科学网-随笔：如何在科研上成功（Part I）

Essay: How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge
Jonathan W. Yewdell1
Abstract
Biomedicalresearch has never been more intellectually exciting or practicallyimportant to society. Ironically, pursuing a career as a biomedicalscientist has never been more difficult. Here I provide unvarnishedadvice for young biomedical scientists on the difficulties that lieahead and on how to find the right laboratories for training in theskills that you will need to succeed. Although my advice is gearedtowards succeeding in the United States, many aspects apply to other countries.
Ifyou are contemplating pursuing a career in the life sciences, or havealready embarked on one, you need to give some thought to your careerprospects. So, take a study break, grab a cup of coffee and read on.
Unfortunately,I need to begin with some depressing facts. First, only a smallminority of Ph.D. students will ever have opportunities to becomeprincipal investigators (PI) in academic settings and direct their ownindependent research programmes. Second, even if you are among thiselite group, the odds are that you will be well down the path towardsretirement by the time you receive your first research project grant(R01) (the average age is 43) from the National Institutes of Health(NIH), the principal source of funding for biomedical research in theUnited States. Third, for your entire career as a PI, you will putinordinate efforts into writing grants. If you should ever losefunding, you will be at the mercy of your institution for yourcontinued employment. Fourth, if you do achieve the ‘Holy Grail‘ offull professorship then you will not be poor, but you will be far worseoff financially than nearly all of your peers who have similar levelsof talent, energy and dedication, but who chose other careers.
The number of doctorate degrees awarded per year in the United Statesin the life sciences has increased more than threefold since 1966,whereas the number of tenured scientists has decreased slightly from apeak in 1981 (according to National Science Foundation data3).Consequently, in the past 25 years the fraction of Ph.D. holders withacademic independent investigator positions has decreased steadily. Thefraction of Ph.D. holders with tenure or tenure-track position is now30%. Graph reproduced from Ref.3 © (2007) FASEB.
Yourprofessors might tell you that this is the way it has always been, butthis simply isn‘t true. Twenty-five years ago the situation was muchrosier. Scientists gained independence a decade earlier and funding,although never easy, was more reliable and accessible. Universitieswere more humane institutions where accountants had less influence overinstitutional priorities and decisions. Our current lamentablesituation is fixable, and will have to improve significantly if the United Statesis to maintain its position as a leader in science and technology. Apositive outcome is not guaranteed, however, and fixing the currentmess will require the concerted efforts of scientists, universitypresidents and politicians to save the biomedical goose that has laidgolden eggs for US biotechnology and health care for the past 50 years.
Science rocks
But there is good news too. Society desperately needs your talents. The future health, wealth and even survival of Homo sapiensdepend on a deeper understanding of the laws and mechanisms of natureand on using this information to develop new technologies andtherapies. For rationally thinking people with an altruistic bent, lifecan be no more rewarding than when practising the scientific method forthe benefit of all of the denizens of this fragile planet. As a buddingscientist, you are trained to expertly use the scientific method. Thatis, you learn how to wield the body of techniques that are used toidentify and investigate natural phenomena by formulating andrigorously testing hypotheses. The origins of the scientific methoddate back at least 1,000 years, and it is arguably the most importantinvention of civilized man. Armed with the scientific method, we canexplore and understand nature to the limits of our intelligence. As ahigh priest of ‘Scientific Methodism‘, you will be equipped for successnot only in science and its allied occupations, but in virtually anycareer that requires rational decision making (and in some, such aspolitics, that ought to).
Moregood news: for individuals with a hunger for knowledge and aninsatiable curiosity about how things work, science offers a constantchallenge and, best of all, the intense thrill of discovery. What canmatch being the first person who has ever lived to know something newabout nature? And not just the big, infrequent, paradigm-making (orbreaking) discoveries, but the small, incremental discoveries thatoccur on a daily or weekly basis too. If this doesn‘t give yougoosebumps and if you are not in a rush to get to the laboratory in themorning to find the results of yesterday‘s experiment, then you shouldseriously consider a non-laboratory career. Making discoveries is thecore reward for the myriad of difficulties you will face in yourscientific career (see Part II, in which I discuss making discoveries1).Although it is possible to succeed in science even if you lack thispassion for discovery, you will almost certainly be miserable and makeyour colleagues, friends and family wretched too.
Sciencehas other perks. Contemporary science is one of the most communalactivities ever pursued by humanity, and is among the mostinternational careers possible. You will probably be interacting on adaily basis with scientists from all over the world, both in yourlaboratory and over the internet. Once established in your career, youcan fly to dozens of cities across the globe and be greeted by acolleague that you either know personally or through reading eachother‘s publications. You might even train a generation of researchersin your laboratory who will disperse around the globe to pass the torchof the scientific method to the next generation of their nation.
