Tuesday, August 01, 2017

The Unlikely Road to Here

What does a kid who’s only goal was to go to medical school and be the world’s best cardiothoracic surgeon do when he flunks second semester organic chemistry? It’s not a question I was ever prepared to think about much less answer. I suppose that’s what happens when everything seems to come easy to you, until one day it doesn’t.

In those days at Texas Tech, most premed students majored in biochemistry with a minor in biology. I found myself halfway to a degree in biochemistry with no clue what to do with it when I graduated. The obvious but undesirable answer was to sell drugs to doctors for some big pharmaceutical company – how humiliating for the kid who was going to be the next Michael DeBakey. As part of my degree plan, I enrolled in Undergraduate Research 4000 thinking I would get a taste of the research lab which I somehow envisioned was different than the laboratory coursework I had experienced. This is when my path first crossed with Dr. Robert W Shaw, at least I think it was our first significant interaction. It turned out to be the beginning of a 30-year friendship that lasts to this day.

My undergraduate research experience didn’t turn out as I envisioned. Bob asked me and my two cohorts to forego working in the lab for working in the library. We each had a list of journals and topics that were relevant to his interests and we were to go to the library each week and scan the journals for the topics at hand and bring back citations for any relevant papers. Well, that’s an easy “A.” As it turns out, that undergraduate “research” experience turned out to be critical to my professional development. First, it gave me a broader exposure to science outside of whatever essentials we covered in classwork. Reading those papers opened the world of science beyond the old lessons of the textbook to the frontiers of biochemistry. Second, and perhaps more important, it got me into the habit of keeping up with the current literature and thus the cutting edge of scientific research. Even as I started graduate school and into my postdoc work, I made it a point to go the library each week and scan my favorite journals.

During that year, I decided that instead of pushing pills to doctors, I would go on to graduate school and decided to stay at Texas Tech. My intention was to work with Dr. Shaw and so I started out in his lab. However, when it came time to choose a lab for my doctoral work, my friends and I chose the new professor in the department who worked on “cancer research,” much sexier than enzymology! Bob took this news in stride and agreed to be on my doctoral committee.
No matter your plans, life has a way of working out differently much of the time. Despite my working in another lab on my project, Bob ended up giving me lots of input and advice on my work. It was in his graduate courses where my love of biophysics was born and blossomed, an interest that lasts to this day. But perhaps the most important lesson of my graduate experience had little to do with science and everything to do with ethics in science.

My first project in graduate school involved trying to stop the enzyme that HIV uses to multiply. Since it was an enzymology project, Dr. Shaw was involved with guiding me through the work. It started off well with exciting results, but soon things got complicated and I ran into a seemingly insurmountable wall. I dropped the project and moved on to what became my thesis project. Near the end of my time in grad school, my future postdoc secured, my graduate advisor placed a manuscript for publication on my desk. It contained the work from my first project. However, the data were cherry-picked to support the initial observations and all the negative data omitted. I was told that if I didn’t submit the paper with my name as an author, I could not graduate.  I knew I could not let this stand and went to Dr. Shaw and he counseled me to go to the department Chair. Bob knew the work almost as well as I and understood that this was unethical. My doctoral committee met and decided that the paper could not be published and that I could graduate. It was a scary ordeal for a soon to be Ph.D. and I would not have survived without Bob’s support.

I learned yesterday that Bob is retiring after a long distinguished career. As I sit here at my desk and think of journey over the last 30 years I can honestly say that I don’t think I would be here if I had not had the good fortune to cross path with Dr. Shaw all those years ago. He passed along to me his love for biophysics – how biological processes are controlled by the laws of physics – which led to my lifelong love for how proteins are put together. He taught me how to always ask the right questions, the big questions, the ones whose answers matter. He reinforced that it is always OK to stand up for what is right in science. From him I learned that I should not be the constraint on my own possibilities, that my own little world wasn’t all there is and that I can have an impact in the bigger world.

Bob started off as my teacher, then my mentor, and along the way became a good friend. I have tried along the way to pass along those same lessons to the many scientists who have passed through my various research groups through the years. If I have had half the impact that he has had on my career, then I count myself both successful and fortunate. Thank you my friend for all you have done for me and the many others that have crossed your path. Well done! Enjoy your retirement!

