Lessons from a study section

First, some news: I was told last week that my promotion to full professor was unanimously approved by the faculty council (yay, me)!!! The promotion still has to be approved by the dean, but it seems likely. It felt really nice in itself as a validation of years of work…but also, my Division chief told me that my letters of support were glowing, and that meant a lot because the people who wrote those letters were leaders in my field. As I told my chief, their glowing letters said as much about them as people as about me, but still it felt good. Celebrations have been made, champagne has been drunk. I have to watch it though…a good friend has noted that I already have increased the pompous greybeard pontificating. So, apologies in advance if I come across a little preachy, but here we go.


I just finished two days of conference calls as an ad hoc reviewer for a Department of Defense cancer grant program, and the experience was, as always, eye-opening. Our job was to screen hundreds of preliminary applications to see who would get an invitation to submit a full application. These preliminary applications were short: two pages of science, two pages of biosketch, and a page of statements regarding the relevance to the military population. Shorter than a full application, sure, but there were so many of them…my pile alone consisted of 85 applications. It is often said that being involved with the grant review process is important for young faculty to understand how the process works, and I couldn’t agree more. Even experienced scientists fell into holes–they received bad scores for reasons that seemed avoidable. Based on actual fails, here are my take-aways:

Take the career development plan seriously. This kills me a little inside, because this is grantsmanship pure and simple. There is a nugget of honest concern for the trainee and how they are being mentored and supported, and this needs to come across in the application. We screened a number of career development awards, and many grants were dinged because the Career Development Plan section was not sufficiently detailed or seriously considered. It doesn’t fly to spend a paragraph saying basically that your “career development” consists of working in the lab. A list of faculty for a mentorship committee and a schedule for meeting with them. A list of didactic courses that you will take. Defined journal clubs and lab meeting times. These are the elements of a serious career development plan.

Several applicants listed mentors at another institution. While this is not formally a problem, several reviewers, including myself brought this up as a concern. Sure with technology, mentorship can occur long distance, and if this is the case, spell this out in detail. Otherwise, identify a mentor at your own institution.

Educate yourself on clinical needs. There were two grants I crushed because while the cell biology was strong, it was clear that the PI had serious lack of understanding of the disease that they claimed their research was poised to benefit. As an MD that does basic science research, I’ve taken pains to establish my basic lab bona fides, and I’m sorry, but it was too painful to read interpretations of current clinical care that were frankly mistaken. Please please please discuss your grant with someone that is familiar with the disease you are addressing.
Two sections asked applicants to explain how their research would benefit military personnel and/or their families. Many grants were received devastating scores simply because applicants failed to address military benefit specifically.

Clarity is king. Don’t make your reviewers work to understand you. Not only do your reviewers have to read and understand your grant, they have to turn around and explain it to the larger group. Help them. Clarity is an art, sure, so if you are unsure, have other PIs read your grant. You don’t have to “keep it simple,” in fact, I would argue against 100% simple…in my opinion, a great grants, or any science presentation, starts simple, and end simple, but reveals complexity (reality) in the middle.

Keep applying.  Let me say what others might be reluctant to:  the process is fallible and there is no question that some applications get dinged by “bad luck.” We like to pretend that grants are reviewed objectively and that the scores represent some kind of God’s-eye evaluation of its merits, but who gets assigned to read your application, how rushed they were in reading it, and whether the grant is discussed early or late in the day all make an impact. There is a reviewer spectrum sweet spot–too little knowledge of the topic area and the reviewer can’t really appreciate it, or advocate for it to the panel. To close a working knowledge of the area, and small problems can become a topic of extended discussion, something that nearly always drags down scores.

The cold truth is that reviewers are looking for any excuse to destroy your grant. Some may seize on the randomness in the system to call the entire grant process a crap-shoot, but it’s not true. Yes, the competition is fierce. Reviewers want to like your grant, but you have to help them. You will be punished if you don’t take each and every section of the proposal seriously. Your application has to be flawless.

Next time: hints on how to write a flawless proposal.

Facebook Research is like Tuskegee Experiment? Not.

Let’s try this again..

I agree with Dr. Isis that comparing the Facebook research study with the Tuskegee experiment is bananas.  I understand people being upset by the lack of informed consent, but an IRB in this case would consider the degree of potential harm that could be done, e.g. dying of tuberculosis versus reading a sad text on your timeline.  That is what would be considered “minimal risk,” and in some cases informed consent is not considered absolutely necessary.  Facebook manipulates us all the time so I’m not sure this has done any more harm that the usual soul destroying that goes on.  Certainly human subjects issues are worth discussing..

