July 5, 2013

The 2013 Lindau Meeting of Nobel Laureates comes to a close: An awesome trip to Mainau Island to conclude an awesome trip of a lifetime

Young researchers and guests, Nobel Laureates and the media converged on Lindau Harbor at seven this morning. Our trip to Mainau Island would begin by boarding ship and setting sail. Jokes flew, “the only way to attend this meeting again is if you win the Nobel Prize!” While low on sleep, the sense that we participants were connected for life did not escape us. We smiled wide and thought deep; we’ve had incredible fun and we have made incredible connections. These past few days were an experience of a lifetime.

On Lake Constance, we soaked in the beauty of Swiss, Austrian, and German country. The scene seemed to smile back. Gelling our experience, we took pictures with new friends, chatted about new ideas, and gained new perspectives. The sun rose on our ship, as it rose on us.

Thank you for reading my blog. Thanks to Mars and Microsoft for helping fund my travel to the Lindau Meeting. Thanks to the Lindau Foundation for hosting me. Thanks to all my fellow young researchers for making this the experience of a lifetime. Thanks to Stony Brook University for providing substantial financial support for this meeting. And thanks to my advisor, Professor Carlos Simmerling, for being an awesome mentor and role-model.


...kevin eduard hauser

July 4, 2013

Part III: How proteins drive biological function through structural change and how scientists drive social change by communicating to the public

In 1988, the Nobel Prize in chemistry was awarded to Robert Huber,
“…for the determination of the three-dimensional structure of a photosynthetic reaction centre.” – Nobel Foundation 1988

Robert Huber delivered the penultimate Plenary Laureate Lecture, entitled “Proteases and their control in Health and Disease,” the take of a Nobel Laureate on the relationship between protein structure, protein dynamics (proclivity to change shape), and protein function. Understanding how to control the function of proteases is a huge problem in drug discovery. Since protein function depends on protein structure (and dynamics), which depends on its amino acid sequence, organisms use proteases to trim amino acids from proteins. By trimming off amino acids from a protein, function is toggled by the protease. With vast swaths of proteases, an organism’s massive menu of proteases acts like a massive switchboard for protein function. When this switchboard of proteases breaks down, cellular function breaks down, leading to disease. Therefore, understanding protease function is critical to developing a way to fix a cell’s broken switchboard.

While Huber’s x-ray crystallography of proteases provides detailed information of protease structure and functional assays yield a general structure-function relationship (needed to develop drugs to control protease function), we still don’t know exactly how to design drugs to regain control of proteases. The reasons for this are complex: protease function depends on the full network of chemistry in a cell. As more research is performed, with new methods driven by intrepid scientists and graduate students, the problem of proteases will be better understood.

Professor Sir Harold Kroto presented the final lecture of the Lindau meeting. Entitled, “Four Horsemen of the 21st Century Apocalypse,” his lecture was all about how profound the need is for science to communicate real knowledge to the public. Making you cringe, videos showed precisely how little the average citizen knows about science. While the lecture illuminated the depths of the problem and challenges science faces in educating the public, there is hope.

Why am I so hopeful? The Internet. It is now becoming easier – and advertisement free – to get information by Google-ing or bing-ing “news” or “what is…” Because you don’t need a TV to access this information, well, a new force driving society to a potentially smarter place is here! Of course, with this new technology come new problems. How will a teenager know an unbiased source of information from a biased source? How will the influence of people with strong beliefs affect these open sources? Questions like these, inspired by Kroto’s lecture, were discussed in the Panel Discussion that followed this lecture.

After lunch, we were off to the City Theatre to attend the “Panel Discussion: Why Communicate?” Moderated by Adam Smith (Editorial Director, Nobel Media AB), quite the group was on stage to discuss the importance of scientific communication: Ada Yonath, Brian Kobilka, Harold Kroto, Beatrice Lugger (Deputy Scientific Director, National Institute for Science Communication), and Simon Engelke. The discussion was very interesting because of the diversity of the panel: Yonath’s lovely liveliness contrasted Kobilka’s calm cool. They argued about the importance of intense competition versus ordered collaboration. Yonath and Kobilka’s view that a scientist’s job is to perform research and disseminate via the usual route, i.e. scientific journals, and let the professional communicators distill that down for the public argued against Engelke and Lugger’s view that distilled communication drives scientific progress by connecting fields to solve big problems. Kroto was on the fence of this research or communicate argument, expressing the need for communication to follow research, treating them as separate endeavors that the researcher herself should partake in. Of course, one would expect the balance of time spent researching then publishing and distilling then communicating depends on the research, the researcher, and the needs of society.

