agree with comes from Barry Coller:

  • Clinicians are motivated by the need for immediate action (sometimes to even save a life), whereas scientists are conditioned to avoid rushing to judgment;
  • Clinicians are taught to adhere to standards and guidelines of practice, whereas scientists are encouraged to challenge existing paradigms;
  • Clinicians traditionally respect hierarchy and expert authority, whereas scientists tend to critique and challenge accepted wisdom;
  • For clinicians, errors are potentially mortal threats, whereas for scientists, errors are inevitable manifestations of the creative process;
  • Clinicians focus on the unique, whereas scientists look for generalizable principles.

The only part of this I tend to disagree with is the last principle. Clinicians don’t just focus on the unique; they are taught from the very beginning of medical school to look for patterns. The real difference is that this pattern recognition isn’t always systematic. Often it works on the level of an overal “gestalt.” If there’s one thing a good clinician can do, it’s to tell when a patient “looks sick.” The best clinicians can walk into a room and at a glance have a good idea of just how seriously ill a patient is, and the very best surgeons can often identify peritonitis before they even lay a hand on the patient. Of course, this is just as much a cultural difference between physicians and basic scientists, the latter of whom rely on experimentation, hypothesis testing, and observation to come to their conclusions. It’s also sometimes a serious problem in that physicians without training in the scientific method all too often let their pattern recognition skills lead them astray into confusing correlation with causation and confusing placebo effects and regression to the mean for real responses to therapy. I can’t help but speculate that this is one reason why physicians tend to be more prone to woo than they should be.

So what does this all mean?

A lot of this strikes me as a case of “everything old is new again.” As I mentioned at the beginning, I’ve been hearing about the imminent demise of the physician-scientists, well, ever since I started training to become one. Sometimes I have to wonder whether some of this rhetoric is, either consciously or unconsciously, designed to reinforce a sense of importance in the endeavor. On the other hand, it is important to be able to translate basic science findings into clinical practice. What we may well be observing is not so much the demise of the physician-scientist, but its evolution. There used to be a time when a person with an MD could pick up research skills by spending a couple of years in a laboratory under the tutelage of a research mentor and end up with the research skills necessary to be competitive for NIH funding. That time is no more. Consequently, what we are seeing now is the rise of the MD-PhD as the preferred physician-scientist, leaving the MDs to take care of the patients. The problem is that there aren’t a lot of MD-PhDs, and there likely never will be. Few people are dedicated or crazy enough to get both degrees, go through a demanding residency, and then try to compete with basic scientists for grant funding. Sometimes I don’t know if I’m crazy enough to do it anymore.

Perhaps the most relevant observation made by Dr. Schafer is this one:

Learn that medical research today is a team sport. During this generation, the breathtaking pace and scope of progress in both the science and the practice of medicine has vastly outstripped the capacity of any individual physician-scientist to maintain even a semblance of currency in both arenas. The key to success is your ability to thoughtfully surround yourself with partners, particularly Ph.D. scientists, who offer complementary expertise. And for each project, you and your collaborators should try to agree in advance what each scientist’s role will be and who will be the “driver.” Insisting on being the sole principal investigator on every project, or even most projects, will prove to be counterproductive. Can you be a team player and still be a star? Yes. Remember that the greatest sports stars have been the ones who were able to elevate their teams to win championships.

And that, above all, is the major change that has occurred over the last 20 years. Solo investigators running their own little labs are going to have an increasingly difficult time suriving, and that goes for both basic scientists and clinicians. Both are needed to maintain the pace of progress of science-based medicine. If one, the physician-scientist, is endangered, it’s going to be very hard to figure out how to apply all that fancy science, either reductionistic or systems biology, to improve the care of actual patients.

Comments

  1. #1 JohnV
    June 2, 2010

    I’ll just take this time to note my admiration for you guys. I can barely keep up with being a basic scientist, it seems like every couple of days I have something completely new (to me) to learn about. I cannot imagine coupling that with being a physician.

    And if I might be so bold as to make a programming request, perhaps you could briefly discuss the difference between the degrees and how they’re relevant to science? One of commentors who shall not be named (for fear of entering the moderation queue) demonstrated a profound ignorance of the topic yesterday :p

  2. #2 Steve
    June 2, 2010

    I’m a senior in undergrad right now, in the middle of applying for MD-PhD programs… and not a day goes by that I don’t wonder whether I’m completely insane. I want to do research, but I also want to see patients–It shouldn’t be as hard as it is to do both. I really seriously wonder whether it’s wise for me to give up the years of my life for the extra degree. Will I be able to keep up with my fellow doctors while doing research? Will I be able to compete for grants with basic science researchers while taking care of patients? How will I have enough time to do both? I enjoy both and can’t see giving either one up… Oh well, I’ve always been a little insane in the plasma membrane, I guess. I sure hope the physician-scientist isn’t endangered: I don’t want to be the only one left after my 14+ years of training are over.

