Everything does NOT happen for a reason

(by potnia theron) Aug 15 2017

I do not believe that everything happens for a reason. At best, that is post-hoc rationalization and type I error. At worst, it is magical thinking to protect one's self from reality.

The world, for the most part, presents itself to us as a large random number / event generator. Other people, other actors, other agents, have reasons and rationales and justifications for their acts. And we do not, cannot, control them. And frequently when we try to control them, it backfires. Often spectacularly and horribly.

Whether we control our actions and feelings is quite open to debate. That's another rabbit hole that people of religion are quite willing to go down.

Why is this worth pondering? Because, one can't control that random universe, but one can position oneself to take advantage of it. One can be in a place where more and good random things are more likely to come your way.

Take for example staying in place vs. leaving the region/city/whatever you grew up in. I call this the Patty Duke effect (ah, certain people of a certain age will remember Patty and Cathy and the rest of you, just don't worry about it). There is a comfort and support for being in a community, and being in the same  community. My partner is Patty, who, with the exception of 3 years has lived in a 10 mile radius of the parental house. When we go out to dinner, we are inevitably approached by people saying hi. My partner is deeply imbedded in this community and it is a joyful thing.

I am more of a Cathy and while I haven't lived most everywhere, I've done a lot of moving for all sorts of reasons, including better jobs, other partners, parental units. I think its helped me grow, and become much more than I would have been had I stayed in place.  There are inevitably more opportunities to do different things with one's life, if one is willing to move and seek them out. It's increasing your sample size, and being less likely to make a type II error in life.

Yesterday, I had a marvelous young person in my office talking about her future. Or her perception that she is "stuck" and doesn't know what to do with her life. Grad school? Follow a partner? Work and earn some real money? She had a friend, she said, who is a school teacher, married, and just bought a house. All at the tender (to me) age of 23. It made her feel unaccomplished, and well, stuck. I tried to give a different perspective. "You're not stuck" I said. "You are free and flexible". I wish I had said "you are a bird on a branch and getting ready to fly."

It was relatively easier for me at 22, to be a Cathy and move. My parents had. While they put down roots to raise a family, and found community in middle age, they are also helped push me and my sibs to go see the world. I am grateful for that. My partner's children are Cathys too, which I admire in my partner, for pushing these kids to go out into the world. One child is queer, and would have been bitterly closeted and unhappy in the small local Patty-community. I love my partner's kids, and while they can be infuriating (they are in their 20s), that's part of the charm, and part of their strength, and part of why I love them so very much.

So, to the incredible young person, debating life: You are a minnow and the ocean is wide, and this is a good thing and a scary thing. Enjoy, revel in the fact that you do have a choice. That hasn't always been true for young women in our society, and there are still many places where it is not. Swim and Fly and grab life with both hands.



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quote of the day: dreams edition

(by potnia theron) Aug 15 2017

This is the thing of which I am most scared.

“There are people who put their dreams in a little box and say, 'Yes, I've got dreams, of course I've got dreams.' Then they put the box away and bring it out once in awhile to look in it, and yep, they're still there. These are great dreams, but they never even get out of the box. It takes an uncommon amount of guts to put your dreams on the line, to hold them up and say, 'How good or how bad am I?' That's where courage comes in.” ― Erma Bombeck

I'd like to say this is only since I've become an olde farte, but that's not true.

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Change in NIH human subjects policy

(by potnia theron) Aug 14 2017

From Mike Lauer. Comments & thoughts later:


Message to NIH grant applicants/awardees, contractors, researchers and research administrators:

If you are conducting NIH-funded research that involves human subjects, or are considering applying to NIH for support of such research, we want to call your attention to important changes that may affect how you:

  • select the right NIH funding opportunity announcement
  • write the research strategy and human subjects sections of your application
  • comply with appropriate policies and regulations

First, familiarize yourself with the new PHS Human Subject and Clinical Trial Information form. For application due dates of January 25, 2018, and beyond, you will be required to use an updated application forms package (FORMS-E), which includes the new human subject and clinical trial form. This form requests human subject and clinical trials information at the study level using discrete form fields, which is a change from current practice. Contract proposals will also require this information. Learn about the new form here.

