"Translational" Research

[tedrik]

I am just looking for a definition of "translational" when talking about translational research. Is this a broad term that suggests there are clinical applications for the basic science being done, or does this imply that there is actually clinical work being done?

Specifically: If I say that I am interested in translational research, am I telling them that I actually want to be the one applying research discoveries to human patients, or that I would like to run a lab that does medically driven basic science?

Maybe the actual definition is a bit blurred and dependent on context, but any input would be appreciated.

Thanks!

---

Members don't see this ad.

 

[b&ierstiefel]

Translational research is a very broad concept but in general describes research that attempts to draw closer together the "bench and the bedside." Clearly this can signify many things such as elucidation of molecular targets for various drug design, performing clinical trials, etc. My impression is that doing translational research in the purest sense (the perfect mix of basic science and clinical research) is very difficult. Part of this is because many people think that it is good to focus in on one area and be productive in that area. Hence many researchers do work that is more basic science oriented or predominantly clinically oriented.

I never had to go much into this during interviews. You can say that you would like to do translational research in the future...the mudphuds love that. On MSTP interviews, however, you'll be asked to describe in detail and demonstrate your understanding of your undergrad projects whether basic sciency, clinical, or both. It is very difficult to know what you will want to do 10 years from now after you complete MD/PhD training and do stuff afterwards. Much of that depends on being at the right place at the right time and seizing any opportunity that presents itself.

 

[BDavis]

Although I am getting close to finishing my MSTP, for me it is still a little unclear what translational research is. However is a definition from my school that might shed some light.

"Clinical investigation is here defined as hypothesis-driven, patient-oriented research on human subjects (or on material of human origin, such as tissues), in conjunction with laboratory measurements as appropriate, in clinical biology, natural history, prevention, screening, diagnosis, therapeutic interventions, clinical trials, epidemiology of disease, behavior, mechanism of disease, and the efficacy and effectiveness of health care delivery (outcomes research and health services research). Included in this definition is "translational" research, which bridges the application of information between the laboratory and new methods of diagnosis, treatment, and prevention and is thus essential to our progress against diseases. Excluded from the definition are in vitro studies that utilize human tissue but do not deal directly with patients."

 

[b&ierstiefel]

Although I am getting close to finishing my MSTP, for me it is still a little unclear what translational research is. However is a definition from my school that might shed some light.

"Clinical investigation is here defined as hypothesis-driven, patient-oriented research on human subjects (or on material of human origin, such as tissues), in conjunction with laboratory measurements as appropriate, in clinical biology, natural history, prevention, screening, diagnosis, therapeutic interventions, clinical trials, epidemiology of disease, behavior, mechanism of disease, and the efficacy and effectiveness of health care delivery (outcomes research and health services research). Included in this definition is "translational" research, which bridges the application of information between the laboratory and new methods of diagnosis, treatment, and prevention and is thus essential to our progress against diseases. Excluded from the definition are in vitro studies that utilize human tissue but do not deal directly with patients."

congrats for being almost done with MSTP training. it's quite a long haul ey?

 

[tedrik]

Forget what I said about the deffinition being "blurred." Thanks for clearing it up for me BDavis and AndyMilonakis.

Congrats to both of you on nearly being done!

 

[BDavis]

congrats for being almost done with MSTP training. it's quite a long haul ey?

Almost too long, if I had graduated one year earlier I could of taken Step II without the clinical skill exam. I take it you are almost done too (we can look forward to getting our AARP memberships and the special discount at IHOP). When I return I have to take Step II with the new clinical skills exam as well as a "practice clinical skills exam" that costs an additional $1000. The good thing is when I return my classmates will be my upper levels and attendings.

 

[b&ierstiefel]

Almost too long, if I had graduated one year earlier I could of taken Step II without the clinical skill exam. I take it you are almost done too (we can look forward to getting our AARP memberships and the special discount at IHOP). When I return I have to take Step II with the new clinical skills exam as well as a "practice clinical skills exam" that costs an additional $1000. The good thing is when I return my classmates will be my upper levels and attendings.