  3. #3 Cassidy
    June 2, 2010

    It seems that some organizations, or at least HHMI, are addressing this problem from another angle with the molecular medicine certification program. My school is starting it for next year (I’m applying, fingers crossed and all), and it’s a three-year endeavor to give basic scientists clinical experience. Basically you get a clinical mentor, have to shadow her or him for a certain number of clinical hours, fill hours of relevant didactic lectures/seminars and attend clinical conferences. Although it obviously isn’t going to make any of us clinicians (I mean, I didn’t WANT to be an MD, that’s why I WENT to grad school and not med school), I hope that it will serve to teach those of us removed from the bedside (I’m in an evolution department) to communicate effectively with clinicians and improve our ability to think translationally.

  4. #4 Elaine Schattner, M.D.
    June 2, 2010

    Orac,
    Thanks for another super-thoughtful post.

    I really hope that this and the next generation of academic medical leaders can provide a better way for thoughtful physicians with innovative ideas to thrive, or at least survive, in the super-competitive medical research environment.

  5. #5 hank
    June 2, 2010

    whaT would happen if a whole lot of spece began to disapper?

  6. #6 MitoScientist
    June 2, 2010

    I think its worth noting that a barrier to creating physician-scientists also lies in admission to the specialized programs for them. Few people have the patience (and money, I suppose) to earn one degree, then turn around and apply/earn the second. As such, the combined degree programs are where most duel degree folks come from, and those can be insanely competitive to get into. If there is a serious worry about a shortage of MD/PhDs, then something should be done to facilitate more people in the combined degree programs. And I say this as a PhD student seriously thinking about med school after, even though it’s a completely backwards way of going about things.

  7. #7 Serdar
    June 2, 2010

    An excellent post, Orac.

    Based on what I’ve seen from having read this column for a while now, I’ve noticed that the anti-everything loons never have comments on posts of this ilk. The reason for that should be obvious: they have no interest in science and medicine as it is actually practiced.

  8. #8 Rene Najera
    June 2, 2010

    So my “other” job is that of a Medical Technologist at a hospital. I basically run the lab on overnights, blood bank, microbiology, chemistry, hematology, etc. I get to experience some very painful moments of “are you f-ing kidding me?” with some physicians.
    For example, one physician asked me to do a Gram stain on a stool sample. Another physician asked me why we did penicillin sensitivities on organisms when no one uses penicillin anymore. And yet another told me to my face that she knew of no other professional in the hospital who was more exposed to pathogens as physicians were. True stories, all of them.
    I know physicians go through a lot of schooling, and, for the most part, they’re all very bright people. But I am astounded at the lack of knowledge in some areas though they act like they know what they’re talking about.
    FYI: Hyperkalemia in a patient with a 900 platelet count should be repeated on a plasma sample… just for kicks… and preferably before you treat an asymptomatic patient for it.

  9. #9 JohnV
    June 2, 2010

    “Here’s the Gram stain results on the stool sample. Yes.”

  10. #10 antipodean
    June 2, 2010

    I work with loads of MD PhDs and we are constantly training more of them.

    Any decline in the numbers of people doing this is because the PhD side is underpaid and risky as hell. MD work is safer and better paid.

    -antipodean

  11. #11 rork
    June 2, 2010

    We sure do need those physicians to be part of the team, and not just in “translational” research, and not just physicians. A problem for me is that the best physicians, that I want (nay, need) to quit seeing patients, and work in the research trenches full time, have a hard time doing that. Perhaps their departments make it hard for them to make the transition gradually. The ones I know mostly have PhD too, but for a beautiful mind who cares about degrees (thinks of J. Quackenbush, not the only cool biologist educated as a physicist). If they write pretentious doctorese (where “define” means to observe or measure), then I have a problem. Engineers, computer wonks, math nerds (I’m one), we need you too. Biology is cool.

    MitoScientist: I once had the pleasure to daily confer with a beautiful man, James V. Neel, PhD zoologist first, MD second, after realizing he’d be needing that too, to really do what we call human genetics now. You go.

  12. #12 Mac
    June 2, 2010

    Re #8: “For example, one physician asked me to do a Gram stain on a stool sample.”

    Why was the doctor asking for this? Is that always a dumb request?

    (I ask after reading, http://www.nlm.nih.gov/medlineplus/ency/article/003757.htm)

  13. #13 Schwa
    June 2, 2010

    Gram stains turn gram positive bacteria purple. Stool is
    mostly bacteria, so if you gram stain it, you’ll get a mostly useless purple smear.