Second, take a moment to answer these four questions about your current or proposed research:

1) Does the study involve human participants?

2) Are the participants prospectively assigned to an intervention?

3) Is the study designed to evaluate the effect of the intervention on the participants?

4) Is the effect that will be evaluated a health-related biomedical or behavioral outcome?

If the answer to all four questions is yes, then your proposed research meets the NIH definition of a clinical trial. Clarified and broadened in 2014, the definition encompasses a wide range of trial types: mechanistic, exploratory/developmental, pilot/feasibility, behavioral, and more. NIH expanded the clinical trial definition in response to widespread calls from diverse stakeholders for improved reporting of research milestones and outcomes, and for assuring maximal transparency.

Need help determining whether your study would be considered by NIH to be a clinical trial? See our webpage on the definition that includes case studies, FAQs and other resources that can help. Still unsure?  Contact your NIH program official or the scientific point of contact listed on the funding opportunity announcement to which you are applying.

Third, familiarize yourself with NIH policy changes related to enhancing stewardship of clinical trials.

NIH made a number of policy changes to improve the stewardship of clinical trials across the life cycle of the trial. We encourage you to familiarize yourself with all that is changing, including:

  • the requirement to apply to an FOA that specifically allows for the submission of clinical trial applications for due dates beginning January 25, 2018.
  • Good Clinical Practice training expectations for NIH staff, grantees, and contractors that went into effect January 2017.
  • updated peer review criteria that will be included in FOAs for clinical trial applications and solicitations for due dates on/after January 25, 2018.
  • new Human Subject Information form requirements for clinical trials that will be included in updated application forms (FORMS-E) for due dates on/after January 25, 2018, and contract solicitations published as of January 25, 2018.
  • use of a single IRB for non-exempt, multi-site clinical trials for application due dates on/after January 25, 2018.
  • expanded ClinicalTrials.gov registration and reporting to include all NIH supported clinical trials.

Improving the design, efficiency, and transparency of clinical trials is important because it:

  • respects our ethical obligation to participants to maximize the use of the knowledge from the trials in which they participate
  • facilitates design of clinical trials while reducing unnecessary duplication
  • promotes broad, timely, and responsible dissemination of research information and results
  • fosters responsible stewardship of the public’s investment in biomedical research


We have developed a new Clinical Trial Requirements for NIH Grantees and Contractors web page to bring together all the information you need to know.  Please review this information carefully.  Your attention to detail will be critical to ensuring successful funding of your clinical trial awards.

We will be putting out a series of reminder policy notices, training opportunities, and other resources in the NIH Guide to Grants and Contracts, in the NIH Extramural Nexus, and on my blog.

The success of clinical trials relies on the public trust in scientific rigor and ethical oversight.  We all play a critical role in this process.  We are most grateful to you for your help and support.




Michael S. Lauer, MD

Deputy Director for Extramural Research, NIH

One Center Drive, Building 1, Room 144

Bethesda, MD 20892


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Finding Joy in Life

(by potnia theron) Aug 14 2017

I am sitting here in my apartment, with morning sun falling in through the large east windows. I am joyful, and remembering just how damn good it is to be alive. Yes, there are problems in my life right now, though, no, I don't feel like sharing them here. One reason is that they seem so distant in the sun. I feel like I can do anything.

I saw the movie Moana, and finally, a disney princess in which I can believe. It's important to have hero/role models that look like one, but its also important to see heroes in people who do not look like one This latter is true for me, as I am not Polynesian/Maori/Hawaiian. No, the movie is not deep, and it wears its message on its sleeve. But I cried during the scenes where she stamps her foot and says her name.

I have known terrible depressions, externally generated or internally opaque to me. But I have always managed to find my way back to joy and the beauty of the world. I know there are others who do not, cannot, will not.

