medicinal chemistry PhD as part of mstp

[CMVpromoter]

Currently, I'm planning to do a PhD in medicinal chemistry, maybe MSTP.

Do you know many mstp'ers doing this combination? How common is this?

At my school, I've found only one student so far who is doing a PhD in pharmacology... none for medicinal chemistry so far.

How difficult would such a path be, since medicinal chemistry is very basic/physical-chemistry heavy?

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[friendlybear]

Hi, I thought I'd offer some advice since I have worked in a medicinal chemistry lab for 1 year and know many friends in chemistry as graduate students. I am assuming you will be engaging in wet chemistry; as for computational medicinal chemists, I really don't know.

Medicinal chemistry nowadays is largely focused on 2 things: total synthesis of natural products, or synthesis of a large number of analogue compounds designed as agonists or antagonists for a specific target (usually an enzyme people have found to be really important, like HIV protease for example). Organic chemistry will be your main tools, and it's really a time consuming area of work: reactions (sometimes overnight or 24-47 hours), column chromatography, evaporating solvents by rotavap, plus the reactions that you have to re-run and redesign because they didn't work. At shortest, a PhD can be granted in 5 years for medicinal chemists; at longest, I have had 3 friends graduate in 7.5 years. Really depends on your boss for that, and maybe the MSTP can help you shave that down. From my experience, the work required for finishing a PhD includes a large number of synthesized compounds (that show potency and affinity in binding to the target, otherwise it's not good enough for publication) and a total synthesis, or it can just be total synthesis of 1 or 2 compounds. A total synthesis by an experienced graduate student can sometimes take 2+ years to finish, and longer for the entry-level student.

However, you will be aided by a lot of good chemical literature where reactions have already been established by others for you to apply to your specific synthesis. I think organic chemistry involves a lot of patience for success, simply because it just takes longer to do everything. It's OK, this gives you a lot of time to think about your projects! Medicinal organic chemistry can be quite fun. I enjoyed it very much.

 

[QofQuimica]

Do you know many mstp'ers doing this combination? How common is this?

I'll leave this question for someone else to answer, as I did my degrees separately (MS in med chem and PhD in pharmaceutical chem, followed by MD).

How difficult would such a path be, since medicinal chemistry is very basic/physical-chemistry heavy?

This question is impossible to answer without knowing what you mean by "difficult." Do you mean difficult in the sense of getting a med chem PhD as part of an MD/PhD program, or difficult in the sense of med chem being an inherently difficult subject to learn? If you're asking about the logistics of doing a combined program, again, I'll defer to those who are more in the know than I am.

If you're asking how difficult it is to learn the subject, I would say that it's not inherently more or less difficult to learn than any other applied natural science. FYI, med chem is actually more analytical chem-heavy than p-chem-heavy. Although I had to take a semester of physical organic chem during grad school, I did not have to take grad-level p-chem. However, I did take a year of grad-level analytical chem (one semester of NMR techniques, one semester of general analytical chem).

Just to clarify what the previous poster said, total synthesis of complex structures like natural products is not generally the kind of work that medicinal chemists would do. In fact, complex natural products are not very good targets for medicinal chemists because there would usually not be an efficient way to synthesize large quantities of them, should a promising potential drug be found. The guys and gals who do natural product synthesis are hard-core synthetic chemists who try to synthesize technically difficult structures in order to develop new synthetic techniques, and also because they like the challenge.

In contrast, the goal of med chem synthesis is much more practical. Basically, you want to synthesize a library of related compounds that can be tested in an assay to assess each compound's ability to affect a desired target (often to inhibit a biologically important enyzme). The purpose of doing this is to delineate a structure-activity relationship that can then be used to design a new library of compounds with greater potency, ideally to the nanomolar level or less. Ideally, you will complete this synthesis in as few steps and as high of a yield as possible, again with the expectation of being able to scale up production if you find a good candidate. If you're in a well-funded lab, like in industry, much of the synthetic and purification work can be automated. Our lab had a robot; I'm sure the machines in current use are much nicer than what we had over a decade ago.

As the previous poster mentioned, some med chemists also perform computer-assisted design of compounds. This involves trying to fit pieces of molecules (organic groups) into the active site of a crystal structure of an enzyme. The goal is to have the computer calculate the structures and configurations that would maximize the decrease in free energy due to the changes in entropy and enthalpy that occur when small molecules bind to a protein. The success of this technique requires having someone who is knowledgeable about synthetic techniques, as the computer is not smart enough to know which compounds are actually technically feasible to synthesize in the lab.