As the panel discussion concluded, young researchers filed out of the City Theatre abuzz with opinions and discussions of their own. From our seat in the balcony, George and I were soaking in the awesome. We began discussing the root question, “What good is knowledge if you can’t communicate?” Sitting behind us were two professional science journalists that overheard our argument and joined in the mini-debate. These two Cambridge men seemed to share quite a bit of interest in the importance of communicating science to the public, as they devoted their careers to bridging the gap between scientific communication and public communication. They both received PhDs in chemistry.

Finally making our way without the City Theatre, George and I ran into Countess Bettina standing at the doors (we didn’t literally run into her). I snapped a picture of George and the Countess, after which I was able to use my humble Deutsch to thank her for making the Lindau Meeting possible.

Grinning ear-to-ear, I made my way to the Evangelical Hospital where Professor Mario Molina was holding a small group discussion. Evening was falling, but no lights were on the room, so only the light of setting sun illuminated the young researchers and the Laureate. This natural setting complemented the theme of the discussion: what can we do to fix this climate change problem? As usual, my fellow young researchers were pointing some important questions at the Laureate. When my turn to question the laureate came, “given the importance of words to describe the severity and significance of climate change models’ predictions, and the statistical analysis of research results as a whole, should not a committee be made to standardize what words can be associated with what statistical numbers?” Interestingly, the answer Molina provided was the shortest of all his answers in that discussion, “actually we’re trying to do that right now.” I can’t wait to see how politicians, scientists, policy-makers, and the public react when relatable meaning is attached to complex statistical interpretation of data! As all good scientific discussions go, ours went way over time, and the group was off directly to the final Lindau Meeting event, the Bavarian Evening at Inselhalle.

At seven in the evening, upon invitation by the Elite Network of Bavaria and the Free State of Bavaria, we converged to an awesome send-off event. Wolfgang Heubisch (Bavarian Minister of Sciences, Research and the Arts) opened with welcoming remarks, Laureate Robert Huber took us on a virtual tour of “Bavaria – Land of Science and Research,” two young researchers presented their research, awards were presented, and a tasty Bavarian Buffet Dinner was eaten well. A Bavarian Music and Folk Dance ensued. The beer started flowing - the best I’ve ever had – to toast to a trip – the best I’ve ever had.

This was so awesome.


...kevin eduard hauser

Part II: Cells recycle old proteins; Redefining the unit of time; Superconductors are cool

2004 Nobel Laureate in chemistry Avram Hershko presented the history of his research resulting in…
“…the discovery of ubiquitin-mediated protein degradation.” - Nobel Foundation 2004
His work, along with fellow laureates Aaron Ciechanover and Irwin Rose, answered the following question. What happens to proteins as we age: do we keep the same proteins we’re born with or does biology break them down and recycle them throughout the course of our life?

Maybe to some this seems like a trivial question, of course cells are constantly breaking proteins down into their constituent components (amino acids) and building them back up. But before Hershko’s work, the question was non-trivial. To answer it, Hershko, Ciechanover, and Rose had to find the mechanism and show how it worked.

A big clue came from Schimke and Doyle in 1970 (Control of enzyme levels in animal tissue; Schimke, R.T. and Doyle, E.; Annu. Rev. Biochem;, 1970) where the rates of protein degradation were delineated. That is, proteins are not only broken down by cells, but the rate at which some proteins are recycled is different than for others.