Saturday, September 17, 2016

I quit Facebook

After nine years, I finally gave up on the Facebook. It wasn't a rash decision. I didn't have a fight and run. I'm not hiding from some personal drama. What I know is this, Facebook became a cesspool for me. Perhaps because I work at an agricultural biotech company and also love politics, my newsfeed was overloaded with piss and vinegar. I would be hard pressed to come up with two other areas where the discourse rarely rises out of petty name-calling and sewer-like "dialog." With each passing day, I would refresh my newsfeed and feel more and more overwhelmed. More and more I found myself looking at Facebook and asking myself, what the hell is the point?

A little over two weeks ago, I deactivated my account. "Do you really want to deactivate your account? Perhaps you should just logoff instead." No, I really want to do this. I clicked yes, and just like that my existence on Facebook became more nebulous. I consciously did not delete my account. Much of my life over the last several years is documented there and I don't want to let that all go - too many photos, my kids growing up, the break up of my marriage if you pay close enough attention, and the blossoming and maturing of my life and outlook over the last couple of years. I decided to leave all of that in its digital box, tightly sealed up until a time where I can open it up without the burden of feeling overwhelmed by the ugliness of the world. I also removed further temptation by deleting its app from my phone.

I suppose my post-Facebook experience was not unlike withdrawals from any other kind of addiction. Let's face it, Facebook was my digital crack. I know the chemistry in my brain was reacting to every "like" or notification or comment just like any other reward system. The first day I found myself picking up my phone and scrolling only to come up empty. I wondered what my friends were saying. I clicked on the bookmark only to get a logon screen, which, if activated would reactivate my account and plunge me right back in. Perhaps the hardest was that weekend. We went to visit my daughter who has just moved away for college.  When I travel, I take many photos of my trip and post them all on Facebook in their own little neat album. This trip was no different, except I had nowhere to share the photos. No place where the rest of my family could see my daughter in her new city. So I left them on my phone.

But coming back home, I did not feel I was missing out on anything by not seeing the world through the lens of Facebook. I followed news via Twitter, which I find less depressing than Facebook. I found that I had more time to live in the world that surrounds me, not the digital world. I read more, books for pleasure, and technical literature in my field. I took up painting and have finished my first two small works, both scenes from my trip to Paris last fall with SK. Last weekend I went to visit SK in NYC. As usual, I took photos around the city, capturing the off the path scenes of life that are new to a Texas boy. I did catch myself thinking a few times that it would be cool to share them, but I did not fret about it. In fact, I have found that this week I have not fretted about social media at all. I have felt a calm about things and have discovered a clearer head with which to think about the world around me, the life I lead and the life I desire.

I do miss things about Facebook. I live apart from all of my family. Facebook was a place that allowed us to connect and to keep up with our lives apart. Given that I overshared, they probably miss more than I. I miss the happenings of a few of my closest friends. I know I am missing some cool links to interesting things in the corners of the internet that I no longer frequent. But I am also finding better ways to connect with those closest to me, ways that seem more intimate and healthier than wading through the noise of social media. I am sure that at some point I will reactivate my account and probably filter everything to a more manageable level. But for now, this is good. This is right.

Monday, August 08, 2016

Entropy Monday - transitions edition

Yesterday my boy played in his 3rd all-star game in 4 years. This year he won the skills competition for the fastest runner. This was his finest season to date in his young baseball career.  Last year was probably his greatest improvement as a baseball player, he actually became a baseball player - focused, a student of how to play the game. This year he really worked on becoming a better player. We bought him a hitting net and he hit at least 100 pitches off a tee almost every day during the season. It paid off with a .815 batting average over the season - likely a 400 point improvement over last season (he didn't keep his stats last season, another change this year). His immediate goal is to make the high school team next spring. Longer term, he wants to play in college and perhaps the MLB. Lofty goals, but he knows hard work will pay off now.

My daughter leaves for college in a couple of weeks. She joins the Conservatory of Performing Arts at Point Park University. She has become such a talented performer the last 5 years. Getting into the CoPA is as hard as getting an NIH grant these days. She has dreams of making it to NYC and Broadway and PPU has an excellent reputation in getting their students there. I know she's going to be great. I don't know exactly how I am going to feel about her being gone. The past year because of all of her school and work activities, I have not seen much of her. And yet, her presence is still felt even when we only see her for a few minutes in a day. I guess I haven't thought much about it until now. The times goes by so damned fast.