Hope this helps, and best of luck.

 

[friendlybear]

Thanks for expanding this topic, QofQuimica! The lab I worked in had a robotic HPLC, but no robot for doing reactions for us. Your adviser actually had one of those? Impressive.

 

[flashback]

The general idea of doing research that is heavily basic-science oriented as an MD/PhD has been something I have really been struggling with (nearly ripping my hair out about) for the last half a year.

Like you (I'm assuming), I love chemistry and looking at processes at the molecular level. I want to do research related to drug design and development.

The problem is that this work really does not interface with patients unless you manage to bring a drug to clinical trials. Your patients are not going to (significantly) contribute to your lab work, and visa versa. Everyone will tell you that having research interests that are along these lines is not ideal for an MD/PhD and they're probably right.

I managed to convince myself that because I was interested in drug development, I would do a PhD in pharmacology for the sake of working with patients. 4 months later.... I'm realizing that was dumb. First and foremost, do research that you know you will love. (I know you didn't saying anything about Pharm, but don't fall into the trap that I did- drug discovery and pharm are very different fields)

The truth is, if you want a strong med chem background, any MSTP is likely not going to be your best option. Unless you foresee yourself getting into a few of the top 10 mstps then odds are you will get a better education elsewhere going straight PhD. You'd be much better served going to a place like Scripps (and odds are if you're very competitive for MD-PhDs, you'll be a shoe in there).

If you go the route of the MD-PhD with research that isn't exceptionally translational, one of my mentor suggested you will have the following benefits: 1. It will be easier for your to stay focussed on research that is medically relevant and important 2. You learn the special MD-handshake.

As will likely be the case with you, I know that I will be interfacing with people who do clinical trials, etc. so I think the MD will be helpful there. However, if you want to see patients, you're losing time that you could be doing research and writing grants and you're going to be spreading yourself thin.

The way I see it, here are some of the pro's and cons of going into research that is basic science oriented. Many people may disagree with me, and be wary of my advice as I'm still a senior in undergrad.

PhD Only

Pros: Better research education, you will have your pick of school (likely)
A career focussed only on research
PhDs will not call your PhD a "baby PhD"
You will probably save 2-3 years compared to doing an MD/PhD. You may save even more years depending on what residencies and/or post-docs you may do.

Cons:
You will not be able to see patients.
You will not have the same extensive medical education as an MD
MD's will not take you seriously and you will think they are stupid
A career that is potentially more cut-throat (MD-PhDs always have clinical work as a backup plan)

MD/PhD
Pros:
You will have an awesome science and clinical education
You can work with patients
You have more career opportunities and more financial security- if your research career bombs, you can always go to private practice.
(If you believe the experts) you will direct your research in more efficient ways.
You will be able to communicate well with MDs as well as PhDs
You will be awesome at writing grants- ask anyone in the basic sciences, if they want a grant funded, they pretty much have to provide some health-related reason that their research is important

Cons:
You're setting back your career 2-3 years PLUS a residency (if you want to see patients)- okay this isn't completley true, as a PhD you would do a Post doc which would likely be shorter though.
You're PhD is likely not as thorough as a PhD-only (plan on a post-doc or research oriented residency at the least)
Although probably making more than a PhD, that will be at the expense of spending time in the clinic and away from the lab.

 

[URHere]

I'm an MD/PhD student completing my PhD in chemical biology, and I'll take a crack at answering some of your questions.

As for how common this path is...both of my rotation mentors have told me that is an extremely uncommon field of research for an MD/PhD student. One of them suggested that there are only a handful of practicing MD/PhD chemists in the US...which can be a good thing from the perspective of finding a position post-graduation, or a bad thing in terms of how unpaved the path is likely to be. As for completion time, I can only guess (there aren't enough of us out there to really get a solid time estimate) that 5 years would be the approximate PhD time for a lucky MD/PhD. I've been told by many PIs here that it takes an average of 2 years to become a solid chemist...the other 3 years (or more) are for the thesis.

One thing I do want to stress about the medicinal chemistry path is that most labs you are likely to find associated with a hospital will not focus entirely on synthesis, or creating novel drugs for selected targets. Instead, many labs (like mine), choose to modify existing drugs to circumvent drug resistance or to minimize side effects. This means that the synthesis times are generally much shorter (weeks), and that the same reaction technique can be applied to a number of compounds, which saves time.

The fact that the chemistry is directly applicable also means that many labs conduct their own in vitro and in vivo experiments along with the synthesis- this means that if your synthesis with one drug is lagging, there is always some other test you can be doing with another compound to move your thesis project along.