The big discovery came when Hershko, Ciechanover, and Rose finally pinpointed the tag that cells use to mark proteins for degradation. This tag is actually a protein itself, ubiquitin. The authors discovered more than the tag, though. They discovered the whole pathway that can be taken by a protein during degradation. This discovery has immense implications for medicine and drug companies are really taking notice.


2005 Nobel Laureate in physics Theodor W. Hänsch presented a fun and informative lecture entitled, “What can we do with laser frequency combs?” based on his research…
“…contributions to the development of laser-based precision spectroscopy, including the optical frequency comb technique.” – Nobel Foundation 2005

Admittedly, I didn’t know much about laser frequency combs before Hänsch’s lecture and I was expecting to be blown to bits by a barrage of equations and jargon. But Hänsch totally nailed the lecture. I don’t recall seeing any equations, just really informative animations that conveyed a simple concept so you could understand something a bit more complex. Two slides stood out to me and luckily I was able to video them on my WinPhone.

So what are laser frequency combs good for? They deliver the awesome precision you need to understand why a clock on a satellite orbiting the earth is ticking a little bit slower than an identical one on earth. Why does time matter? When you’re a satellite moving at tens of thousands of miles per hour hundreds of miles above the earth, you experience weird phenomena called relativistic effects, and so the satellite needs to account for that. Without clever math and clever lasers those satellites that our GPSs talk to would be useless – miles and miles off. Of course it is way more complicated than just “clever math and clever lasers” and actually getting it all to work is so hard that you get a Nobel Prize for doing it. As Hänsch put it, you need a “passion for precision.” In fact Hänsch is so passionate about precision he proposed that the definition of “the unit of time” may soon be put to question!

Awesome!


1987 Nobel Laureate in Physics K. Alex Müller was the next presenter of the morning plenary lectures. His contributions to science are numerous but are popularly acknowledged to be for his… 
“…important breakthrough in the discovery of superconductivity in ceramic materials.” - Nobel Foundation 1987

You may have heard of superconductors and imagined a superhero using them to win the day. Superconducting is a quantum effect, meaning weird things happen for weird combinations of metals and oxygen (metal oxides).

Why should you care about superconductors? Well, scientific curiosity of nature and how it works, atom-by-atom, electron-by-electron (physicists takeover from chemists when you get smaller than electrons), can lead to unpredictably awesome advances in technology and thus society. If we can figure out how to make superconductors work efficiently at standard temperatures and pressures using relatively cheap materials, everything electrified will become much more efficient. Since they’re so expensive at the moment, you will probably only see a superconductor at a hospital or a big laboratory. But ten, twenty, thirty years from now, you may look up and see superconductors transporting electricity from a solar energy farm to your home, or in your cell phone, or in the sky driving an as yet not invented machine.

Three more Nobel Laureate Plenary Lectures are to come and sure to be awesome.

…kevin eduard hauser



Part I: How we understand life and climate change has changed, but have we?

At the Lindau Meeting, Nobel Laureates’ lectures have been a lot about the deepest principles of the science that won the Nobel Prizes. In the old but immaculately maintained lecture hall, whose walls have heard the voices of great scientists for decades, I experienced history happening. These are the people who actually changed the world we live in – for the better! So deep and profound an impact on mankind by these men and one woman (an entirely different but profound issue for another yet important day) that their once-new knowledge is now, well, mundanely obviously socially common knowledge.

Awesome.

In this hall I have come to realize my own story on this little blue planet can be an important one. As I myself research the basic principles of how DNA actually works, Professor Werner Arber delivered his lecture, “Cultural values of scientific endeavors,” where I relearned the history of the knowledge that DNA is the code of life. Somehow this was different; hearing the story from Nobel Laureate Arber at the Lindau Meeting with the incredible ensemble of people from around the world with me.

Professor Arber retold the experiment of Avery MacLeod and McCarty in the 1940s that showed DNA was the code of life, not proteins. The experiments that led to this one are largely less appreciated by society as the key step towards our current futuristic state of science and medicine. I reckon it’s the job of my peers and me to be the tellers of the history of science while remaining its sentinels.



