Avidity Blog

Fun

2012-02-10T13:44:00.000-08:00

“Man only plays when in the full meaning of the word he is a man, and he is only completely a man when he plays.” --Friedrich von Schiller
“Play is the highest form of research.” --Albert Einstein
I had the incredible good fortune to work for the company Affymax from 1990 to 1992. Affymax was subsequently gobbled up by Glaxo and re-incarnated as a pharma company. I can’t speak to today’s Affymax, but I can tell you in the early 90’s it was a very special place to work. Many (or most) of the lessons that I try to apply to my current company (Avidity) were from that period of my life.
I think anyone who worked at Affymax in this time period would tell you that it was one of the most dynamic, innovative, and FUN companies in which to work. Certainly it is the scientist’s dream to work on cutting-edge technology, but what stood out for me were the incredibly creative people and atmosphere.
Managing scientists is a challenge (more on this in a later blog). I think one of the things that set management apart at Affymax was the recognition that when you have a very creative group, play is not only healthy but is to be encouraged, or at least not discouraged. I remember a discussion among the scientists in my group (Molecular Biology) along with another group that occupied common space (Cell Biology) about the Coriolis Effect on the direction of spin of water in a sink. The entire group of scientists stopped what they were doing and gathered around the sink to perform a series of experiments where the sink was repeatedly filled with water, the stopper pulled, and the direction of spin of the water was noted as the sink emptied. The experiment was varied by initiating a spin and then pulling the stopper. As this impromptu experiment was going on, a mid-level manager entered the lab, stopped in his tracks, and observed the goings-on. Managers in many companies would have admonished the group to “get back to work.” In this particular instance, the manager, after asking what was happening, simply left without another word.
In another example, the scientists from the optics group commandeered a room and used their expertise to set up an optical solution to viewing a solar eclipse where the eclipse could be visualized on a wall. Management invited any and all scientists to come view the eclipse.
Neither of these activities could be construed as work-related, but both illustrate the connection and curiosity that scientists have of the world around us, as well as the recognition and willingness of Affymax’s management to acknowledge this important facet of our make-up.
I try to encourage that sense of play in Avidity’s scientists. We are fortunate to get to play with luciferase and fluorescent proteins. Now that I am aware of bioluminescence, I see how common it is in the world around me. And when we make and discover these magnificent proteins, I can’t help but comment about how lucky I am that I get paid to have this much fun.

NEXT BLOG: The one I promised this time, but I was having too much fun—“Question Authority”

2012-01-28T18:54:00.000-08:00

People only see what they are prepared to see
-- Ralph Waldo Emerson

“If I had an hour to solve a problem I'd spend 55 minutes thinking about the problem and 5 minutes thinking about solutions.” -- Albert Einstein

“Student: Dr. Einstein, Aren't these the same questions as last year's [physics] final exam? Dr. Einstein: Yes; But this year the answers are different.”

Have you ever noticed how when you are prepared to buy a car, suddenly, there are car commercials everywhere? I’ve noticed the same phenomena when I ask a question in science—now that I am attuned to a particular topic, I see articles and discussions everywhere. It may be that I’m becoming aware of a topic just as the rest of the scientific community is also starting to wrestle with a subject, perhaps because of a recently published experiment that shifts the paradigm and forces us to consider new possibilities. The danger in this, I guess, is the trap that one of my colleagues describes as “group think.” My colleague believes that conferences are NOT good for innovative thinking because the conference group moves toward consensus on a topic as the talks progress. The individuals in the group reach closure on a particular topic rather than keeping the questions open.
The Gestalt Theory of Closure is about how we fill in incomplete information based on the common templates we carry in our minds. The human mind wants—maybe needs—to complete open questions. In Joseph P. Hallinan’s book, “Why We Make Mistakes”, he refers to framework errors, where based on previous information, experiences, or backgrounds we assume a framework for making the decision when the particular situation is not analogous. I see the framework error all the time on the program I like to watch with my kids called “Mystery Diagnosis.” Almost all of the missed diagnoses result from physicians assuming the symptoms they are seeing are familiar, and if the patient does not improve, then the doctor’s answer is often “It’s in your head.” It makes me wonder if the computer Watson would NOT make these misdiagnoses because Watson does not need to make the framework assumptions but can sift through all possibilities.
The topics of questions, and closure, are even more important to me because they offer the only solution to the problem that I have wrestled with for a good portion of my life, which is “How can I get this person to see what I’m seeing?” The Zen masters have it right: The best way to achieve a new perspective--to achieve enlightenment—is to ponder a question that does not have an easy answer --that the framework required to answer the question lies outside the framework of a solution.
In science, the biggest discoveries can arise from pondering paradoxes. The answer to a paradox is often found by a profound shift of paradigm. In biology, I can think on many examples, from a re-casting of the Central Dogma to the acceptance of prions. Questions? Please.
Next Blog: Question Authority