Although people might argue that chemistry research is not a good fit for a physician scientist, I disagree. Unlike the time-sensitive experiments that overrun biology, chemistry is far easier to fit around a schedule. In most cases, it really doesn't matter if a reaction runs for 24 hours or 48, and there is no need to get up and work with your chemicals at a certain time of day. That may not matter much to a PhD student, but I imagine it will matter a great deal once those students graduate and are attempting to maintain their clinical and lab skills simultaneously. Chemistry is also broadly applicable and can be easily modified to fit most given clinical fields. All in all, I think it's a good fit for an MD/PhD, and I'm very happy with my choice thus far.

However...if I'm still in lab 6 years from now, I may reconsider...

 

[nothingman]

I've also just finished my PhD in what could be described as a chemical biology lab (that did a fair amount of med-chem as well). My undergrad training was in mechanistic organic chem, though my PhD thesis was a mix of crystallography, peptide biochemistry, and a bit of small molecule chemistry. I finished in four years and hope to continue some form of chemical biology/biophysics research in my post-medical school training. There were two other MD-PhDs in our lab; one with a very med-chem heavy project (with previous o-chem work in undergrad) finished in three years, the other one's project is taking somewhat longer.

If you have a deep interest in this field (protein-small molecule interactions, chemical biology, med chem) and just like seeing the world of science from an atomistic/molecular, 3D perspective, AND love taking care of patients, I think the MD-PhD is a reasonable, although as mentioned above, poorly trodden path.

I have certainly found that other faculty working in this field were/are poorly represented in our MD-PhD lectures/mentorship programs/grand rounds and clinical departments in general. However, in talking to several research residency/research-clinical fellowship directors, they seemed very open to allowing one to do further training in this field, even if it involved working outside their department and in a basic science lab in say a chemistry department. The only requirement was a loose association/applicability to the clinical specialty, but nothing specific. Thus, it seems like that community, at least in some fields, would support such a way forward. As was mentioned before, there are few MD-PhDs with such training, but this could be a good niche if one finds the right place. Certainly, the chemical biology skillset is somewhat unique.

A few more thoughts:
- Especially if applying MD-PhD, go to a place with good labs in this field and with a program that will allow you to work there (some have more red tape than others especially between school of medicine/arts and science programs). Strong basic science departments at Scripps, UCSF, Penn, Harvard, Wisconsin, many others.
- It seemed like a chemistry (vs. a biology) background was an advantage when applying to MD-PhD programs, for reasons that are not fully clear to me... relative rarity? bias for "hard science?" Not sure.
- If you join such a lab for your PhD and have a goal of getting out fairly quickly, be very careful with your project selection. As mentioned before, these tend to take a long time, especially if structural biology is involved. Have something safer going on if crystallography/structural NMR or very difficult multi-step synthesis is in the picture.

Feel free to PM if I can help in any way.

 

[whiteshadodw]

i actually had a talk about this with my mentor about this today. as i also hope to be doing some sort of drug discovery as an MD/PhD. in a nutshell:

1. drug companies can screen through 1000s of compounds either in vitro or in silico. the issue is is that if you are doing in silico stuff, some of compounds that you get hits for might be ridiculously difficult to synthesize. no drug company is going to want to synthesize something that takes forever, costs a lot, or has low yields.

2. i know an MD/PhD at our university who actually does in silico drug design, and i told my mentor that i was interested in drug design because of this MD/PhD that i met. i was always interested, i just didn't know how to go about pursuing this path (hence the reason i was speaking to my mentor). this MD/PhD was able to pull off this in silico design for two reasons. a, the patients he had access to just didn't respond to any of the drugs currently on the market (ie, gleevec). b, he had a great structural biology background. this was important because the computer program he was using to screen compounds was just a computer program, he understood the structural biology behind everything in this program. even then, the compounds he found in silico might not even make an animal trial because of the logistics in the synthesis.

 

[CMVpromoter]

OK, so it seems that many people think a medicinal chemistry PhD may not work well with an MD.

So for those who know, how hard is it to get a job with a PhD in medicinal chemistry? How's the job market?

Thanks for all the replies.

 

[friendlybear]

Well, people are getting laid off in significant amounts right now in the Pharma industry. Eli Lilly recently laid off thousands of people, including medicinal chemists, Pfizer laid off 19,000 people so it could acquire Wyeth, and many Wyeth people will most certainly, if not already, have layoffs. PhD chemists are being hurt in this process as well.