I have fallen in love with NYC. Five years ago I would find uttering those words unfathomable.  My first visit to see SK, she took me to many of the tourist sites - Empire State, Times Square, Broadway, Central Park - and they were cool. But most visits since, I have gone to see her and not "visit the city." Of course we have seen the city, but the side of the city that's out of the way. I see the NYC that a resident sees - the neighborhoods, the events, the crowded subway. Granted, I am there "on vacation" but still I feel like I am getting an authentic experience and frankly, I love it. I could see myself living there at some point. As SK points out, it's great if you're rich and you can throw money back at all the problems the city sends your way. I highly doubt that will ever be my circumstance. But NYC, you're on my radar.

That's probably enough randomness for one day. I'm off to read a paper on the van der Waals interactions that determine the unique properties of water.

Wednesday, May 20, 2015

His name is Slatts

I first "met" him in September of 2005, the 24th to be exact. I know this because we both blogged at LiveJournal and that's the day he first left a comment on my blog. His comment had nothing to do with my entry, but was in response to the "Current music - Bob Dylan Desolation Row" tag at the end of the blog.
Great song! Did you catch Dylan's performance of this in No Direction Home?
Of course our first conversation would be over music. Slatts was a bass player, played in real bands. I play guitar, alone, in my room, with a cd. But we bonded over an affinity for the same music - old rock-n-roll, blues. This began our friendship - over Dylan and a blog posting.

Our friendship continued to grow over our shared passion for music. But Slatts lived in Massachusetts and so we also bonded over the Red Sox and our love of Maine. He went on vacation in Maine every year it seems, paddling on the lake. Maine is my spiritual home and seeing his photos always made me smile and just a little homesick.

How did I become "friends" with Slatts on LiveJournal in the first place? My ex-wife is a writer and blogged there with her writing friends. That was my entry into LJ and you see, Slatts was an artist - a damned good one. He made the most incredible drawings of celebrities, many of them musicians. Don't take my word for it. You can see for yourself.  His entries often showed the behind-the-curtain world of art in progress. One of my favorite Slatts techniques is his drawing of musicians' heads on other people's bodies. To call him a Beatles fanatic would be understating the word fanatic. One of my favorite examples of this technique is the piece he created by putting all of the Beatles' heads on top of his own body. Slatts became the Fab Four. It's just brilliant.

I grew up in Lubbock, Texas, the home of Buddy Holly.  Buddy was my hero growing up. It was pretty cool to a little kid to think that one of the guys who started rock-n-roll grew up on the same streets as I. A simple kid from a small town in West Texas could change the world. So imagine my surprise the day Slatts asked me if I could take some photos of me holding my Strat while wearing a coat and tie, so that he could make a Buddy Holly piece. Of course it took all of a few seconds to say, "yes!!!" I took the photos as requested but knowing Buddy also played around in jeans and a white t-shirt, I took some of those, too, and sent them all along. And then on February 3rd, 2007, the work was completed. Slatts had made me Buddy Holly! I really cannot describe how awesome it felt to know that Slatts had turned me into my teen idol. He sent along an original for me to keep. Sometime later, Slatts took those photos of me in the t-shirt with my guitar and turned me into Keith Richards. I was always a Stones fan, too. So imagine how it felt getting to be both Buddy and Keith.

As our friendship grew over the years, we talked about meeting up on one of my trips to Boston, catching a game at Fenway, having some beers together, jamming to some old songs. It always seemed that work or life got in the way and we never got to meet up. You see, Slatts is my friend. But we've never actually been in the same place at the same time. The age of the internet created the opportunity to connect with people without ever having to actually meet them in person. I've often heard and even used the term "virtual friends."