Yeah BDavis, I'm almost done as well. Actually I'll be done with all of my requirements in less than 2 months. Afterwards, 8 months of random stuff...ahh the light at the end of the tunnel becomes brighter as the days go by

I had the option of defending my PhD one year earlier. But I figured that I would take an extra year to wrap up a few projects at a leisurely pace. Plus, I wasn't mentally ready to go back to med school...but in retrospect, I wasn't ready to become an M3 student last year either.

In retrospect, I should've finished my PhD one year early. Main reason being that I wouldn't have to take that damned Step 2 CS (total money scheme if you ask me). Plus, in terms of classmates, I would prefer to have the class of 2004 people as classmates rather than the class of 2005 people. The class of 2004 was considered as the "nice class"; I had the pleasure of being their biochem TA when they were M1's, and they were genuinely very nice bunch of folks. Apparently, the class of 2005 at my school is known as a bunch of whiners and some of the faculty I've run into have openly stated that they don't like our class.
Oh well, hindsight is 20/20. What are you going into now that you're almost done and starting this whole residency application process?

 

[BDavis]

Yeah BDavis, I'm almost done as well. Actually I'll be done with all of my requirements in less than 2 months. Afterwards, 8 months of random stuff...ahh the light at the end of the tunnel becomes brighter as the days go by


I envy you, I still have about 9-11 months of clinical rotations left. I am surprised my white coat still even fits (or is even white; it makes a great rag in a pinch if you spill Kool-Aid).

>In retrospect, I should've finished my PhD one year early.
This idea seems to be reiterated among many of the upper class MSTP students; although some have stayed around to do a 1 year post-doc in the same lab as their thesis to sync up with medical school.

>Apparently, the class of 2005 at my school is known as a bunch of whiners and some of the faculty I've run into have openly stated that they don't like our class.
Hopefully your evaluations won't suffer as a result of the "reputation of the class". Although we have a line item veto for our Dean's letters I don't want to really use it unless I really need to. So far I have been lucky and no one has trashed me in the evaluations.

What are you going into now that you're almost done and starting this whole residency application process?

> I enjoyed my internal medicine clerkship so I will probably do a couple sub-internships at California schools (I would like to train elsewhere besides TX) just to make sure it is what I want to do. I am very fragile when it comes to cold so I need to find a place without snow(I lived in New York City for a while and that was way too cold for me). Dermatology looks interesting, but I need to do an elective to see how I really like it. I have also thought about Pathology and Rad Onc, but I have not done the rotations. How about you? Ready for some place warmer yet?

 

[b&ierstiefel]

> I enjoyed my internal medicine clerkship so I will probably do a couple sub-internships at California schools (I would like to train elsewhere besides TX) just to make sure it is what I want to do. I am very fragile when it comes to cold so I need to find a place without snow(I lived in New York City for a while and that was way too cold for me). Dermatology looks interesting, but I need to do an elective to see how I really like it. I have also thought about Pathology and Rad Onc, but I have not done the rotations. How about you? Ready for some place warmer yet?

Yeah, I'm up at Michigan. I've gotten used to cold weather but it's still not pleasant during the cold heart of winter. As for the field, I'm applying to pathology programs. Initially (a long time ago, before doing the medicine rotation), I was thinking of IM because I was told that people who do research go into IM. Pathology is also research heavy and when I didn't enjoy myself on the IM rotation, I thought of pathology. I'm currently doing a path elective during this month and next month...and lemme tell ya, I'm totally loving it.

 

[BDavis]

Yeah, I'm up at Michigan. I've gotten used to cold weather but it's still not pleasant during the cold heart of winter. As for the field, I'm applying to pathology programs. Initially (a long time ago, before doing the medicine rotation), I was thinking of IM because I was told that people who do research go into IM. Pathology is also research heavy and when I didn't enjoy myself on the IM rotation, I thought of pathology. I'm currently doing a path elective during this month and next month...and lemme tell ya, I'm totally loving it.

One of our MSTP students matched at Hopkins for Pathology and she seemed to really like the program because it truly protected your time for research. I think she looked at the Boston programs, Wash U, Duke, U Penn and U Wash. I forgot if she did AP or CP, but she also wanted protected time to do research. From what I have heard, IM program claim to give you protected time to do research, but they don't really cut you any slack in terms of reducing your clinical responsibilities. For me I haven't quite figured out if I could stand writing grants all the time (I am writing a paper and my thesis nw and it is really boring); I have talked to researchers at the NIH where you don't really have to write formal large grants and they seem to really enjoy it so maybe I'll take a look into that.