Thisgenerational transfer of Scientific Methodism is, in fact, the mostimportant and tangible achievement of a scientist. Discoveries are thejoy and stock of our trade, but when your career is over (and probablywell before this moment), few people will remember your brilliantpapers. If you are successful (and lucky), you will have contributed afew lines to text books that future students will resent having tomemorize. Through no fault of your own, and for reasons that you couldnot have anticipated, your discoveries might prove to be the artefactsthat led your field in the completely wrong direction. You will behappiest in science if you are content with pursuing the truth to thebest of your abilities and in passing the skills and insights you havedeveloped to the next generation. Scientists who pursue fame aredestined to be forgotten and forever dissatisfied with theirachievements. In practical terms, peer recognition is needed only tomaintain funding and to attract talented individuals to your laboratorywho will make your daily laboratory life more productive and enjoyable.Beyond this, chasing fame is a waste of time that could be better spenton science itself, or on enjoying life outside the laboratory.
Getting started: graduate school
Choosing a graduate programme.Choosing a graduate school in which to pursue your Ph.D. should belargely based on the field that you would like to enter. Obviously, youshould choose a programme that has a well-respected faculty. Sizeprovides a large number of advantages, including a larger number ofpotential mentors to choose from, more students and postdoctoralfellows who can become lifelong friends and colleagues, better chancesfor collaboration, greater access to reagents, techniques andspecialist equipment, and a more exciting intellectual environment. Tominimize the insanely long ‘training‘ period of your career, you shouldfind a programme that takes pride in expeditiously awarding Ph.D.degrees. It should take 4 or 5 years for a decent student to finish aPh.D., with an absolute upper limit of 6 years. Any longer than thisand the student is either not suited for science or is being exploitedby the mentor. Also, choose a department where the current Ph.D.students are treated as junior colleagues, with an eye towards theircareer development, and are not just exploited as inexpensive labour(small departments can be better in this respect).
Choosing a laboratory. Once you have chosen a school (or vice versa) to work in, your most important decision will be to choose a laboratory. The decision can be based either on the topic of research or on the mentor. I would strongly recommend the latter (Box 1). Good scientists work on interesting and important topics, so a good mentor has this covered. Your goal as a graduate student is to become an expert in wielding the scientific method, and this can be achieved pursuing any project. The topic matters most in the types of experiments it entails. A good project will enable you to design, perform and analyse experiments on a routine basis, ideally several per week, if not daily. This provides the best training and, importantly, is also the most fun. This will also develop your abilities to conceive the crucial controls that are needed to interpret the data in a meaningful way. ‘Control creativity‘ is a central part of your scientific IQ; it comes only from the experience of designing and interpreting experiments. You should avoid projects that are largely based on using a single technique to develop a reagent or collect data (for example, generating a transgenic mouse).
Choosing a mentor. Although there is tremendous subjectivity in choosing a compatible mentor, there are a number of objective criteria. Are the people in the laboratory happy and enthusiastic about their research? Have former students gone on to productive careers? Does the mentor treat students as junior colleagues and not as employees? Generally speaking, you should run from laboratories where a PI is referred to as Doctor X and not by his or her first name.
Frequently,you will have to choose between a small laboratory with a newinvestigator versus a large laboratory with a well-establishedscientist. Newly minted assistant professors will not have much of atrack record as mentors; you might even be the first student theytrain. Still, you should seriously consider joining such a laboratoryif the chemistry seems right. Although this has its obvious risks, youare a much more valuable commodity to a small laboratory, the survivalof which could well depend on your personal success. Consequently, youwill get more intense mentoring and will probably be workingside-by-side with the PI. The best situation is to be the first Ph.D.student of a rising star, for you will be maximally productive, willgenerate well-developed ties to your field and will have an influentialchampion for years to come (although because academic ‘star‘ formationis an inexact science, this often takes some luck).
Skills, not papers.Contrary to what you might have heard, it is not critical to have aspectacular publication record from your Ph.D. When the time comes toapply for a tenure-track job, the selection committee will focus on theproductivity and promise you displayed during your postdoctoralfellowship. Furthermore, a solid Ph.D. with one good first-author paperthat is based largely on your own work is all that is usually requiredto obtain the postdoctoral position of your dreams, particularly forcitizens of the United States,who are in short supply at this level. Your focus as a graduate studentshould be to develop all of the skills you will need to be anindependent scientist.
Atsome point as a graduate student you will need to take responsibilityfor all aspects of your career and develop the skills of an independentscientist. You need to develop confidence in your ability to makediscoveries and learn new techniques, so that you will not be limitedlater in your career when your findings lead you to new and unexpectedareas (see Part II (Ref1)).You need to do the background reading to place your results in theirproper context and determine the next step in the project. You need tolearn how to present a seminar in which you convey not only the dataand conclusions, but also your depth of knowledge and enthusiasm foryour field of research. Such public-speaking skills are critical forpeer recognition of the impact of your research, for recruitingstudents and fellows to your laboratory, and for effective teaching.Most importantly, you need to learn how to write concisely and lucidly2, for without this skill, you will not be able to raise grant money or place your papers in high-impact journals.