 

[flashback]

PhDs are unfortunately "a dime a dozen." The degree itself doesn't mean much. From my understanding, the reason for this is excessive training grants from NIH in the past. In any case, no one will argue that there are way more PhDs than appropriate jobs available. To help prevent yourself from ending up like many PhD's today (unemployed) you really need things that are going to separate you from the rest. My advisor's PhD-only advice is to only go that route if you're going to be in one of the top 6 programs. There's a pretty dramatic difference between the top 6 chemistry programs and pretty much anywhere else. He's a bit of an elitist... but it's kind of true depending on what your aspirations are. If you want a good chance a being tops in research (academics or industry) you're going to need a big name behind you and/OR excellent PhD publications. Considering how much of a crap shoot research can be, going to the most prestigious place possible is going to be your best bet for a secure future career. In no way will that compensate for poor publications during your PhD, but it will buy you substantial credibility. I don't think many caltech PhDs find themselves out of work .

I guess one of the +'s of the MD/PhD is that an MD actually does mean something (assuming its not from the caribbean ). At the same time, if you're set on a top-notch chemistry degree, there are probably a total of 25 MD-PhD slots at those top places (for ALL fields of science) so no matter how awesome you are, there'e absolutely no guarantee you'll get in to any of them.

PS. The schools with MD-PhDs I'm referring to would be Stanford, UC Berkeley (via USCF), and Harvard. Caltech, MIT, and Scripps of course don't have MD-PhD programs.. Scripps will one day but that's awhile off.

 

[whiteshadodw]

Caltech and MIT are involved in MD/PhD programs though they may not have one. if you get into the UCLA program I think you can do your PhD at Caltech, and if you get into Harvard's MSTP you can your PhD at MIT i think. check the programs' website out.

 

[nothingman]

I also thought that one could do research at Scripps while in the UCSD combined degree program. Don't know if that has changed recently given the aforementioned plans at Scripps. UCSD's MSTP website appears to indicate that this is still the case:

http://meded.ucsd.edu/asa/mstp/research_opportunities/

 

[QofQuimica]

So for those who know, how hard is it to get a job with a PhD in medicinal chemistry? How's the job market?

It will depend on what kind of job you're looking at, but as flashback suggested, there are more PhD chemists than there are jobs for them all.

One common option is to work as a chemist in industry. The number of positions for PhDs is limited compared to MS or BS level chemists. In fact, you may be better off stopping with an MS if going into industry is your goal.

Many people post doc after finishing grad school, usually in academia. (Industry post docs are also available sometimes, but this is much less common.) Post docs are generally new PhD grads who work as junior scientists under an established senior scientist (PI). Getting a postdoc is generally not difficult; I've never heard of anyone not being able to get one. On the flip side, it is not uncommon for people to complete 2 or 3 post docs before being able to get a permanent job (i.e., tenure-track at a university), if that's their goal. Some people never get a tenure-track job. They may become research associates (full time researchers who don't run their own lab).

Teaching is another option. Some of my friends from grad school taught full-time after finishing their PhDs. If you want to teach college students full-time and not do research, you can possibly dispense with doing a postdoc. It seems like organic chem instructors are always in demand. Hey, there are a lot of premeds out there, and they all have to take a year of organic chem from someone.

Then there are some more unconventional jobs, like working for the government, armed forces, patent office, science writing, etc. Offhand, I can't think of anyone I know who went down one of these paths, so I can't really comment about how hard it is to get one of these jobs.

 

[achamess]

Hey all,

This is a great thread and I'm glad the OP started it. Lots of good info here.

So for a while I've had it in my mind to do the PhD portion of my MD-PhD in chemical biology. I've always had a fascination with chemistry, particularly organic synthesis, and throughout my UG research and now, I've tried to apply my enthusiasm for and knowledge of chemistry in a biological context.

As others have said, it is true that there are few examples of MD-PhD chemists, but they do exist. I know because I work in the lab of one If anyone wants a few examples, PM me. I imagine that students have not chosen chemistry for their PhD because either a) they didn't want to do any more chemistry, or b) they didn't think the skills and knowledge they'd get from such training would be applicable to their future research pursuits.

I think more and more, students are recognizing that receiving formal training in organic/medicinal chemistry is an excellent path for someone striving to make contributions to medicine or basic science. I've met quite a few students on the interview trail this year who have expressed an interest in chemical biology at least, and I've met some current MudPhuds who are doing their PhDs in chemistry departments.