    Orac, I’ve been wondering about the viability of another approach: my fiancée works in a lab where the MD PI write grants and gets samples, and the PhD lab manager carries out most of the experiments. I am a med 1; do you think it would be worth trying to set up a similar lab once she has her PhD and I’ve finished residency?

  14. #14 marie
    June 2, 2010

    As a (very near) future med student interested in molecular biology, I find this issue to be very relevant. I wholeheartedly agree that learning how to collaborate with other physicians and scientists, not only in medicine, but in other fields as well (like rork @11 mentioned), will be important for anyone doing research in the medical field.

    I don’t know too much about the details, but something like the Bio-X program at Stanford seems like a step in the right direction.

    Thanks for the post! It’s my first time commenting but I’ve been an avid reader for several months now =)

  15. #15 Mac
    June 2, 2010

    Re Schwa #13: It isn’t “all purple,” actually. Gram negatives (such as your enteric rods) gram stain pink. Yes, about 50% of the mass of stool is bacteria. But, I ask again: does that always render a fecal gram stain useless? And if so, why does Medline have a web page on this test?

  16. #16 Mac
    June 2, 2010

    …And if you want to talk about “useless” tests… what about ESR?

  17. #17 Dianne
    June 2, 2010

    There are in fact a few situations in which the ESR is useful, but mostly getting an abnormal ESR on a sick person just proves that the lab was open that day.

  18. #18 gwen
    June 2, 2010

    My hospital is trying to make nursing research a part of the criteria to maintain our staff nurse levels. We would have to continue to do our bedside nursing commitment and find our own grants to do the research on our own time. We are NOT happy about this, I am told that it is becoming part of our industry standard although I have not researched it. The hospital seems more interested in nursing research than quality nursing care.

  19. #19 Roger Rains
    June 3, 2010

    “There are in fact a few situations in which the ESR is useful, but mostly getting an abnormal ESR on a sick person just proves that the lab was open that day.”

    Ahh… but a normal ESR lets you mostly quit worrying about a whole host of nasty problems. Lab tests aren’t only useful when they are positive.

    -RR-

  20. #20 ltbear
    June 3, 2010

    I’m a high school grad going to college this year. I’ve been interested in the MD/PhD training for some time, since I want to be a physician-scientist who does translational research.

    Thing is, I’m not that interested in taking care of patients. Should I plan to take PhD only instead? But I’m interested in doing translational research/clinical trials to develop treatments, instead of doing basic research. Can a PhD-only graduate do this? Is it worth spending 4 years medical school if I don’t have a passion in treating patients?

  21. #21 Chris
    June 3, 2010

    ltbear, you should concentrate on getting through your first year of college.

    Even though you may have entered as a junior due to AP credits or classes taken in a community college as a high school student, it is a big change.

    I am the parent of a freshman college student. He walked in with at least a full quarter of credits, and while he is doing okay, several of his friends are not. So just concentrate on getting in your basics, and take advantage of your university’s advisers.

    You might want to read Gina Kolata’s book, Flu!, where she details the career of an MD/PhD (and his name escapes me right now!).

  22. #22 Rene Najera
    June 3, 2010

    The ESR is being replaced by the CRP lately, which is just as useless (but faster to perform).

    And God only knows why there would be a Gram stain on stool procedure.

  23. #23 Dianne
    June 3, 2010

    Ahh… but a normal ESR lets you mostly quit worrying about a whole host of nasty problems.

    True, but that’s why I said “on a sick person”. I should add that “sick” in this context is shorthand for “sick enough to be hospitalized”. Generally, that leaves out the population on which an ESR is most useful. For example, determining the difference between osteoarthritis versus something autoimmune. Or considering irritable bowel versus some inflammatory bowel conditions. But an ESR on someone hospitalized for, for example, pneumonia or sepsis is kind of a dadaist test. If it were negative that would simply mean that it was done wrong. Yes, people occasionally do order tests this silly.

  24. #24 Dianne
    June 3, 2010

    Back to the original topic…People have been moaning about the lack of physician scientists since at least the 1990s when I was in med school. But no one seems to want to enact the obvious solution: make it easier for physicians to be scientists. Make protected time truly protected, make funding easier to obtain for clinically relevant projects, make sure hospitals consider time spent in research as service to the university and don’t penalize physicians for not seeing patients during that time, etc. Until that happens of course there will not be many physician scientists. If you make it impossible to do something, people won’t do it. End of story.