1995 Nobel Laureate in Chemistry Mario Molina presented next. He along with Paul J. Crutzen and F. Sherwood Rowland won the prize,
…for their work in atmospheric chemistry, particularly concerning the formation and decomposition of ozone.” –Nobel Foundation 1995

Climate change is real, climate change is serious, and climate change is fixable; if we care to fix it. If we don’t, our lifestyles, our way of life, and the lively state of our planet will perish. We have the technology to fix this potential global catastrophe. Unfortunately, a minute minority of people with great power do not share my view.

A twenty percent probability that sea levels will rise so high that nations and economies will crumble, is twenty percent higher than what I’m Ok with: zero. For only a zero percent probability do we do nothing. Anything above ZERO — well, ladies and gentlemen, it’s go time.

This is an awesome moment in the history of the world.

Let’s do this.


…kevin eduard hauser

July 3, 2013

Part II: “If you love what you do, you never have to work a day in your life.” – Confucius

Dan Shechtman, delivered his lecture “Quasi-periodic materials – Crystal redefined.” He is a crystallographer, but his original adviser was not interested in Dan’s goals. So he quit and joined a new lab. Even Linus Pauling, one of the world’s most respected scientists at the time declared, “There is no such thing as quasicrystals, only quasi-scientists,” about Shechtman. Ouch.

But Shechtman observed, to his disbelief, a five-fold symmetric crystal diffraction pattern. Even in his notes he wrote a huge question mark next to the data. He persisted to test the result and found, to his amazement, that crystals do in fact diffract to an odd-numbered symmetry, and a collaborator’s lab in France, the experts in that field, confirmed the results with highly accurate data. That then led to the Nobel Prize.

Paul J. Crutzen, along with fellow 1995 Nobel Laureates Mario Molina and F. Sherwood Rowland, saved the world. That is, they discovered that nitrogen oxide, spewed by fossil fuel burning machines, depletes ozone in the atmosphere (recall that most of our atmosphere is actually nitrogen, not oxygen). Ozone serves as a molecular sink that absorbs solar radiation that would otherwise cook our planet to an uninhabitable state.

During his talk, “Atmospheric chemistry and climate in the ‘Anthroprocene’”, Paul told us about his serendipitous, unlikely path to the Nobel Prize. In fact, he says, “chemistry definitely was not one of my favorite subjects.” But he loved research, learning, and that was the invisible hand that drove him to greatness.

Kurt Wüthrich’s lecture, due to the thirty minute limit, treated G-protein coupled receptors (GPCRs) saliently. GPCRs are incredibly important for human health and are thus a huge part of drug discovery. Especially resonating with me was his introduction which discussed the importance of dynamics – not just squishiness but wiggliness – to understanding biomolecular function, because biology lives well above absolute zero temperature. That means every single molecule in a cell is wiggling about with energy proportional to the temperature; temperature is simply a measure of the average degree to which molecules wiggle freely. While x-ray crystallography is an absolutely powerful experimental tool, the utilization of which has duly led to a mountain of Nobel Prizes, its data depicts the state of a molecule at a completely not biological temperature.

Wüthrich instead uses 19F Nuclear Magnetic Resonance (NMR), which allows you to determine the structure of a molecule at biological temperature. In addition, it allows you to study the molecule in a solution rather than in a crystal, a further advantage over crystallography. However, NMR still delivers an average structure. Even if the variance is known, molecules with important but undetectably transient states may not be fully characterized.

In any case, Wüthrich lab’s NMR has delineated a detailed story of the subtle structural dynamics of GPCRs as they do their job. Like a Swiss watch, dozens of interacting components work together in a symphony of concerted motions to yield an overall functional effect – instead of the hour hand moving, a bundle of long helices shift the location of kink points. And that is how, we believe, GPCRs do their duty.

It would be tough to say I had a favorite lecture, especially in a public way. But the lecture given by Richard R. Ernst, “Widen your scope by extracurricular activities: My example,” brought tears to my eyes more than once in that thirty minute minuet, leaving a lasting impression onto my scientific soul that I cannot describe in any other way than, religious experience. It was that profound. It wasn’t just the research or the science. It was the humanity. It was the feeling of learning who he really was. Please, I beg of you, watch his lecture on the Lindau Mediatheque.