A couple of years ago, I found out Slatts had cancer. It turns out it was terminal. He kept working during his chemo treatments, finishing an autobiographical magazine where he told his story with his own illustrations. After his diagnosis, I had a trip to Boston planned. We talked and decided we wanted to get together and share that beer that we had always talked about. But my schedule and the timing of a chemo treatment ruined those plans. "Next time," we said. Two weeks ago, the cancer had gotten to the point where hospice became the appropriate treatment. In that time, I've thought a lot about my friendship with Slatts and all the good times we had. He was such a fun-loving guy, always there with a big smile on his face. We always had something cool to talk about. And, I have a whole collection of coffee mugs with his artwork on them. Slatts has passed on now. In the age of the internet we can make friends with people we've never actually met. As I sit here and remember my friend Slatts, it hurts like hell, as much or more than if we had grown up together in the same town. He was truly my friend, and god, am I going to miss him.

Tuesday, August 12, 2014

Robin Williams and the loss of youth

As soon as I heard the awful news last night, I texted my cousin Alex, "Robin Williams. Fuck."
Almost immediately, I got the reply, "Noooooo!"
"Yep. Suicide"

We grew up with Robin Williams, guest appearances on Happy Days, Mork and Mindy, The Tonight Show, The World According to Garp, Good Morning Vietnam, Dead Poet's Society, Comic Relief. He was our funny man. Alex and I loved The World According to Garp. It's a damn fine movie. But now the funny guy of our childhood is gone. Taken by the awful disease of depression.

This morning, Bryan Ferry's version of Bob Dylan's Dream played on my iPod. As I listened to the lyrics and thought about Robin Williams, I thought about my friends.

While riding on a train goin’ west
I fell asleep for to take my rest
I dreamed a dream that made me sad
Concerning myself and the first few friends I had
With half-damp eyes I stared to the room
Where my friends and I spent many an afternoon
Where we together weathered many a storm
Laughin’ and singin’ till the early hours of the morn 
By the old wooden stove where our hats was hung
Our words were told, our songs were sung
Where we longed for nothin’ and were quite satisfied
Talkin’ and a-jokin’ about the world outside 
With haunted hearts through the heat and cold
We never thought we could ever get old
We thought we could sit forever in fun
But our chances really was a million to one 
As easy it was to tell black from white
It was all that easy to tell wrong from right
And our choices were few and the thought never hit
That the one road we traveled would ever shatter and split 
How many a year has passed and gone
And many a gamble has been lost and won
And many a road taken by many a friend
And each one I’ve never seen again 
I wish, I wish, I wish in vain
That we could sit simply in that room again
Ten thousand dollars at the drop of a hat
I’d give it all gladly if our lives could be like that
 As I thought about the words to that song and the friends I shared adolescence with, I thought about all those times we hung out together in the parking lot of a donut shop at 2 a.m. arguing about stars and whether time really existed. I suppose when you're a teenager, it's not so hard to think time doesn't exist. It seems like all you have is time, even though it's rushing past you so fast you don't even know it. And then your friends are mostly gone - off to college, off to start families, moving away to start their own lives. You walk into the room and hear that one of the constants in your youth has died and you realize that the time you have is precious. It hits you that the best thing that you can do with that little time you have is to cherish those around you, those childhood friends you share things with that you share with no others. Because some of them might well be gone too soon, too. One of mine already is.

If we could simply sit in that parking lot (room) again, we'd raise a toast to Robin Williams, and to each other. I'd gladly give ten thousand dollars at the drop of hat, if we could only do that.

Here's to us, Alex, Bud, Terri, Mel, Mickey Piggy, Ron, Mr. S., Larry, Jackie.

Sunday, April 06, 2014

What becomes of a life?

Perhaps its the intersection of a personal existential crisis and parenting a teenager and preteen that prompts me to articulate the question of what becomes of a life. To borrow from the Jimmy Ruffin hit, What Becomes of the Broken-Hearted:
As I walk this land of broken dreams,
I have visions of many things.

I know I've got to find,
Some kind of peace of mind.
Help me..
Recent events have made me rethink many of the things I thought to be true about my own path. Things that seemed imminent and certain are no longer so. Pathways and passions that were converging seem now nothing more than an oasis. Changing the world and giving a voice to the voiceless just around the corner. It's possible those things are still within reach, but on a different path. Events still to be determined. Complicating the picture is the reinvigoration of a previous passion - one in which I excelled, but with a path just as uncertain. I think, therefore I am, is not enough, but for now it must be.

As I think about where I've been and where I might be going, I can't help but think about my children and what their paths might be. At this point, the world is indeed their oyster. And yet, as I think about how they will soon be off into the world mostly on their own, I can't help but be scared about that prospect. My fear has very little to do with them but more to do with my ability to properly prepare them to be successful.