Then there are the friends and colleagues who rejoice in dwelling in dark places. Some of these folks fancy themselves witty and erudite for seeing the world through grey or brown or dull blue glasses. Some of these wear not just skepticism, but negativity like a cloak to protect themselves from something they fear, but cannot name. There are reasons: problems in the past, abuse, emotional neglect, the list is as long as the Canon. Some of these friends, people I know well, and love, and embrace, can no more change this outlook then I can stop being inappropriately goofy with the happiness inside of me.

But one of the things that makes me sad is the inability to shed that drab blue and faded brown outlook. I've had students and techs and collaborators who are cynical and ironic and see disaster at every turn. Hell, I've had partners I lived with like that. They are people who cannot look at a piece of work, something they did, and see the beauty in it. "Here's another stupid thing I finished".

There are many kinds of lack of support and encouragement. You can be critical and a perfectionist and see people as failing to meet your standards. But there is the one where it all seems pointless. This isn't mentor failing to support mentee. This is friend not seeing the beauty in friend. This is reading a paper and nit-picking your way through it, and not being able to say to the first author: Wow, I took a step back and you've done something really, really good here.

I was talking to my summer medical students who have another week or so in my lab. This year's batch was one of the best ever, if not the best ever. When they interviewed with me, and then again when they started I promised them that they would work harder than any of their peers in the same program. That the hours, because of the experiments, would be longer, and that they would be more challenged. I said this is because they would be partners in the work, and the work is hard. Yesterday, I asked them if they though it was true, and they all said yes, but, ... but.... what they got out of it was worth it. We talked about how to write the first draft of their letter of recommendation (from me, for their future projects). And they started listing what they learned: surgery, electrophysiology, and then they went beyond techniques and talked about working together and compassion for the animals and their co-workers. Their faces held joy.

Life is short. Being happy is better than being miserable. Making the world happy and better for someone else is one of the greatest accomplishments we can have. We can choose. I do not believe I can make those ironic and unhappy friends better. I can't. You can't. But I can set the space, create the place where it CAN happen.

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Two perspectives on "dis"-ability

(by potnia theron) Aug 11 2017

WaPo just had two op-eds with  interesting perspectives by people that if one is not a clinician taking care of people with achrondoplasia or stroke survivors, one would not meet or work with every day. One is by Rebecca Cokley, a former exec director of National Council on Disability, who has achrondoplasia,  a disease that reduces bone growth, and as she says "the most common form of dwarfism".  The other is by Robert Fowler who had an ischemic stroke (blood clot in the brain). These two are different perspectives, and dealing with different issues. What united them in my mind was yet another reminder to me about the world out there. We, I, get so wrapped up in life that I can easily lose track of other people and their stories. People with physical challenges, people with "dis-abilities" often more so than people who just look different, are easily swept under the rug, and locked in a mental closet out of site.

Surviving a stroke is difficult, and Mr. Fowler is wrestling not only with  different physical capabilities, but with the shame of asking for help. He didn't intend to be ill or poor but has been dealt a rather bum hand. Not his fault that his parents weren't rich and that he can't afford the best health care that private insurance can buy.

There are good reasons, defensible reasons to promote a culture of "a hand up not a handout", and we are all or should be Clint Eastwood and Chuck Norris and totally self-reliant. Except, of course when we are not. And then it's hard. We are supposed to battle cancer, and be warriors in our own life. The metaphors of illness are of war and battle and fight. When I was very ill, I was just too damn tired of being sick to explore metaphor. And the asking for emotional and psychological help carries a stigma that makes the physical burden even more. Mr. Fowler paints this picture clearly.

Ms. Cokley has had achrondoplasia since birth, and is the third generation in her family. Her concerns are based on the announced breakthrough in gene editing and represent a much more difficult ethical dilemma. She makes the strong point that this announcement came on the anniversary of the ADA (Americans w/ Disabilities Act), a landmark piece of legislation that our current president has yet to understand. Ms. Cokley rightly points out that the language in many of the press releases talks about "unfit" and editing out mutations as "progress" and "remediation".  Her language is beautiful in describing the pain that "adult little people" felt when the gene was discovered:

I remember clearly when John Wasmuth discovered fibroblast growth factor receptor 3 in 1994. He was searching for the Down syndrome gene and found us. I remember my mother’s horrified reaction when she heard the news. And I remember watching other adult little people react in fear while average-height parents cheered it as “progress.”