 

[b&ierstiefel]

One of our MSTP students matched at Hopkins for Pathology and she seemed to really like the program because it truly protected your time for research. I think she looked at the Boston programs, Wash U, Duke, U Penn and U Wash. I forgot if she did AP or CP, but she also wanted protected time to do research. From what I have heard, IM program claim to give you protected time to do research, but they don't really cut you any slack in terms of reducing your clinical responsibilities. For me I haven't quite figured out if I could stand writing grants all the time (I am writing a paper and my thesis nw and it is really boring); I have talked to researchers at the NIH where you don't really have to write formal large grants and they seem to really enjoy it so maybe I'll take a look into that.

Yeah, I applied to all those programs...20 in all...probably too much considering it's pathology. Oh well, at this stage of the game, I guess it can't hurt to apply to many.

I agree with you on IM. There are short track residency programs in IM where you have only 2 years of clinical responsibility instead of 3. Thing is...your 2 years is jam packed with strenuous work which is usually distributed normally during 3 years. So residency becomes more hellish...unless IM agrees with your personality and work preferences.

Writing grants can get pretty boring...not that I've written any . However, grants, like clinical duties, can be a source of stress. It's a different kind of stress but stress nonetheless. In general, every field or discipline has its good and bad sides...there is work that one can enjoy doing, then there's work that is unpleasant to do but is just part of the job. Clinical scut vs. basic science scut...I figure I'm more tolerant to the latter. However, everyone's different.

P.S. Scut sucks but it all depends on what you call scut. For instance, on our IM rotation here, scut is defined as having to do stuff for patients we are NOT involved in taking care of. However, no matter how crappy the work is, if the work pertains to your patient, it's not scut. Given that, let's extend that to research. Experiments, grants, etc apply to your project...so I guess it technically ain't scut.

 

[BDavis]

Yeah, I applied to all those programs...20 in all...probably too much considering it's pathology. Oh well, at this stage of the game, I guess it can't hurt to apply to many.

Writing grants can get pretty boring...not that I've written any . However, grants, like clinical duties, can be a source of stress.

Even writing grants can be boring for me, I am more concerned about getting it after spending all that time to write one. I have been lucky to get the grants I write for, but they are training grants (the payline can be as high as 50%). A full fledged R01 is a different story and many people remind me not to feel bad if I don't get my first, second or third R01. Given that the paylines for these grants are sometimes as high as the ~10-12% percentile, it is a little unsettling, but it doesn't completely discourage me from pursuing research (it sort of like those attendings who always tell you that you should never do medicine in the first place).

 

[zep]

Check out this article:
Science, Vol 300, Issue 5626, 1680-1685 , 13 June 2003
It is part of Floyd Bloom?s Presidential Address to AAAS a couple years back. He brings up some points that should really make us question what translational research is, or at least what it is intended to be.

 

[Primate]

Translational research. The idea of it, bringing the bench to the bedside and pushing the limits of medicine in new and productive directions, was really what seduced me into the MSTP.

Hindsight being what it is, I was a bit naive to think that one person can really be at both ends of the process while in academia. Perhaps others will disagree, and there are surely a few exceptions, but the majority of MD/PhDs are either at the bench or the bedside, and narry the twain do meet. The pressures and requirements for success in academia (defined narrowly here as a large research university /c affiliated hospitals) are such that one really needs to publish basic science work or see enough patients to generate income justifying one's salary. In either case, you need to sing for your supper.

I'm not entirely sure why, perhaps there is a minimum scale impossible to meet with even the largest university labs, but bio/pharma/device companies seem to be where most translational work is done, at least in the sense of developing and bringing new medical therapies and surgical devices TO PATIENTS.

To be sure, none of that would be possible without the huge and vitally important work done in universities and the like. However, the real bench to bedside appears to occur outside this track.

Any thoughts? I'm sure many will disagree. If you do, I'd like to know why, as this is a particularly important issue to me.

Off to bed now - gotta check off little boxes on the wards tomorrow (stop by the path forum for that reference).

Best,
P

 

[linuxizer]

To be sure, none of that would be possible without the huge and vitally important work done in universities and the like. However, the real bench to bedside appears to occur outside this track.