Step two: postdoctoral fellowship
Inmany ways the most important decision on the PI career path is whereyou do your postdoctoral fellowship. It should be in a field in whichyou envisage starting your independent career, the success of whichwill be almost entirely dependent on your ability to attract funding.As a newly independent scientist, study sections will be loath to fundyou to embark on a project that is not a direct continuation of yourpostdoctoral studies. This also means that you will need access to thereagents you developed as a postdoctoral fellow. You will also need theblessings of your mentor and, optimally, your mentor should activelysupport your nascent career. So, in choosing your postdoctoral mentor,it is critical to determine whether a mentor enthusiastically supports,both materially and psychologically, the careers of their fledglings.This is easier to determine if the mentor is an established scientistwith a pedigree. Established scientists will also be able to offerlaboratories with a greater variety of expertise, reagents and greaterfinancial resources, all of which will help you establish anindependent line of research for you to parlay into an independentcareer.
Itis essential to visit the laboratories that interest you to gauge theproductivity, independence and happiness of the students andpostdoctoral fellows. It is a good idea to contact scientists who haveleft the laboratory to obtain their honest opinion of their experience(in laboratories headed by evil mentors, this might be the only way toascertain their pathology, as the current laboratory members may be toointimidated to express negative opinions). If the laboratory won‘t payyour travel expenses, then this does not augur well, as it indicateseither limited financial resources or stinginess. All things beingequal, it is advantageous to work at larger, wealthier institutionswhere there will be better access to expensive, state-of-the-artinstruments and core facilities, greater overall intellectual ferment,more laboratories for collaboration and a better chance to impressother established scientists, who can write the crucial recommendationletters for getting your tenure-track application into the interviewround. Sometimes, however, all things are not equal, and if the bestmentor is at a smaller institution, this will do just fine.
What is it going to take?
Perspiration.Success in science will require a major commitment of your body andsoul. As a graduate student, you should be spending a minimum of 40hours per week actually designing, performing or interpretingexperiments. As there are many other necessary things to do during theday (for example, reading the literature, attending seminars andjournal club, talking to colleagues both formally and informally, andcommon laboratory jobs), this means you will be spending 60 or morehours per week in science-associated activities. The key to success andhappiness is that most of this should not seem like work. If thelaboratory is not the place you‘d most like to be, then a career as aPI is probably not for you. At the postdoctoral level you will have towork at least as hard, but your most intense effort will actually beginas a tenure-track faculty member, when you are expected to fund yourresearch (and at least some of your salary too), teach undergraduatesas well as graduate and professional students, serve on committees andrun your laboratory, which itself entails learning an entirely new setof skills (such as accounting, diplomacy and psychology). Ironically,you will have more to learn as a fledgling professor than as apostdoctoral fellow. Until you are well into your career, there will betime in your life for just one additional significant activity (family,active social life with friends, a sport or a hobby), but probably notfor much more than that.
Talent.Enthusiasm and effort are necessary but not sufficient for a successfulscientific career. Talent is a key part of the equation, and at somepoint in your career (not necessarily as a graduate student), you willneed to objectively assess your skills and potential relative to yourpeers. The inexorable weight of the scientific career pyramid squeezesout all but the most talented from getting the tenure-track job thatwill offer you the chance of establishing your own laboratory.Furthermore, the insanely competitive funding situation is making thepreviously safe transition between tenure-track and tenured professor afar dicier proposition. Scientific talent is not a single parameter,but a complex mix of innate and learned skills and abilities.Deficiencies in one area can be offset by strengths in another. Somescientists achieve success by their experimental skills or insights,others by their management or political skills. There is no one path tosuccess and each successful scientist has unique combinations ofstrengths (and weaknesses).
If,for whatever reason, you decide that you are better suited for lifeoutside the laboratory, there are numerous career alternatives. Neitheryou nor your mentor should consider this outcome a failure. It isunfair, and even irresponsible for mentors to expect trainees toemulate their own career paths. Each mentor has only to train a singlereplacement to maintain the PI population at equilibrium. Even withrobust growth in NIH-funded biomedical research (which is unlikely inthe foreseeable future), the current investigator-to-trainee ratiodictates that most trainees will pursue careers that differfundamentally from those of their mentors.
Networkingplays a key part in providing information about potential alternativecareers and in landing such jobs. Alumni of the laboratories anddepartments you have worked in are the most proximal source ofnetworking partners. E-mail has opened a great portal into the academiccommunity for initiating contacts that can be deepened by follow-uptelephone conversations. It can be difficult to penetrate the corporateworld by this path, but conferences provide ideal circumstances formeeting scientists out of the academic mainstream who can provideinsight, advice and even job opportunities. It might be possible duringyour postdoctoral fellowship to develop your skills and attractivenessto potential employers by moonlighting or volunteering in the careerpath you are contemplating.
Final thoughts
So,your cup of coffee should be finished by now. Please don‘t bediscouraged, but give some thought to your career path. If you aretalented and passionate, you will have a good chance of becoming a PI;particularly in the United States,which still provides great opportunities for truly independententry-level positions. If the trials and tribulations of being a PIaren‘t for you, there are many other ways to use your scientifictraining to make a decent living and a valuable contribution tosociety. Now get back to work.