2012-01-20T13:02:00.000-08:00

Truth and Beauty

Beauty is truth, truth beauty, that is all
Ye know on earth, and all ye need to know.
John Keats's "Ode on a Grecian Urn"
Beauty itself is but the sensible image of the Infinite.
Francis Bacon
The search for differences or fundamental contrasts between the phenomena of organic and inorganic, of animate and inanimate things, has occupied many men’s minds, while the search for community of principles or essential similitudes has been pursued by few; and the contrasts are apt to loom too large, great though they may be.
D’arcy Thompson, from On Growth and Form

Scientists throughout the ages have wrestled with the concept of beauty. In physics and mathematics an ugly theorem or proof is looked upon with skepticism. I ran across a book review of Ian Stewart’s “Why Beauty is Truth: A History of Symmetry” written by Martin Gardener (Scientific American, April 2007). Stewart concludes that 1) "In physics, beauty does not automatically ensure truth, but it helps.”; and 2) “ In mathematics beauty must be true--because anything false is ugly." Gardener’s review is a good discussion and gives examples of beautiful proofs that are not true, and some ugly solutions that are.
The concept of symmetry as beauty in physics or mathematics requires a group-- a relationship of the elements to each other so that as the group is manipulated or rotated the relationship is maintained. Symmetry arises out of the connections and relationships of the group. Symmetry is beautiful, not because symmetry in itself is beautiful, but because it allows us to make sense—to see—the connections of the elements. Therefore, it is NOT symmetry that is beautiful, but that we see the connections or the underlying relationships that give rise to the symmetry.
In biology, the symmetry we see is a physical manifestation of the physical principles that give rise to the form. One needs only to look at the spirals of a cone shell, or the intricate patterns in an animal’s coat to see Beauty. D’arcy Thompson’s mathematical treatments of these forms give us a deeper appreciation, and a deeper sense of wonder-- as Bacon describes-“making sense of the Infinite.” Mandelbrot’s fractal, a repetition of a geometric pattern at different scales, really just extends the work started by Thomson. The insight from fractal’s that many of the forms (all?) we see in nature can be replicated by a repeated pattern at different scales really doesn’t inform much of the underlying principles.
Thompson’s reductionist approach “essential similitudes” that all biology may ultimately be explained by mathematics and physics, is something that Thompson acknowledges may not be adequate to explain the complexity of systems seen in biology. How can physics explain self-awareness? Stuart A. Kauffman, in his excellent book “Re-inventing the Sacred: A New View of Science, Reason, and Religion” , takes the reductionist approach head-on and offers an alternative view that is worth reading.
We see symmetry in biology, and this physical manifestation of the underlying principles is beautiful in that we are able to connect disparate organisms, and even see the similar patterns in inanimate objects, because the same principles are working to generate these patterns. But there is a deeper Beauty. My previous Blog talked about the awe that I felt at seeing the evolutionary connections between micro-organisms. There was no symmetry in the recognition of the relationship of convergent and divergent nucleotides. There is great Beauty in recognizing the connections—making sense of the Infinite. And there is great Truth in this Beauty.

NEXT BLOG: What Has Been Seen Cannot Be Unseen.