I suppose the world is changing no more rapidly now than when I was a teenager. My current awareness makes it seem so. I don't recall thinking much about my own future outside of going to medical school and becoming the world's preeminent cardio-thoracic surgeon. So much for the best laid plans of mice and men. I see the same sort of future thinking in my kids and can't help but think it's my responsibility to prepare them for the time when the best laid plans go awry. They are both incredibly talented and intelligent. They both have designs on what they want to do in the world, reserving the right to change their young minds, of course.

I worry most about how to prepare them to take on a world that we can't yet envision. The cost of a college education is becoming such that it is reasonable to question the value. What kind of life can you have coming out of college $100,000 or more in debt with a career that might not pay that much over a several years? What if their talents and passion lead them to career that innovation makes obsolete by the time they start out on their own? How do I help them see the value in their strengths that don't currently fit with their passion? It's easy to say, "do what you love," or "follow your passion," but it seems reasonable that their are limits to that for those who weren't born on 3rd base or didn't win the lottery (we weren't).

Part of my current job involves counseling my team on career development and I've become excellent at it. It's mostly not difficult with people who are already in a career. I have a more difficult time figuring out my own path. I know what I would tell one of my team in my position, but it seems harder for me to do it myself. It's even more difficult for me to figure out what best to tell my children. It's quite scary thinking that I could steer them wrong and cause them to live a less than fulfilling life. I don't know what the answer is. For now I suppose it is best to continue to create an environment where their intellect and talent can shine and hopefully have the foresight to help them find a direction that will be satisfying for them.

I'd love to hear the thoughts of those in a similar position or those who have already been down this path.

Wednesday, March 05, 2014

No Corporate Shill

I'm a scientist at Monsanto. One of the common criticisms leveled at me and my colleagues is that we are biased because we work for a corporation. Aside from despots and dictators, nothing pisses me off more than someone implying that I tossed out all of my scientific training and integrity the minute I walked into the doors of Monsanto. Those accusations do nothing more than show the complete lack of understanding of scientific training by the accuser. As a scientist, you are trained to go where the data take you and no scientist with any morals would create, alter, ignore, nor falsify data in support of a pet idea. Never in my seventeen years at Monsanto has anyone told me what my experiments should show or what my data should mean.

I was directly exposed to scientific misconduct in the early days of my scientific career - as a graduate student. My first project in grad school was working on the inhibition of an enzyme used by HIV to replicate. Our lab was collaborating with another laboratory at Rice University to test some compounds that made up a large natural product that showed the ability to inhibit the AIDS virus. Our initial results were promising and we expanded our screening to similar compounds. Somewhere along the way, the assay became highly variable and I spent several months troubleshooting. After months with lack of progress, I shelved the project and moved on to another one.

 Fast forward three years. I was nearing graduation and had already arranged for my postdoctoral fellowship. One morning I walked into the lab and found a manuscript on my desk. The subject of the paper was the project I had first worked on. As I read through the paper, I quickly realized that all of my negative or contradictory data were ignored to make a promising conclusion about a promising new treatment route for HIV. I approached my adviser and told him that we couldn't publish the paper because he had ignored all of the negative data in writing it. He said he only ignored data that could  be rationally explained away. Having been the only student to work on this project, I knew this not to be the case. The next day before he left for a two week vacation, he left the manuscript on my desk again. The paper had three different title pages - one with my name first, one with my adviser's name first and my name second, and one without my name. I was instructed to choose which title page and mail the manuscript. I was also told that if I did not include my name on the paper, I would not get my PhD.

I went to the member of my graduate committee that helped with that project and told him what was going on. He instructed me to approach the chair of the department, who was also a member of my committee and explain the situation to him. The chairman told me not to send the paper and that as a committee we would go over all of my data and decide how to proceed. When my adviser came back my committee met. It was quickly determined that the paper was not suitable for publication and that my other project was suitable for graduation. I started my postdoc a couple of months later and graduated that fall. My adviser did not receive tenure and left research the following year.