…kevin eduard hauser

Part I: Tickled worms and a sustainably energized planet

To all my Chemical Biology folks, Martin Chalfie is one cool dude. But it was not he who discovered Green Fluorescent Protein (GFP). Rather it was Douglas Parker in 1992. Martin and his co-recipients acknowledged this fact during their 2008 Nobel Lectures. During his lecture, Martin, a professor at Columbia just over an hour west of us, displayed a timeline of his research on C. elegans, the model organism he has used to study the chemistry of neurobiology. Brining the thousand or so of us at the lecture to loud laughter, the Nobel Prize is just a blip on the timeline of his life’s work.

And that has been the recurring theme throughout the Meeting – that winning a Nobel Prize isn’t a goal, it isn’t the result of one spectacular “Aha!” moment. Rather, winning a Nobel Prize is a pleasant surprise when one simply researches because they love learning.

And then Steven Chu came to the podium to deliver his lecture.

“The energy and climate change challenges and opportunities,” had some content that we US delegates were treated to while at DOE headquarters before departing to Lindau. Solving our unsustainable carbon usage problem will not come with one technology or one policy. Rather, the future of our little blue planet, and thus our own, depends on a global lifestyle change. We don’t need a “fad diet.” We do need a “lifestyle change.”

That means we as global citizens need to make small lasting changes like replacing stupid incandescent light bulbs with smart LED light bulbs. We save energy; we use less carbon; we save money.

That means we smartly turn down the heat or air conditioning in our homes when we’re not home. We save energy; we use less carbon; we save money.

That means we need to think more and waste less so we can live better and our little blue planet can live longer. Doing so will ensure our children have a planet worth living in. Doing so will ensure we will have more money to spend on things like healthy good food and drink, vacations, and lovingly grown flowers for your significant other.

Next was the lecture by Peter Agre entitled, “Aquaporin water channels: From atomic structure to Malaria.” Keeping with the theme of scientific serendipity, he told us all about how in his research that led to the prize, he got data he didn’t fully understand at first. His former PhD advisor advised him to consider that the molecule he discovered, but didn’t know what it was though it was evidently important, may be the long sought, so-called water controlling membrane protein. He tested the hypothesis by removing it from red blood cells, causing them to burst because the force of osmosis (water gushing in) could not be controlled.

…kevin eduard hauser


(Photo credit: Leah Kuritzky)

July 2, 2013

Part IV: A little discussion with Ciechanover and a trip to the casino, I mean, “Applied Statistics Laboratory”

Tuesday evening, 2 July 2013

From the earlier post, What does it mean to be Human, I wrote a bit about the social impacts and public perceptions that we scientists need to consider when personalized medicine becomes widespread, which is within years or less. That is precisely what Ciechanover discussed. Empowered by my nap earlier, I was driven to ask Ciechanover a question that has been on my mind for a while. Just as I raise my hand, and piercingly make eye contact with “Professor Aaron,” he says, “Ok, one last question.” And someone sitting right in front of me, who happens to be a graduate student at Cambridge (UK) also has their hand up. Professor Aaron recommended that we flip a coin to decide. I countered that we play rock-paper-scissor, and since I am unbeatable, I got to ask the question (scissors, by the way). I asked about the way forward for treating disease in light of new science: since cells, especially our own, are such complex networks of interacting proteins producing a spectrum of phenotypes, or diseases, is our current paradigm of controlling protein function by drugging it directly better than controlling protein function by editing the gene that encodes it? My goal was to convey the importance of thinking about treating diseases in new ways, like genome editing, in addition to just drugging the protein that correlates with a particular a phenotype.

Afterwards, I had a break to decompress my thoughts, jot them down, and wander around Lindau with my roommate AJ. We ended up at Lindau Harbor for some ice cream and spontaneous smiling and wonderment. I got a bit of writing done, too.

The final event for the day was the US delegation’s dinner at the Lindau Casino, I mean, Applied Statistics Laboratory. At my table on the patio, some of the US’s brightest drank wine and beer and laughed, really, really loud. At one point, Alisha had the whole table gasping for air, “Tyrone, you had one job to do!” Let’s just say you don’t want to be Tyrone (Guy Ritchie movie reference).