How, if you are an average-height parent, do you explain to children whom you’ve spent years telling are beautiful the way they are, that if you could change them — fix them in a minute — you would?

Her discussion of the community and culture of little people is similar to what my Deaf friends, and my friends who sign, talk about for their life and community. They do not want cochlear implants at birth, they do not want their culture and their society, rich and complex, taken away. I freely admit to struggling with this. Music is so central to my life, how could I trade anything for that? But I try and listen, and Ms. Cokley's story is a good listen.

Her argument against gene-editing has two parts. Firstly, again, she talks about the beauty and the potential and the culture of being different. What is lost if every "imperfection" is corrected? What is lost if we all became perfect. This may seem to us, able-bodied as a reducto ad absurdum. How can we fix everything? But it is not for people within that culture.  Her other point is the ugliness of, as she says "society’s fear of the deviant — that boogeyman of imperfection'. It is what people, maybe too old for gene-editing, hear when normal-height (and that word sticks as I type it) say "fixing". In some ways physical differences, that are not skin color, or body size, are things we apply "dis" and "non" and "anomaly" and other words that mean "less" and "ugly".

Ms. Cokley implies that she wants to pass this culture, her culture,  on to her children, and does not want "fixes". She talks about how the vague language of the scientists and clinicians who talk about fixing "serious disease" avoids pinpointing what needs to be, or ought to be, or should be, fixed, once the "can be fixed" is done. There are discussions that have no occurred, part of her point. The articles about gene-editing do not talk to the people who might or might not be fixed and edited.

What is a parent to do in this situation? A parent who has not grown up in the culture of little people or Deafness might only want the best for their child. And one issue is that some of these "fixes" might likely have to be done at birth, or in utero, well before the human being who bears the gene can make a decision for him/her/xe self. If teenagers can rage about "why didn't you make me practice the piano" as much as "why did you torture me so much to practice piano", how much more rage will there be over the choice to edit or not edit one's genes? Is gene editing like gender fixing surgery of years gone by, when decisions were made about ambiguous genitalia at birth, something we now rightly regard with horror? Or is it like vaccines, where the ultimate good, to the individual is so strong, we want to mandate it (and yes, I recognize there is societal good to vaccines that may not apply here)?

I am grateful for these voices that make me think, once again, about the problems I do not understand.

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Really? Screw that ... (interviews with more brilliant tech break-through types)

(by potnia theron) Aug 10 2017

Ozy, which I try not to read, had a profile of James Park, who heads up FitBit. How does he stay ahead? The tagline from the article is:

In a behind-the-scenes interview from OZY Fest 2017, James Park shares his tips for success: sleeping five hours a night and always preparing for the worst.

When you delve into the article (and I don't necessarily recommend that), it's a bit more complex.

Park: I only get five hours of sleep a night. I  know that’s bad and I need to work at it, but it’s gotten even harder as I’ve gotten older. I just find it difficult to settle my brain at night.

Damn straight its bad.

3 responses so far

Quote of the Day

(by potnia theron) Aug 10 2017

From my bestie:

My best ideas come at the intersection of desperation and exhaustion.

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If not everyone can be a scientist, who gets to choose?

(by potnia theron) Aug 10 2017

People, in PhD programs, in post-docs, leaving science, is an ongoing discussion, here and elsewhere. The causes of leaving engender passion and righteousness, and self-righteousness. There are manifestos, diatribes, and not some small amount of sadness.

Everybody agrees that there are probably not enough (meaning enough for everyone who might want one) jobs (meaning the preferred employment, in these discussions an academic professorship) and support (meaning an NIH R-level grant).

Part of the discussion I've come across is trying to separate out the legitimate selection mechanisms from the ones that are socially imposed. The latter are excoriated for not selecting "the best" of science. I think all right thinking people agree that the "this group is stupid and can't think" arguments are prejudices and entirely without merit. Beyond that, we enter the realm of more subtle concerns. Being subtle means only that the roots and branch implications are not immediately apparent, not that there is defensible value in those concerns. I find I quickly get confused when I read these things.