Reflections on loving small science in the cold room

Sorry for the delay, dear readers.  Lately, I’ve been feeling like Howard the Duck.  “Trapped in a world he never made!”  A brief chat with a colleague stirred up my ambivalent feelings about Big Science:  awe mixed with skepticism, and spurred this made me contemplative about my own start in lab…


Saw a colleague yesterday headed off to an NIH study section convened on some kind of crazy idea to sequence single neurons from all parts of the brain.  After a briefly swinging my…knowledge base…a little bit, shook my head at the idea, “Wow, you neuro guys are crazy ambitious!”  It made me think about the contrast between modern biomedical research, and the kind of science I fell in love with.

I’ve loved learning about science for as long as I can remember, but it first dawned on me that I liked life in the lab while a college student labeling Eppendorf tubes in a cold room on 168th street. Years earlier, my 6th grade teacher Mr. Petro-Roy let me take home some beat up astronomy books he was using as bases for a ball game. I’ll never forget what he said when he saw I was assigned to his class, “how did I get blessed with you?!”  Important encouragement for a poor kid with no confidence.  In 8th grade, my science teacher, Mr. Vreeland, would have the class packed up and ready to go out the door a few minutes before the bell every day, and somehow it became our ritual that I would try and stump him with a question.  I loved that.  He seemed to too.  About 10 years ago, I heard that Mr. Vreeland had died.  I get misty thinking about him.

As a college student, I sneered a little bit at professors that admitted they got poor grades in the subjects they were lecturing on.  With irony, I confess now I am one of those teachers.  When I got to college, I had gotten in to Wesleyan University by the skin of my teeth and was a January Freshman (my roommate, with a wicked grin, for years introduced me as such).   I took Genetics along with as many other classes as I could handle and was so stoked to be finally out of a mind-numbing job and a tense home situation.  I took too many courses, and tried to cut corners by taking the Genetics lecture without the drosophila lab portion, which was listed in the syllabus as optional.  The midterm was incomprehensible, and I confronted my professor during office hours.  He told me most of the questions I struggled with were taken directly from work done in the lab, and he was astonished that anyone in class was not also taking the lab.  I got a “C” and was devastated.  Around the same time, I went to the Science Library and tried to read journals with the word “genetics” in their title.  The technical jargon was impossible to understand and in no way resembled the science I thought I loved.  So I concluded after my first semester that I was not cut out for genetics and needed a new plan.

My best friend told me he always imagined I’d be a doctor, so I figured I’d try that.  I made spending money for college doing temporary clerical work and on fateful week I spent at the Muscular Dystrophy Association helping to unpack and sort grant applications.  The head of the office on a tour of the stacks of grants asked me what I wanted to do when I grew up…”Be a doctor, I think.”  Well, to get into medical school these days, you need some research background.  He picked up the phone and arranged an interview with William Johnson a doctor doing research in Tay Sachs disease.  His goofy energy was infectious…”what’s on the docket for today?” he would ask every morning.

In his small lab, I labeled tubes, I ran gels I barely understood.  The time flew by and for a change, I felt that I was playing a small part of a worthy, scrappy effort.  Once in medical school I realized that this is what I wanted to do with my life.

Grand projects are wonderful.  They are stimulus for the economy and they energize the public for the ambitions of science.  In my neck of the woods, The Human Genome Project has unquestionably been a boon to life science and biomedical research.  But it’s critically important that Big Science is funded over and beyond a stable budget for regular science.  If Big Science like BRAINI is going to be funded by stealing money from within the current NIH and NSF budgets, then I am violently opposed.

Younger scientists need protection from the ambitions of their elders.

The practical application of science to cure diseases for example is wonderful, but a cure for any disease would generate millions if not billions of dollars in profits in our current medical care system. IMHO if the research is “translational,” maybe it should be supported by staggering profits of the pharmaceutical industry.

Anyone interested in science, in working to fight a disease, to help other people and join a team of scrappy geeks, let’s pay it forward.  Certainly, I wouldn’t be where I am now without little selfless acts.


Stupid atheist tricks at MIT

I was going to keep my mouth shut on the atheism thing, but an essay the other day in the NYTimes, by MIT’s Alan Lightman (Our Lonely Home in Nature) both amused and pissed me off a little.