I don't really think that I did anything extraordinary by standing up for sound science. I look around at my colleagues, many of whom I've worked with for years, and I know without a doubt none of them would compromise their science at the orders of anyone. I also know without a doubt that no one would ever ask me to make my data say anything other than what they say. As I reflect on those late days of graduate school, I'm thankful I had that experience and that it has given me a heightened sense of rigor when performing experiments or interpreting data.

Wednesday, October 10, 2012

The 2012 Nobel Prize in Chemistry

Today the 2012 Nobel Prize in Chemistry was awarded to Robert Lefkowitz and Brian Kobilka for their work on G protein-coupled receptors.

How do signals from outside the cell get transmitted into the cell? It's a question that long plagued scientists and the answer underlies many if not all vital cellular processes. It was thought that there were protein receptors on the surface of the cell that recognized molecules and in the process of this recognition, specific events were triggered inside the cell - the action of the hormone adrenaline, for example. In the 1960's Lefkowitz's lab used radioactive hormones to isolate the receptor responsible for the action of adrenaline - the B2 adrenergic receptor. This initial step of isolating the receptor was key in allowing scientists to characterize the biochemical properties of the protein. Isolation of the protein in an active form was not trivial since the receptor had portions outside the cell, portions in the membrane of the cell, and portions inside the cell - it is a transmembrane protein.

In the 1980's Kobilka joined Lefkowitz's lab and set out trying to isolate the gene encoding the B2 adreneric receptor. He was successful and when they analyzed the gene sequence, they realized there were other similar genes - thereby implicating a gene family. As it turns out, there are many genes that encode these protein receptors, all similar in function, but differing in what external signal they recognize and transmit inside the cell. - smell, light, histamine (think allergies), mood, appetite and sleep (serotonin).

Kobilka left Lefkowitz's lab and established his own research group studying these receptors - especially trying to determine their molecular structure. In the last couple of years, his group succeeded in solving the structure of the B2 adrenergic receptor just as a hormone has bound giving new intricate details on how these important signal is transmitted to the cell.

It is suggested that more than half of all drugs act on this family of G protein-coupled receptors highlighting the importance of understanding exactly how these proteins function and opening doors for the treatment of many disorders.

Monday, October 08, 2012

The 2012 Nobel Prize in Physiology or Medicine

The Nobel Committee announced the awarding of the 2012 Nobel Prize in Physiology or Medicine to Sir John B. Gurdon and Shinya Yamanaka for their work on the reprogramming of mature cells to immature pluripotent cells.

It is rather amazing to think that the variety of different cells within our bodies start from a single cell. Those early cells that have the ability to turn into many different types of cells are called pluripotent stem cells. The cellular differentiation process is relatively well understood. But, is it possible for a mature cell to revert to its immature, pluripotent state, or is cellular differentiation a one-way street?

Fifty years ago Sir John Gurdon performed an experiment to test this idea. He replaced the nucleus of a frog egg with the nucleus of a mature cell from a tadpole intestine. This egg developed into a normal adult frog. After subsequent repetition of the experiment it became clear that the information for cellular differentiation still resided within the mature cell. In fact, cells do have the ability to go backward.

After this discovery, the question became, how does this happen? What are the keys to the underlying mechanism of differentiation? In the early 21st century, Shinya Yamanaka took genes thought to play a role in keeping cells in an immature state and injected them into mature cells in varying combinations looking for combinations that would turn those mature cells into immature cells. He and his colleagues did find a combination that reprogrammed these mature cells and surprisingly, it took only 4 genes to accomplish this remarkable task. They went on to show that these reprogrammed cells could differentiate into many different cell types.

The implications of this work are profound. Gurdon's original observation led to the cloning of mammals - Dolly the Sheep being the first success. The ability to reprogram cells by the introduction of just a few specific genes creates cellular tools that allow us to get a better understanding of the underlying processes, the study of changes in healthy versus diseased cells, and even the potential to use these findings to treat degenerative diseases.

There are many unanswered questions about the potential of these reprogrammed stem cells. Dolly the Sheep only lived 6 years and these genetically reprogrammed stem cells appear to have a propensity to form tumors. However, the two discoveries awarded this year's prize have opened up amazing possibilities.

Tuesday, April 24, 2012

Twilight moon

Sometimes it is enough to sit on the sidewalk
and stare at the crescent moon
and Venus low in the twilight sky.

Other times it is necessary to capture
the moment and share with a friend
2000 miles away.