With Austrian mountains dozing in the mist, with a setting sun illuminating the most spectacular oranges and pinks onto Lake Constance, we were well. As the sky turned a darker, deeper blue, we finished our dinner, and joined within.

Robert, `Shak, Allison, and I shared timeless talks on science and life, over chilled white wine, apple strudel, and espresso. Robert snapped a righteous pic of me while I was talking to `Shak about catalysis at surfaces and what on earth the molecules were doing. I can’t wait to see how that turns out, that’ll be an awesome advance in chemistry. Then the big surprise came, or should I say, The Big Steve?

Nobel Laureate Steve Chu made a surprise visit to our little dinner. He intrepidly withstood a barrage of flashing iPhones, and one Windows phone. After spending a magnanimous amount of time with each of our seventy person delegation, the whole group went out onto the App Stat Lab lawn for a group picture. Someone yelled, “Cheese!” and I had no choice but to holler, “Obama!” which seemed by the sound of smiling laughter, to be the right thing to have done.

This is so awesome.


…kevin eduard hauser

Part III: What do Brainbow mice and vegan undergarments have in common? Chemistry.

At 9:30, Nobel Laureate Erwin Neher took the stage as Laureate Ciechanover left it. Professor Neher presented his work on brainbow mice, a play on words that is obvious when you see the image of a mouse’s brain fluoresce a rainbow of colors. These images were beautiful, but they were also very informative. By labeling specific proteins in the brain of mice with different colored fluorescent probes, Neher’s group was able to visualize, with stunning resolution, the activity and structure of a living brain.

In 1991, Erwin Neher won the Nobel Prize in Physiology or Medicine alongside Professor Bert Sakmann,
“…for their discoveries concerning the function of single ion channels in cells.” - Nobel Foundation, 1991

After this visually inspiring lecture, Nobel Laureate Jean-Marie Lehn took to the stage to present “Perspective in chemistry – Towards adaptive chemistry.” The talk discussed effector driven adaptation and amplification – concerted effects of agonists and antagonists, sort of like adaptive networks. This sounds more complicated than it actually is. Here’s an example, for two proteins that work together to perform a function, if you make one function faster, you actually make the other function faster, too, and vice-versa.

Of course if you’d like to see the original explanation and presentation, please check out the Mediatheque on the Lindau website!

http://www.mediatheque.lindau-nobel.org/#/Home

And then it was time to refuel: a brief coffee break to recharge, rub shoulders, and chit chat with one of the most incredible ensemble of people on the planet. Of course the line to get that strong, brilliant German coffee was not short, but it moved quickly enough.

A quick cup, a few smiles and photos, the thought “I can’t believe I’m actually here right now,” and it was back to the main hall for the second set of lectures in the day’s series.

Nobel Laureate Ada Yonath was on stage. I’ve seen her lectures on YouTube before, but hers are the type that must be experienced in person. Her presence and vibe don’t translate to video, even in full HD! After only a few moments, she had the whole hall giggling with silliness.

Of course, she discussed the work that won her the Nobel Prize, but it was the story of getting that data, some of which was obtained at Brookhaven National Laboratory. The trials and the failures, the laughs and late nights, all just blips when she won that piece of information, that data that changed our understanding of the beautiful complexity of nature: how our genetic code is translated into the functional units called proteins. Honestly, the ribosome has the look only a mother could love, a really, really loving mother. Serendipitously, Yonath seems to be the loving mother science, and nature, needed to discover and love the ribosome.

As all good things must come to an end, Ada stepped down from the stage and took the empty seat in front of me, exchanging a quick "this is so awesome" smile.