I’m supposed to side with the scientists when they go all anti-religion, but this dude went one step beyond and dismissed my own world view in a dangerous way.  Thankfully, he did it in a way that made me laugh.


I applaud Lightman’s humanistic message that we humans need to look after each other.  I could not agree more with atheists like him and Richard Dawkins that don’t believe we should depend on being rescued from our follies by a magic God.   It’s been a few years since Sam Harris’ the End of Faith announced, “F- you and your stupid god.”  OK, I’m paraphrasing a bit there, the book was a vigorous atheist response to the religious fanaticism of the 9/11 World Trade Center attacks.  It’s an important book, great for discussion, but these atheist diatribes rub me the wrong way for two reasons.  Their apparent lack of irony in holding righteous and fundamentalist world views, and their lack of compassion for people who find comfort in religion.  The hypocrisy of a rational humanism without compassion for most of humanity seems to me a shaky foundation.

My view on how people use religion is informed by my experiences with patients on our transplant and leukemia service.  WhenI’m on the wards, the phrase, “there are no atheists in fox holes,” often comes to my mind.  I see good people, regular Joes and Janes, who have been kidnapped by disease and thrown into a world of illness and death they are completely unprepared for.  Good for Christopher Hitchens who can face death with areligious rationality.  Good for Richard Dawkins who can contemplate the horrors of the known and the abyss of the unknown with a calculus textbook and the complete works of Shakespeare for comfort and guidance.  But, for the um… “handful” of people that weren’t educated at Oxford or MIT, a concept of God is a fucking useful tool for understanding and communicating about the universe.  It pisses me off when the intellectual 1% look down their noses at the struggles of their fellow men and women trying to make sense of their world.

I smiled when, in the first pages of Dawkin’s “The God Delusion,” he says he isn’t arguing against the God of Einstein and Spinoza because theirs is an esoteric view held by an insignificant minority.  Ha!!  That minority is me!!  And the nature-based religion I hold dear is the view that Lightman takes a swipe at in his piece.  Briefly, the foundation of Spinoza’s view is that there is no separation between the creator and the created.  This division is the foundation of the Abrahamic religions, but serves a mostly political purpose, and erasing this line brings the religious and secular worlds into harmony.  Spinoza believed that studying the world was the way to get closer to God.  “Nature is God,” is an oversimplification, but comes close.  Which brings me to what was humorous and mildly offensive about the “Our Lonely Home in Nature” essay.

The first thing that made me smirk was the arrogance in the guise of humility.  The Lightman piece describes his near-death experience in the Aegean Sea.  He and his wife lost sight of land and the experience of nearly getting caught in a strong wind changed his life.  He realized that, “there was no compassionate overseer or oceanic consciousness…”  Sure, many of us have had the realization that, hey, I could die here.  I have sympathy there.  Life is fragile, for sure.  What made me chuckle was the light bulb over this guy’s head, thinking, if the universe doesn’t care about me personally…then the universe doesn’t care about anyone.  Heh.  If I’m not the center of the universe, then the universe is an ass!!  That made me laugh.

The smile was wiped off my face by Lightman’s core argument that, “Nature, in fact, is mindless.”  Ok, hold up, that view is deeply stupid.  My childhood was infused with science fiction and I’m still fascinated by the question of whether there is intelligent life in the universe besides ours.  Think about non-human consciousness for a minute.  If there are other life forms out there…you think they will look like Tasha Yar*?  Doubtful.  One could argue that the greatest challenge in our search for extraterrestrial life is our lack of imagination regarding what constitutes life and intelligence.  Beyond star-gazing, the “nature is not intelligent,” view is dangerous for life here on earth.  Lightman advocates looking with our own limited intelligence and profound ignorance at the infinite complexity of Nature and concluding that there is no mind there because we don’t recognize ourselves in it.  Do I recognize myself in my fellow humans?  Sometimes.  Not always.  If someone is different from me, if someone doesn’t care about me, does that make them mindless?  No.  Lightman has taken secularism to an extreme that undermines not only Western religion, but also core principles of Eastern religions (e.g. there is no real separation between you and the universe) and condones a close-minded outlook that shuts out our fellow humans if they don’t look like us.


* Thanks to DrugMonkey for pointing out that Tasha Yar was, in fact, human.  I agree, Kira Nerys would be better example here..

How we fix the NIH

 I was on the beach in Florida with a business school prof friend of mine a couple of weeks ago and he blew my mind.  I like big ideas about how to change things for the better.