For me, the appeal of having a chemical background is that it will give me insights on an atomic/molecular level that I can apply to biological problems. Importantly, it expands the arsenal of tools at my disposal that I can use to probe biological questions, hopefully giving me the ability to bring a fresh perspective to problems already exhausted by traditional methods. Expertise in organic synthesis, pharmacology and medicinal chemistry is highly practical for a physician-scientist, I would think, given that the major line of therapy for most medical problems is some kind of small-molecule drug, and recently, antibodies or RNAs. I've made this argument several times on the interview trail, and I haven't gotten any flack for it.


In the end, I'd say, if you want to study chemistry and you think it will help you later on in your career, go for it. I'm going to do it Studying chemistry won't preclude you from doing biomedical research, but doing a strictly biological PhD might preclude you from doing chemistry later on. I think chemical biology is ideally suited for MD-PhDs with an interest in chemistry but in the context of biology.

 

[ChemMed]

For me, the appeal of having a chemical background is that it will give me insights on an atomic/molecular level that I can apply to biological problems. Importantly, it expands the arsenal of tools at my disposal that I can use to probe biological questions, hopefully giving me the ability to bring a fresh perspective to problems already exhausted by traditional methods. Expertise in organic synthesis, pharmacology and medicinal chemistry is highly practical for a physician-scientist, I would think, given that the major line of therapy for most medical problems is some kind of small-molecule drug, and recently, antibodies or RNAs. I've made this argument several times on the interview trail, and I haven't gotten any flack for it.

I am currently finishing a PhD in medicinal chemistry and have absolutely no regrets, but I caution the MD/PhD who would choose this route. The very nature of this PhD can be very time consuming. It is very common for PhD students to stay in these programs up to 7 years. I'm not saying this will be you. In fact it wasn't me, I'll be completing mine in four, but it is something to remember when choosing your program. Additionally, there are many faculty in medchem programs who do plenty of biological work in addition to chemical work. These potential advisers could require a shorter time commitment to the PhD portion of your program. I personally would not have done any other PhD. I have covered structure biology, structure activity relationship studies, high throughput screening and chemistry. All of these learned areas will only benefit me later. Good luck with your choice.

 

[Chemdocx]

during my PhD I developed a new chemical reaction that could be pulled off in biological solutions/cells/lysates etc.I think chemistry is one of the better things to get a PhD in with the MD/PhD. You can make most anything then test it out.

 

[achamess]

during my PhD I developed a new chemical reaction that could be pulled off in biological solutions/cells/lysates etc.I think chemistry is one of the better things to get a PhD in with the MD/PhD. You can make most anything then test it out.

Good point chemdocx. Did you do some kind of bioorthogonal reaction develop, i.e. some kind of click reaction?

 

[Chemdocx]

I wish I had invented the click reaction. But the reaction is bioorthogonal.

 

[achamess]

I wish I had invented the click reaction. But the reaction is bioorthogonal.

Haha, don't we all. I was suggesting maybe some variation of a 'click-like' reaction. But anyway, good stuff. Look out for a PM from me.

 

[HolyCow0333]

Wow CMVpromoter and flashback, I felt like I was reading my own posts!
Likewise, I'm interested in getting an MD/PhD in chemistry or medicinal chemistry, but only if I can do basic drug design research. I've been working in an organic synthesis lab synthesizing and diversifying drug-like compounds, and I love it, but if I can't do basic research with an MD/PhD, then I'd just go the MD route since I know I like the clinical aspect of medicine (yet can't see myself doing clinical research, go figure). Any advice for someone who'd choosing between MD and MD/PhD?

 

[miz]

An MD/PhD isn't just 8 years, it's really a full lifetime (8+4+4+5=21); you're probably around 21-22 right now. You'll be twice as old before you're in a position to get tenure. This is the single biggest thing I wish I had known before I chose to pursue an MD/PhD.
(8 training, 4 residency, 4 fellowship OR postdoc, 5 tenure-track) all to be an associate professor.
I am actually still pretty suited in personality to this track, but a few students in my program are beginning to realize that they do not feel the same way. Mostly it's hard to have kids without lots of support.

The biggest misconception I see is that students think that after training, an MD/PhD divides time between medicine and research equally. I don't think this is true except in rare cases.

I'm in chemistry, but I have never seen it as unusual and there are a number of other students in my program studying chemistry or chemical biology...not sure what you're asking there. many programs encourage MSTP students to study basic research; none encourage them to do clinical only; some emphasize a translational 'bench to bedside' approach. No program will discourage you from doing a purely basic PhD. The general NIH vision for the "MD/PhD career path" includes some kind of translational research, but that is many years in the future and there is nothing to stop you from pursuing a basic-only career except, why would you need the MD to do that?