I was thinking about this today, as it turns out. I came to the conclusion that most researchers I know either do bench-to-bedside or bedside-to-bench. This sort of defies the MudPhud ideal of "bench-to-bedside and back again." The bedside-to-bench seems to be the perview of academia; bench-to-bedside, big pharma. And, oddly enough, in many cases bedside-to-bench doesn't require an MD at all. Rather, I know many PIs who are working on basic science with an applied bent who understand a particular disease in their field at least as well as many MD's--not to say I'd want them treating me, but their knowledge of the disease is sufficient at a molecular and pharmacologic level to ensure they can apply relevant clinical phenomena to their project. This will become an increasing trend, I'd imagine, since the NIH seems to be moving away from basic science with no immediate clinical application.

--Ari

 

[tedrik]

Hindsight being what it is, I was a bit naive to think that one person can really be at both ends of the process while in academia.

I have heard of people being able to fulfill both roles, but is it a bad thing if they don't? I am currently applying to MSTPs with the career goal of conducting basic research. I would like to be able to incorporate patients in my future profession, but above all I want to run an academic lab. Is an MSTP considered unsuccessful if the majority of its graduates end up doing either all clinical or all basic work?

 

[b&ierstiefel]

Is an MSTP considered unsuccessful if the majority of its graduates end up doing either all clinical or all basic work?

Not at all tedrik. On the other hand, the NIH does NOT like it when MSTP students get the first 2 years of med school education free and then drop out of the program (without doing any grad school) and finish the last 2 years of med school.

 

[mjs]

You're right, the word has a touch of fungibility to it. Just be explicit about what you mean when you're talking or writing.

For an interesting look (that is hundreds of pages long) on the subject of what research is translational, what's basic and what it all means, check out science and the quiet art by david weatherall.

I am just looking for a definition of "translational" when talking about translational research. Is this a broad term that suggests there are clinical applications for the basic science being done, or does this imply that there is actually clinical work being done?

Specifically: If I say that I am interested in translational research, am I telling them that I actually want to be the one applying research discoveries to human patients, or that I would like to run a lab that does medically driven basic science?

Maybe the actual definition is a bit blurred and dependent on context, but any input would be appreciated.

Thanks!

 

[Primate]

FYI, MSTPs consider someone going into strictly basic research a success, but someone going into "just" clinical medicine (no research - even a teaching academic is a failure as they don't get grant $$) to be a failure of the program.

There is absolutely nothing wrong with doing all of one or the other, but the MD/PhD is all about doing both - at least in theory. Otherwise, one would only get one degree or the other.

P

 

[b&ierstiefel]

FYI, MSTPs consider someone going into strictly basic research a success, but someone going into "just" clinical medicine (no research - even a teaching academic is a failure as they don't get grant $$) to be a failure of the program.

Hey Primate, I think I can echo this point you make. The attitude is similar here...however, the program here may be tongue in cheek about thinking negatively about those who go into "just" clinical medicine. Our program is usually very proud of anyone who finishes the program. I went into the MSTP office this afternoon during a break in the action to sign the NIH termination form (since I'm practically done). The people in the office all said, "we're so proud of you." That was a big bright spot in the day because I haven't really had the chance to take a step back and realize what kind of an achievement it is to finish an MD/PhD course of training.

 

[BDavis]

The people in the office all said, "we're so proud of you." That was a big bright spot in the day because I haven't really had the chance to take a step back and realize what kind of an achievement it is to finish an MD/PhD course of training.

Personally for my MSTP class, half of us dropped out so the best we can do is a 50% graduation (assuming no more of us drop out during our final years in graduate school). Graduation from a MSTP is certainly something to be proud of. Regardless of the final career choice, our program (Baylor) doesn't seem to mind; we have invited back former MSTP students who work in industry or pure private practice to come and talk to us about career choices (i.e. they don't seem to "hide" those that didn't do research or stayed in academics).

 

[b&ierstiefel]

Personally for my MSTP class, half of us dropped out so the best we can do is a 50% graduation (assuming no more of us drop out during our final years in graduate school). Graduation from a MSTP is certainly something to be proud of. Regardless of the final career choice, our program (Baylor) doesn't seem to mind; we have invited back former MSTP students who work in industry or pure private practice to come and talk to us about career choices (i.e. they don't seem to "hide" those that didn't do research or stayed in academics).