He’s always up to something interesting.  When I asked him, “what are you working on?”  he surprised me.  “Fixing the NIH grant system,” he told me.  What!?!  He gets paid as a consultant to jump in to an area he may not be familiar with, do some research, and then be the answer man.  Someone from the NIH was in a executive managment course he teaches and described the grant “problem.”  I love this guy because he approaches complex problems like such a boy scout, with an earnest optimism that any situation can be improved. Whether it be how to get our 6th grade basketball team to play better offense, or how to fix the national debt, he’ll say, “here’s what you do..” and roll out a Four Point Plan.  It’s funny…at the same time, I can’t help but play the devil’s advocate and bring up all the complexities and possible roadblocks.  But this is an important topic, so let me step out of the way and tell you what he said …

His primary recommendation was to crowd-source solutions to revamping grant review.  This is his entry for what he proposes to be an open competition for proposals on how to fix the grant review process.  His basic idea is simple, but would be revolutionary.  He proposes that projects should be categorized and evaluated in four separate research categories, based on how the work relates to existing paradigms, and that NIH funds should be evenly split amongst these bins.  This concept of research diversification is taken from the business world, and it’s designed to speed progress and limit risk by spreading support for knowledge generation across classes of research. A key element of this plan is that competition for funds be within these groups so we fund the best of each type. Based on research he did with NIH scientists, the categories he proposes, are:

1.  Pre-hypothesis or exploratory studies.  These are experiments and projects that may not claim to have a paradigm or hypothesis but are designed to gather new information.  

2.  Replication studies.  We had a discussion about this one because I don’t think anyone in science really sets out to do work replicating the work of someone else.  My friend told me that respondents to his questionnaires told him otherwise.  In any event, in a way, this is the most intriguing category to me because it addresses the crisis of reproducibility in science while at the same time giving validity to scientists who are technically adept and hard working but who may not want to compete in other areas.  no one I know in science would admit that that We had a discussion about this

3. Paradigm extending studies. This is where most NIH-funded work currently fits.  Many bemoan this “safe” way of funding research, and one great strength of this system is to limit the amount of resources that go into “incremental” work.

4. Research that may develop a new paradigm.  This is the type of work that gets the most press and that everyone vocally supports.  Fresh thinking, new ideas, etc.  It’s an intriguing and common-sense ideal to compartmentalize this type of work, to recognise that paradigm breaking is high risk and that not all resources should be put in this basket.


A final important point of this scheme is that if it is adopted across institutes (?!) it would facilitate consolidation of bureaucracy.  By imposing a constant framework like this one, it would allow cross-institute comparisons.  And lastly, he proposes to grade the success of grantees with a new objective measure of knowledge generation.  The belief being that papers and patents are not a sufficient index of how well the money was spent.  How should we measure how much useful knowledge is generated by a grant?  That’s the big question, and he says let’s open that up to crowd-sourcing.

What do I think?   I have mixed feelings about shaking up the grant system just at the point when I think I’ve learned the game.  But, it’s clear grantsmanship is a game, and that we owe it to eveyone involved to make it more transparently about funding the best research.  The more I thought about this system, the more I can see its benefits.  The primary road blocks I see to implementing this system are lack of political will, and getting study sections organized to deal with this restructuring.  Study section culture is rigid and I’m not sure whether study sections would subclassify the grants they get or whether new study sections would be needed.  I’m really curious about what my colleagues think of this scheme.


Is science a polytheistic religion?

“The experimental method is concerned only with the search for objective truths, not with any search for subjective truths…An anticipative idea or an hypothesis is, then, the necessary starting point for all experimental reasoning.  Without it, we could not make any investigation at all nor learn anything; we could only pile up sterile observation.”

    –Claude Bernard, An Introduction to the Study of Experimental Medicine


Claude Bernard: “Oui, I’m dead…but do I look naive to you?”