In other fields, that a sorting and selection process occurs is taken for granted. No one expects that every high school athlete will make it in the pros. Artists, visual, dramatic, performance, are all too aware of the difficulty and challenges of success, and often the mind-numbing finality of the "day job for just a while".

A small aside, but probably quite relevant in the long run: One of things that interests me is that in art, visual or performing art, some of those forces, the bad forces that keep people out, or try to keep people out, or even are just making it very difficult to succeed, are exactly those forces that shape the art and make it compelling, valuable, worthwhile, important. Stories told in a vernacular, stories told in the language of the oppressed, may not have been high literature once upon a time. But the power of those stories, told in those languages, move us, change us, make us more than we would have been. We come to recognize, society comes to recognize, art in a new form, art that grew out of efforts to keep the artist away from creating. We may argue today about this modality or that, but history shows us what we were foolish about 100 years ago. Stravinsky, Gauguin: does anyone doubt their art today?

In some ways, sport as an career choice is more clear: it is competition. Winners tend to be very obvious. Better is judged by winning. And that competition, the mental rigor of that competition is part, perhaps a very large part, of what drives individuals towards success. Art and science are, again, more subtle. If you lose a tennis match to Serena Williams, you know it. When does an artist decide that they cannot live on beans and rice and in an apartment with less desirable urban roommates, human, insect and rodent?

Is science different from art? In the discovered/undiscovered, there are some synapomorphies of human endeavor. But for every Stravinsky who endured and persisted, there was undoubtedly a woman of color, a person with disabilities, a working class individual who never got the opportunity to leave the factory in which they worked, whose music we will never know. There are people who did science against the odds, but also probably lots more who might have changed our lives, people who never had the right combination of resources and luck to be what they could.

So, what is our responsibility, aware that we are of their potential existence, to young people today who might be scientists (let alone artists)? We all decry those dystopian novels where there are tests and trials and some Greater Authority makes the decisions. But we are also not happy with a random river of time and chance throwing greatness up on the banks of society.

Had we but the resources, we would give every child the opportunity to explore and be educated and find what they can and will do. But large swathes of the world don't have enough food and health care, let alone basic education.  The anti-dystopian novel (think "The Giver") where the young rebel escapes the deterministic society and goes off to find what they are and Make A Difference is as unrealistic as the utopian visions. Aside from value as parable, these stories are disturbing. They are often framed as genius, of one sort or another, against the world. It’s often only the protagonist who escapes, and the Rosencrantz and Guildensterns of society, perhaps not genius, but perhaps creative, are left behind. What happens to them?

[Another aside, while there may truly be geniuses, and “top of the game” scientists, it is not a binary, bimodal distribution. It is not. There is not the .1% of incredible science, and the rest is trash, as has been asserted by many people. It is not normative and transformative science. The reality of scientific effort, product, output is far, far more subtle than that. Alas, another post].

If we all truly, really, deeply and meaningfully cared about that lost genius, let alone the good but not quite genius, we'd stop doing what we are, which likely has minimal impact on the lost children of human society. We would become activists and teachers and do something to effect change so that those children would have the chance to realize their potential.

Ah. But we have our rationalizations: I am better at doing my science than I am at organizing. I can do more good teaching here than I could in South America or Africa or rural anywhere without education for female children, non-binary children, children with handicaps and differently colored skin and eyes. If I make money, I can give it others, and that may do more good.

So we persist and do the small things that we can. Changing the world is hard. In my youth, I surely thought everyone who wanted it deserved a kindly mentor and a full stipend and a chance to be a scientist. I am unsure that that statement is false. I am also unsure that it is true. While many things have become clearer to me with age, this is not one of them. How do we choose who gets to be a scientist, an artist, even a doctor or lawyer or candlestick maker? Right now, the world is out there, and people, young people with dreams and wants, go at it, as best they can, with the tools they were given as children. The world while sometimes helpful and sometimes cruel, is largely indifferent to their efforts. Unlike sport, there is no ultimate World Series to determine who gets to be the best. There is no Final Four of college or grad school. We try, and the world throws its stochastic self at us in the form of mentors and opportunities and people we meet and talk with. So we teach them resilience and persistence and help in the ways we can.