Ah...you go to Baylor. Nice. I remember meeting a bunch of you all at the National MD/PhD conference a few years back in Aspen. There were 6 of us from Michigan's MSTP but there were like 8-10 of you all...I think you guys had the biggest contingent from any given MSTP program.

Random point: Interestingly, I met one of your recent graduates at the meeting. Go figure, he was working in the same field I was working in. I'm talking EXACT same field as one of the mammalian proteins I discovered was orthologous to one of the Drosophila proteins he was working on! Quite unexpected considering that many of the people there were involved in a diverse array of projects. Anyways, I remember talking to him at length regarding our projects and one little piece of information he told me really helped in terms of getting my research project in the right direction.

Anyways, he's considered one of the superstars at your program...dunno where he ended up but I'm sure he's doing quite well regardless of what he's doing.

 

[BDavis]

Anyways, he's considered one of the superstars at your program...dunno where he ended up but I'm sure he's doing quite well regardless of what he's doing.

If your Ph.D. was on crumbs in epithelia then that person went into plastic surgery.

If your Ph.D. was related to the hrs complex then that person went into Neurology.

Am I getting close?

 

[Primate]

Several of us, err, them, have gone into industry and are PNG (persona non grata) at our university. More later. Gotta run...........

P

 

[SaltySqueegee]

Hi there fellow Doc-Scientists,

It has churned through the rumor mill at my institution that a new regional (East-Coast/Mid-West) meeting for Physician-Scientist Students is coming up this April 17th, 2005. Does anyone have any information on this?

As always, your thoughts and info are much appreciated,

-Salty

 

[BDavis]

Several of us, err, them, have gone into industry and are PNG (persona non grata) at our university. More later. Gotta run...........

P

Primate, do you think this attitude is specific for the MSTP graduates and/or a general attitude towards anybody who left academics for industry? What about MSTP graduates who chose private practice, are they also ostracized? I would imagine that career pathways of graduates is considered during the NIH review of the MSTP grant at a given institution, but I don't really know. Some academic faculty have very strong opinions about Ph.D.'s going into industry positions such as industrial post-docs.

 

[Primate]

My experience is that there are several tracks, some considered worse than others.

The worst is industry in a non-bench function (consultant, financier, marketer, manager, etc.).

Next is private practice. No MSTP program director likes to see his/her students doing face peels or silicone implants.

Next: teaching academic clinician. Not getting RO1s makes MSTPs unhappy.

Next is industry with some bench component (usually starting at the bench and moving toward directing a research effort). This one is getting close to acceptable, depending on the company and how the job is structured, but is still frowned upon. OK, this one and the previous one are close or even interchangeable.

Followed by: fair amount of clinic, some lab. Grant funding from smaller organizations in smaller sums, with publications going to 2d to 4th tier journals (but, thank goodness, some real publications).

Last and best: Hard core bench, with or without clinical responsibilities, lotsa grant $$ and publications.

Pretty sure that this is true of most MSTPs. Not so sure about MD/PhD programs outside the MSTPs. It makes sense that this is the preferred hierarchy, as MSTPs are reviewed every 5 years and what their grads are doing (grant funding, types of training programs they're in, etc.) is one of the metrics.

As I've also said on this forum, several times, that is also why the government ponies up the big dough to train combined degrees - they're hoping to get tranlational researchers and are willing to make the bet. In this sense, I don't think that program directors are misguided using the above general ranking. That said, most directors are also people and understand that some of their students will "drop out" and become, as it's specifically known around here, a "failure of the program," without holding any personal animosity toward the particular person. It's more a general hope that the students will do what they initially said they wanted to do when the university rolled the dice and funded them. Pretty fair, in the end.

I also think that some of the strongly held positions about industry not being the best choice for a post-doc (or an MSTPer) are derived from a strongly held belief that grads of the programs do indeed want careers at the bench, and that industry may have slightly different priorities which can derail a line of investigation if it doesn't show commercial promise, leaving a post-doc up the creek if they want to start a long term academic career. I think this can indeed be a problem, but I also know of many who want what industry offers without regard to returning to university (steady job, regular hours, decent pay in return for occassionally having to drop a project, even if it's scientifically interesting).