The other day, I told Dr. Isis I wanted to do a PubStyleScience on epistemology, and she said, “I don’t get it… what’s so hilarious about that?” Or words to that effect. Imagine my shock and surprise!  A bunch of scientists, sitting around, drinking and arguing about the meaning of everything?  It’s the *perfect* topic for PSS!!  So, let me explain my interest in the topic…

I like to share science and the culture of science with anyone who’s interested, especially to show a relaxed side of science to younger people who may be put off by narrow-minded cultural attitudes. PubStyleScience is a science culture experiment along these lines.  Let’s open the doors and windows of the scientific enterprise!  I see many sci’s on Twitter motivated to expose and correct sexism and racism in the scientific enterprise, to promote fairness and transparency.  We can agree that there is some bullshit cultural baggage with science community, but I’m more interested in the subtle baggage that keeps us from doing the best science.  I am often surprised at how scientists embrace groupthink.  In the abstract, the NIH (for one) declares a love for radical departures and fresh interdisciplinary ideas.  And yet, as a scientists love to run in a herd, and in evaluating others, demand conformity.  Professional science should be open to a diversity of participants.  This is a moral principle, and a conviction that the progress of science will benefit from the participation of a wider range of voices.

So what I’m interested in is the *positive* side of scientific cultural evolution.  My tweeps rail against what they don’t like about the old culture…but what are we *for?*  For most of the scientists I interact with, we can easily agree on the extreme ends of “unacceptable,” e.g.sexim and racism.  But there are softer cultural values that are not clear-cut, but messy.  How should we define the differences between “good culture” and bad?  An example of the changing mores of science is the idea of “Kerning,” a word which was coined several years ago after an earnest but tone-deaf opinion piece by cancer biologist Scott Kern.  

In it, Kern lamented the erosion of a lab culture that valued working through the weekends.  His “where’s the passion?” lamentation was lambasted by Drugmonkey and Dr. Isis.  While I agree with some criticisms of Dr. Kern’s piece, e.g. science should not be closed to people with families that need to work 9-to-5, I sincerely believe that intense, clock-ignoring passion is a critical ingredient for good science.  Can we revisit the passion and hard work debate?

As the culture of science evolves, I want to understand and communicate to the next generation two pillars:  a new, open and diverse culture of science, as well as the essentials of the scientific method.  And here’s the question that I would like to discuss:  are these two pillars utterly distinct, or does diversity in science require being open to different views of the scientific method?  This is where the philosophy comes in:.  How do we separate conjecture from reality?  How can we know what is true?   Science is not set of sciencey facts or topics, it’s a philosophy, a way of thinking, an approach to understanding the universe.  I worship the scientific method, I admit.  But if science is inherently human process, Is Claude Bernard search for objective truths naive?  If the process of science is inherently human activity, one that may not lay claim to objective truth, I start to wonder:  is there a clean line between the method and the culture?

Then, my mind was blown when I stumbled on to the existence of a Feminist Theory of Science.  Being the interweb, I should have known this has been discussed before.  But it’s a radically new idea to me.  And the next obvious question:  if there is a feminist science, is there an Irish theory of science and a jewish theory of science and a South American theory of science?  Does everyone get their own science?  Hmm…not sure, but I don’t think so.  I think there should be a core set of values.  Where do we draw the lines?  This is a question of epistemology.

Is there any real-world relevance to this philosophizing?  I just got back from a new investigator meeting at the National Cancer Institute (NCI) where we were deluged with data and information about the byzantine workings of the NIH.  The NIH recognizes that URMs (under-represented minorities) are under-represented among NIH grant awardees, and that this problem is getting worse given the changing demographics of the USA.  The NCI is working to try and fix this problem , but as I was being intensely immersed in the bizarre culture of US science funding at the NIH, I couldn’t help but wonder if our narrow view of “proper” science culture is part of the problem.   The NIH also seems to have mixed feelings about “big science.”  Big versus small science deserves it’s own post, but briefly, the NIH pays lip service to the importance of individual investigator grants, and yet, they sacrifice many R01s for big science projects.  Let’s have a whiskey and discuss.


Neil deGrasse Tyson, astrophysicist and science communication superstar

 “This ad­ven­ture is made possible by generations of searchers strictly adhering to a simple set of rules. Test ideas by experiment and observation; build on those ideas that pass the test, reject the ones that fail; follow the evidence wherever it leads and question everything. Accept these terms and the cosmos is yours.” –Neil deGrasse Tyson, on Cosmos

Unsolicited advice for a triaged grant

A scientist on Twitter lamented the other day that she had her A0 grant triaged. As an expert in triaged and unfunded grants who eventually overcame to get funded R01s, here’s some unauthorized, off-the-cuff advice.

What happened to this scientist’s grant that caused it to be triaged? Of course I don’t know for sure, but I’m willing to bet one reviewer read the grant carefully and saw strengths as well as weaknesses, but the other reviewer was dismissive with a cursory read. The problem is, without uniform enthusiasm, triage happens. Due to flat/declining funding over the past dozen years, competition is more intense today than ever before and study sections are encouraged to triage grants mercilessly.