Awesome Biology

2012-01-06T12:37:00.000-08:00

Awesome Biology

“The most beautiful thing we can experience is the mysterious. It is the source of all true art and science. He to whom this emotion is a stranger, who can no longer pause to wonder and stand rapt in awe, is as good as dead: his eyes are closed.”
Albert Einstein
In my last blog, I wrote about the sense of awe and wonder that scientist’s feel in the course of their work, and how over time we sometimes lose or forget this motivation that caused many of us to choose a science career. I think it’s easier for cosmologists or astrophysicists, than for biologists, to be in touch with these emotions as they go about their work. How could you gaze upon the vastness and complexity of the Universe and not feel a sense of awe and wonder?
But biologists have their own universe that is no less awe inspiring. I marvel at the beauty and complexity of even the simplest forms of life, and more important, the connections and interplay between organisms. One of the great stories of modern biology—a story that is currently being written-- is the interaction of the biome with our human bodies. There is accumulating evidence that our human immune systems are heavily influenced by the commensal bacteria and parasites living in our gut. There is at least one reported instance of parasitic pig worms, Trichuris suis, ameliorating the effects of autism1. There is a good review on a possible link between gut bacteria and cancer that concludes “Gut microbes are increasingly being linked to medical conditions including obesity, inflammatory bowel disease, diabetes, and cancer.” 2
What is even more remarkable is that our cells may be influenced by miRNA’s carried in exosomes from fetuses, from cell–to-cell, and even from the plants we eat.3
How is it than when we look at the boundaries of life on a fine scale that the boundaries become blurred and indistinct? This is not dissimilar to what is seen in the wacky world of quantum physics where connectivity, action-at-a-distance, and the ability of matter and energy to pop in and out of existence blur the boundaries of even the most fundamental relationships in the physical world.
I once had a physics professor ask me, as a biology major, to define life. I gave what I thought was a pretty good answer, until he began to ask questions like “Is a virus alive?” He concluded by saying that if I could not define clearly what I was studying, then I was wasting my time. Perhaps one of the goals of the modern biologist is to create that definition of life.
Next Blog: Truth and Beauty
1. http://the-scientist.com/2011/02/01/opening-a-can-of-worms/
2. http://the-scientist.com/2011/08/01/sharing-the-bounty/
3. Zhang, L., et al., Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2011

Mystery of Christmas

2011-12-16T13:07:00.000-08:00

I am an older parent with young children. With Christmas approaching, I always view the holiday season with some sadness. I lament the fact that the mystery and wonder of Christmas, when Santa and his reindeer really could fly, is a distant memory of my childhood—that something has been lost. I rejoice in the fact that I get to re-live the excitement and the awe of Christmas through my children, but still...
My experience of Christmas seems similar to my experience in the lab. I remember the excitement and mystery of those early days in the lab. I remember the wonder at seeing colonies grow from my streaks of bacterial culture, and from isolating DNA and being able to generate bacteria with new properties. Now I spend a lot of time at my desk and on the internet. But, I recently rekindled some of the wonder and excitement of those early years in the lab while working on a food-safety chip for Beacon Biotechnology.
My task (and the task of my longtime friend and Senior Scientist, Tony) was to design capture probes for the chip that could uniquely identify food pathogens such as Salmonella and Listeria. Looking at regions of homology and the unique sequences in the DNA of pathogenic bacteria--the convergence and divergence of sequences-- reveals the connection of these organisms to each other and their genetic drift from each other over time. It was an exercise of great Beauty.
I thought the emotions I felt in seeing the connections between these bacteria might be unique to me. However, in a conversation with Tony about this project, Tony remarked on the great Beauty that he is privileged to experience in the course of his work. Tony also saw the connections. He lamented the fact that scientists don’t do a very good job of talking about (or never talking about) the profound and maybe unspeakable Beauty in what we do.
This is my first Avidity blog. One of my goals for this blog, besides generating topics of interest and creating a scientific dialogue, is to give voice to the Beauty that we are privileged to see.
Next blog: Awesome Biology