People aren't ostracized, I think, if they go outside the fold. It's more that once you're out, you're forgotten and have few opportunities to interact with the academics - and there probably is some dissapointment (professional and often personal) on the program directors' part when people don't follow in their footsteps. At least, there should be if the program director is invested in the process.

In the end, it all comes down to personal choice and doing what is right for the individual. What one may have wanted a decade ago may change, but one must remember that a program director is already differentiated and is looking for their scientific progeny to tred along the same fate map. Makes sense to me.

P

 

[Treg]

Here is my 0.02 about translational research-

I am finishing up my PhD, and my project is very applied. I work on transplant physiology/immunology using both human and mouse tissue in vitro and in mice. Most of the past four years has been spent doing typical grad school activities, going to basic "hard core" science seminars, meetings, journal clubs, etc. and thinking like a basic scientist in terms of my experiments. The purpose of my project is to improve a transplant procedure that was developed at my university. Over the past year, I have been attending the clinical study patient follow ups and transplant meetings, where they decide who gets listed, why/why not, how post-transplant patients are doing, etc. Seeing the other side of the equation, meeting patients, has been extremely inspiring for me. In the first few weeks I got more ideas for experiments than I got from a year of seminars. I have been more thoughtful in terms of finding ways to make my mouse experiments more "humanized" in terms of disease monitoring and treatment. Most of all, seeing the clinical outcome of years of basic science research have a positive impact on real people is amazing.

Based on all of this, I will be going to med school when I am done (<1 year, woo-hoo!), and I am looking forward to it. In the end, I hope to have a career where I do normal outpatient or inpatient consults one day a week, clinical research activities one day a week, and basic lab work three days a week. I have witnessed several docs with this type of schedule and they seem pretty happy. Also, at least at my school, they get paid the same as someone in their specialty who does 100% clinical. Anyway, I just wanted to say that I have thought a lot about this. Depending on where your research interests lie, the strengths of your institution, and your specialty, it can be done. I know that one of the transplant surgeons in our group does a ton of clinical work, clinical research, and has a lab. I see the guy in the hospital and he looks absolutely fried all the time. I know another guy who is GI doc who does clinical consults 4-5 weeks a year and the rest is basic science, and he is pretty mellow. And then there is my supervisor who is MD/PhD with no clinical activities since his residency.

Well, I rambled a bit there, but I hope some of it makes sense

Treg

 

[BDavis]

I think the outlined order of preference of career is very true for MSTP program directors especially when a NIH site review comes up. The career choices of alumni seems to weigh heavily in the grant. If concerns are raised during a site review, we certainly hear about it and the program quickly comes up with a patch to fix it (I think we are on v1.4 for our program now). However, I sometimes wonder if these adjustments are there to help our training or to merely appease the NIH reviewers. It is kind of like addressing some reviewers in papers; sometimes you just bite the bullet and do the experiment they designed (even though it adds nothing to your paper) to appease the editors.

For example, one of the concerns raised was that many of our graduates stay at the same institution for residency training. At a first glance, I guess you could assume that our graduates could not get in anywhere else and that is why they stay at the same instiution. However, I think one of the reasons is that the M.D./Ph.D. is a long committment (7-10 years) and often one gets married/have children/buy a house so there are external factors that might influence where one chooses to do their training. Nonetheless, we are encouraged to look at other programs outside our home institution.

Despite the pressures to fight for NIH funded spots or maintain the same level of funding, I feel that our program director has been pretty good about giving us a choice between all the different career choices whether it be private practice, industry or academics. He doesn't seem to mind inviting speakers that have followed alternative pathways other than academics. Each MSTP probably have different personalities and internal objectives. I do find it odd though that our program does not always actively encourage our graduates to do a residency (and some faculty actually discourage doing a residency) and perhaps this will change in the future. I guess people try to influence you to follow a career path that is in their best interests or perceived to be your best interests.

 

[b&ierstiefel]

Am I getting close?

Yep you are

I met both of them at that Aspen conference I went to (I think it was back in 2000 or 2001). It was the year after that when a whole bunch of you guys came to the conference.

As I've been to that meeting 3 times during my graduate phase of training, I have to say those meetings were a blast. I miss going to them; I tried scamming a ticket from the program to go last summer at the start of my M3 year but that was a no-go