I may seem vague, but that’s intentional. With a triaged grant, the problem is not likely to be with the details of the methodology but rather with the overall excitement for the proposal. When she wrote the grant she probably thought very carefully about the experimental design and feasibility of experiments. What was missing was zazz.  That’s right.  The missing ingredient was essentially jazz hands.

From 30,000 feet, the Specific Aims page, you want your reviewers to be thinking, “Wow!! Can she do that??” The rest of the grant is focused on making the case that, “you bet your ass I can.”

I’ve had discussions about whether a triaged grant can be salvaged for resubmission. While there’s always stories of grants going from triage to funded, this is the exception. Experienced hands put a triaged grant on the shelf for year, and try something completely different. Preliminary data, may be recycled, but a new approach, a new set of Aims are needed. This is debatable of course but what’s not debatable is that there was a serious enthusiasm gap and the grant needs to be rethought.

My tweep commented that “I really liked this grant!” Let me be provocative and say that this was part of the problem. If you “like” your grant, who is going to love it? you don’t need to like your grant, you should be psychotically passionate about it. You should have scary eyes for your aims, and bring unreasonable amounts of firepower to bear. I like to watch the lobby scene of the Matrix to get the idea.  In The Matrix analogy, the experimental tools of your experimental design are the guns.  Note how Neo and Trinity treat their weapons,  dropping them when they are spent and moving on without hesitation.  Do Neo and Trinity “like” their guns?  Tools are used simply to achieve the goal.

Another problem with a scientist “liking” her grant is that it sets her up for feeling discouraged by its rejection. Nut up. This is business. Don’t get discouraged, get angry. Take a couple of personal days for reflection, but then pick yourself up, dust yourself off and get back into the fray. Keep writing.

Change of gears.  The PubScience in me wants to say,  “Hey, young ‘uns, let’s cut the B.S., you’re listening to advice from old man telling you how to act like him.  An alternative explanation for a rejected grant, is that the NIH only likes to fund old people.

I’m being facetious, but only a little.  Who still thinks it’s a good idea to have the fate of  creative and groundbreaking ideas decided upon by a committee monoculture? I agree completely that the NIH grant process needs to be rebooted, as @MBEisen and @Drugmonkeyblog have discussed (and I refer you to them for a more systematic and objective (?) discussion).

Briefly, and irreverently, my view on what’s wrong with the NIH process is that the smarter people try to be, the more danger there is in them being dumb asses.  This view of course was influenced by my own sordid grant history.  My currently R01 funded project is not what I started out with — I had two projects that failed agonizingly to obtain successful R01 funding, after 3 rounds of grant reviews each.  First one, then the other broke my heart as the A2 scores came back nearly the same as the A1 score, unfundable, after massive efforts to respond to A1 reviews.  (@drugmonkeyblog recently wrote about this phenomenon)  It’s deeply ironic to me that the “deal-breaker” criticism of each grant was neutered by the passage of time.   My first R01 application included an Aim on making and using a mouse knock-in model of the disease I was studying.  The final judgement was that without the engineered embryonic stem cells in hand, there was no way the grant should be funded.  It was rational decision on the part of the reviewers.  I was depressed, but their judgement seemed fair.  And yet, a similar knock-in model was later successfully created by another lab, and the insights it has yielded have yet to live up to our hopes.  To my mind, the “alternate approaches” I outlined in my grant may have been the better approach.

The case of my second project makes me smile even more ruefully.  Although I now had a disease model in hand, my experiments were considered  unworthy because my model did not, in my reviewers’ opinion, adequately recapitulate human disease.  The primary reason I pursued my Myc-driven model of acute myeloid leukemia (AML) was that it looked, to my hematology-trained eyes, exactly like human AML.  But, the scientist experts on study section noted, my mice had AML that was oligoclonal (comprised of not a single malignant clone, but several), and this was clearly not the case for the human disease.  Case closed.  Sigh.  Except… now, a few years later, we know that human AML is, in fact, oligoclonal.  Oops.

People often inquire about the experiments I proposed in that grant, but we had to drop working on it.  My bottom line is that while the writer of an unscored R01 needs to do some serious re-working, the NIH also has some serious re-working to do to address the reality that the job of a scientist has become predominantly about playing the grant game, which takes years of experience for most of us, rather than rewarding the smartest creative minds, which are usually younger than the grey-beards we reward now.