The next speaker was Nobel Laureate Rudolph A. Marcus. After Ada’s lecture, with awesome visualization of complex biomolecular structures dancing before you, Marcus’ simple slides stood apart, with elegance akin to a calligrapher’s work. For nearly ten minutes, one slide hung before you, a simple diagram depicting two iron atoms, as “Fe”, adjacent to one another, surrounded by about ten slivered triangles representing water molecules. The whole talk, in fact the work that won Marcus the Prize, was to write down an elegant equation to understand how the energy of electrons are transferred between atoms in a solution. That is, how do you write down 1023 pairs of interactions (a hundred billion trillion, or as we chemists call it, a mole), each of which is not simple, in one little equation? According to Marcus, you need: (1) luck; (2) math tricks; (3) to read a lot; (4) reasonable assumptions that cancel many terms at little cost to rigor; and (5) a very simple equation at the end that experimentalists will actually like to test. I’ll try to remember that.

I was falling in love with the nitty-gritty technical details of the science and, somehow, was forgetting that I was being lectured by Nobel Laureates in one of the most beautiful places I’ve ever seen, Lindau Germany. That’s an awesome day dream to fall out of and reality to fall into.

On to the kind of chemistry everyone knows and loves, organic. Richard R. Schrock lectured us next, “Advances in Olefin metathesis employing molybdenum and tungsten catalysts.” That is, use cheap and abundant metals to catalyze the essential chemical reactions that produce the materials of our futuristic, modern lives. Schrock reminded us that his work, along with fellow 2005 Nobel Prize in Chemistry winner Professor Robert H. Grubbs (yeah, Professor Barney Grubbs’ dad), was actually the logical continuation of work that was performed at DuPont in 1956 by H. Eleuterio. Schrock was privy to this “old” work because he himself worked at DuPont and had access to the patents. Although I’m not an organic chemist, I rather enjoyed Schrock’s talk because it was like relearning metathesis chemistry from the guy that essentially reinvented it. If you’re a chemist, you’d understand how awesome that is. If not, trust me, it’s awesome!

Professor Robert H. Grubbs presented next. He’s tall, like Barney. I heard that the two of them like to team up at basketball tournaments at ACS meetings. Totally not fair, but totally awesome.

In any case, I have a rather personal, but indirect relationship with Grubbs. His undergraduate research adviser was Professor Merle Battiste, at the University of Florida. For me, Battiste was one of those instrumental people that challenged me to think differently and better. (Professor Grubbs wrote a nice bit about his experience with Merle) I remember visiting Merle vividly. Mountains of neatly stacked papers enlivened his office like the Himalayas. From his desk drawer, he would withdraw a pipe, pack it with sweet smelling tobacco, strike a phosphorous match, light, and exhale a breath of smoke that didn’t smell too bad. Yeah, that means he was smoking indoors, in a chemistry research facility. While my relationship with Battiste was profoundly important to me, I can only say that I was on cool enough terms with him to call him “Battiste the Beast” as I thought that was the coolest, most fitting nickname ever. He’s gone from our little blue planet now, but his memory lives on, hopefully immortally.

Just in case we young researchers needed more reasons to become the life of a future party, Grubbs reminded us that Victoria’s Secret can manufacture Vegan undergarments because of olefin metathesis organic chemistry. To all my undergraduates out there, you’re welcome for that bit of info!

Time for lunch: I had to pass so I could catch twenty minutes of REM sleep, as I have been getting less than four hours of sleep for the last four days. After a few thousand eye twitches, a cold shower, and some caffeinated beverages, it was off to a discussion with fellow young researchers led by Laureate Ciechanover.

…kevin eduard hauser


Part II: What does it mean to be human?

Plenary lecture by Professor Aaron Ciechanover entitled,

“Drug development in the 21st century – Are we going to cure all diseases?”

What if sequencing our own, personal genomes becomes common practice?

The causes of breast cancer can be complex. EGRF-1, HER-2, BRCA-1 are all proteins in our bodies that upon mutation, can lead to breast cancer. However, a drug only targets one of these proteins, and if the wrong drug is prescribed to the patient, then the patient will see no benefit and their health, their survival, will be compromised. Thus, sequencing of a patient’s genome would allow the doctor to pinpoint the protein that is mutated and prescribe the proper drug to treat the cancer. This is one of the more obvious, practical benefits of “personalized medicine” as Ciechanover defines it. I agree wholeheartedly with this route.