9 responses so far

Compliance City Blues: Dealing with the IACUC or IRB or OSHA

(by potnia theron) Aug 07 2017

When I was a wee thing, compliance issues consisted of not blowing up the lab (too often). Or not using extension cords as clotheslines for hanging up wet X-rays to dry ("really, Dr. Theron, it wasn't like it was plugged in or anything"). I can't speak to what IRB's were like, as I wasn't doing any human research in those distant days. But we all have heard of the horrible excesses and unethical goings on of the times. If you haven't read Rebecca Skloot's excellent book The Immortal Life of Henrietta Lacks  you should.

For those of us that work with animals, we all know and love and work with, the Institutional Animal Care and Use Committees that govern our research lives. I lived through the no IACUC through ineffective IACUC through the regulated situation in which we do our work today. I have sat on my University's IACUC in the past, and been the stats person for the IACUC. It was in no sense fun. Even free lunch did not help.

My rule: do not offend the IACUC. Follow the rules. yes they will seem arbitrary. Yes you will be irritated and forced to compromise things that, in your perception, are Best for The Science.

I know plenty of people who bend the rules. But one of the things that I have learned is that by and large IACUC rules are not good ones to be bent.  I know people who live by "tis better to ask for forgiveness than permission". IME, this seldom works with IACUC's and their escalating scales of penalties.  Some Big Dogs I know are beyond rules. The worst, when caught, blame people under them, oblivious to the culture they have created. Some PI's are quite compulsive and follow everything. I had a colleague whose benchtop had outlines in masking tape, with a number, of where every piece of equipment needed to be, and a cross-indexed master list of places and equipment. In the days before personal computers, this was a hand-typed list.

In my lab, IACUC, IRB and compliance are unbendable, rules which cannot be bent. I've got two lines of justification for this: ethical and practical. Practical involves the level of problems that occur when one is caught breaking rules. These problems can grow into a moratorium on doing research with animals, a situation which can be devastating to all of the people in the lab. The decisions on which rules to bend are essentially ethical ones. None of us would do something that we perceived as "hurting the animals". And even if this instance of breaking the rules wouldn't hurt the animal, another instance might. The trouble with rules is that you can't plan for every instance.

I have found that the temptations to bend the rules usually stem from poor planning. Something MUST be done, or the experiments will fail, and the means to do so are not within the protocol (people, drugs, etc). The other category of bending comes from laziness or obliviousness, though it is seldom seen that way: I just don't want to get out of bed to go check on the animals. Or I am doing something else and plain forgot. These situations can be addressed with more planning, and taking working with animals more seriously.

Working with non-rodents, large animals, expensive animals tends to encourage the planning necessary to avoid these problems. It's harder to persuade people, trainees, collaborators, that mice deserve the same respect as dogs. This is part of the PI's job. The time a PI invests in laying down the no-nonsense, we are serious about protocol compliance, and I expect it from everyone, is well worth it.

The IACUC and animal facility at my new place is wonderful. They are reasonable about violations (yes, my lab had one, yes we, me and the trainee, learned from the experience). But I've been places where it's not quite that way. I assure you, finding out that your IACUC has a sadistic streak is not anything anyone wants to do.








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Quote of the Day: Miscellaneous thoughts on government

(by potnia theron) Aug 07 2017

Ninety eight percent of the adults in this country are decent, hardworking, honest Americans. It's the other lousy two percent that get all the publicity. But then, we elected them. -Lily Tomlin
Loyalty to the Nation all the time, loyalty to the Government when it deserves it. -Mark Twain
Nationalism is an infantile disease. It is the measles of mankind. -Albert Einstein
And, as is true of measles, epidemics can be deadly.
It was once said that the moral test of government is how that government treats those who are in the dawn of life, the children; those who are in the twilight of life, the elderly; and those who are in the shadows of life, the sick, the needy and the handicapped. -Hubert H. Humphrey

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