  25. #25 Mac
    June 3, 2010

    Re #22:

    Here’s a brief excerpt from the UpToDate article on Cholera:
    “Gram’s stain of stools may show sheets of curved gram-negative rods, as untreated patients can have 10(6) to 10(8) organisms per mL of stool [42].” Cholera outbreaks were reported in Louisiana after Hurricane Katrina, incidentally.

    I still ask my original question in earnest, although the Vibrio example just took me a few minutes to find. I don’t know what specific clinical protocols would call for a fecal gram stain these days. Maybe a culture or another microscopic imaging technique would be more appropriate in this case.

    But– to use a gram stain as an unqualified example of when you ask a doctor “are you f-ing kidding me,” is, I believe, un-called for. I can think of too many plausible scenarios (i.e. one or more) in which a reasonable doc orders this test. I don’t know what kind of technology your lab boasts, but so far all you’ve been able to say is that you don’t know why the doctor ordered it. You have not explained why it’s always a really dumb idea.

    Even if it is not strictly the best diagnostic option, it could be a pretty cheap, fast, easy way to confirm a diagnosis in certain situations. And in some cases, the clinician might be working with limited laboratory tests. But you can do a gram stain almost anywhere in the world.

    I’m not saying you’re wrong. I’m just asking if you picked the best example in this case, and whether you’re right or wrong, we’ll all learn something, right? :)

    It’s gotten a little off-topic from Orac’s story, but maybe there’s an ID person out there who could chime in.

  26. #26 Tybo
    June 3, 2010

    As (another) senior in undergraduate studies, I also wonder about the addition of a PhD onto an MD program. Mostly, I fear that I would lose touch with modern research without the former, even if my primary intent is to work in a clinical setting. How reasonable is it to do research as just an MD? I recognize that this is possible during summers in many med schools, but I don’t see any evidence that it really continues beyond that.

    … Further, MD/PhD programs are competitive enough that my chances are rather slim anyway. My record, while rather good, isn’t stellar enough to scream “pay me to go through medical school and PhD training!”

  27. #27 Mac
    June 3, 2010

    Tybo- your resume on paper isn’t everything. Interviews and real-world experience have a huge impact and can really overcome some big deficiencies in your academic record. Also, many med schools offer the flexibility to join a dual degree program (including MD-PhD) after you matriculate as a MD student. Not only that, but your acceptance chances can be hugely improved via that route. In the grad school world, paths are often a lot more meandering or flexible than you might assume.

    I didn’t apply for a dual program directly. I entered med school and planned to apply for the PhD program later. I did indeed open up that door, but decided at that particular time that it wasn’t what I wanted to focus on.

    The very best thing you can do: just do what you find interesting, and don’t worry about the money, or the resumes, or checking boxes. And you’ll probably create a very fulfilling career for yourself, no matter which route you go.

  28. #28 Kel
    June 4, 2010

    I am in awe of anyone who can manage to complete an MD/PhD. I didn’t decide to go to college until I was 27 and 8 months pregnant, but now I have been working in a clinical lab for 3 years, recently transferred to Micro because it seems like my true calling, and have one more year to become a medical technologist.

    I guess my point is, that even as a lowly lab assistant I can recognize that a lot of the orders we receive don’t make much sense. FTR I have never been asked to do a gram stain on stool, and I just double checked our test manual and there is no mention of it. Nurses do seem to have a really hard time ordering urine cultures correctly though, they will order UA/CIF then call back 3 days later asking why there is no culture and we tell them it wasn’t indicated, the sample has exceeded stability, please recollect, and then they send the same thing in again! 3 times to get it ordered correctly.

  29. #29 Tybo
    June 4, 2010

    Mac – Thank you for point that out. I suppose many colleges don’t go out of their ways to advertise that it’s possible to join the dual degree program after the fact? In any case, I feel a lot more comfortable recognizing that the possibility exists.

  30. #30 Xplodyncow
    June 5, 2010

    (I hope this question is at least somewhat relevant.)

    So who attends conferences (etc.) like ASCO?

  31. #31 jpoker27
    June 7, 2010

    I’m currently a medical student who wants to do research in genomics/proteomics. Am I going to find it difficult to find a medical center/university who wants only an MD with no research experience??

  32. #32 MD
    August 15, 2010

    Physician scientists face ever increasing hurdles with regard to clinical demands, financial demands, regulatory compliance and teaching responsibilities. This is on top of the increasing difficulties and time requirements involved with obtaining research funding. Add to this the fact that most physician scientists finish their residencies at an age when many are starting families which leads to shifting priorities and increasing financial requirements (on top of any debts they may have accrued already). Many (even the MD-PHDs), at this point, realize that life will be much easier (and still fairly rewarding) if they utilize their very marketable and financially rewarding clinical skills rather than scientific skills.

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