But things can become ethically tricky really quickly when a person’s genome becomes sequenced. What does one do when one finds out that they have a mutation that increases the probability of having cervical cancer? Does one decide early on to surgically remove the tissue? What about having children? Should one first have a child, then remove the tissue? Should one even consider bringing a child into this little blue world with the knowledge that they too will be predisposed to the cancer?

Ciechanover illuminated the story of Angelina Jolie, who decided, after having children of her own and famously adopting others, to remove the tissue that would probably become cancerous. The question is not only about what to do with this information, for one’s own health, but whether to know the information in the first place.

Would it be better to never know one's own disease proclivities? For example, would one want to live out their life with the ever present, potentially painful knowledge that any day, they may find cancer in their body? Further, would one want to bear the burden of knowingly delivering these potentially unhealthy, deadly genes to their children? For example, would it simply be simpler to have children without knowing their proclivities for disease than to know the chances and have the children anyways?

I’ve thought long and hard on this issue myself, though recent science suggests something can be done about my disease, Muscular Dystrophy (MD). I sketched a quick square of major outcomes of having a child, where: 1) my genome could be sequenced; and, 2) a cure or treatment is made available to deal with the disease.

Let’s assume I know I have a genetic disease and the only way to treat the disease is to do so before the child is conceived (i.e., in vitro).

First, I would not treat the child and conceive the child with the knowledge he/she will likely have MD (and that it would make him/her tougher, as it did me), and the two possible outcomes would be: a) she would hate me for knowingly giving birth with a terrible disease; or, b) she would love me for allowing her to learn how to be truly tough.

Second, I would treat her and she would not have the mutation causing MD, and the two possible outcomes would be: a) she would be happy that she did not have to have this disease and know what it is like to run fast (can’t be all that awesome; I wouldn’t nor do I care; I am happy); or, b) she would hate me for curing her, wishing that she had a profound method of toughening up.

As with the style of all the plenary lectures at Lindau, no discussion follows immediately after each lecture. Rather, the Laureates are available during the coffee breaks, Young Research discussions, Panel Discussions, or at a local pub in Lindau later in the day.

After Ciechanover’s lecture, I was very excited to attend the Young Research Discussion section later today. Read on for the next post where I share my experience of the rest of the plenary lectures today!

… kevin eduard hauser

Part I: “How can science drive solutions that better use the planet’s resources?”


Tuesday Morning, 2 July 2013

On my way to breakfast at seven in the morning – “The Science Breakfast: How can science drive solutions that better use the planet’s resources?” – I cross paths with Mahmoud, a presenter from yesterday’s Master Class. It was a bright, warm, blue skied morning; our little group, with three other Americans, clap-clopped our way along the cobblestone roads to the Forum am See hotel on Lindau Harbor. Mahmoud kindly shared some helpful hints about synthesizing and optimizing nanoparticle functionality to serve as vehicles for drug delivery. Apparently, his synthesis method is quite robust in the test tube and the high yielding products rather tolerable in the body.

We arrive with a few minutes to spare, finding ourselves on the second floor of the hotel amongst a bouquet of fellow young researchers perfuming the air with the sound of science and the smell of coffee. Mahmoud and I find a window open to a masterpiece – Lindau Harbor in the morning – and settle our breakfast plates on its sill. Perhaps we chatted only lightly for those five or so minutes because we both understood that words would never do justice to the scene and the sentiment rocking us at that moment: We have been carefully selected from tens of thousands of candidates to help scientific and social elite to help fix the ills of our world. We have been carefully selected to be a part of the dialogue of the future, to help engage the motivations of those whose motivations matter most, and to do all of this here in Lindau.

Nobel Laureate Steven Chu; Chief Agricultural Officer of Mars, Incorporated Howard-Yana Shapiro; Young Researcher Christina Heroven, a Master’s student in biochemistry at Berlin Free University; and, Moderator Adam Smith Editorial Director, Nobel Media AB, performed a most engaging and enriching discussion that was right on topic.

The main topic was that the public, and even some major economists, do not realize higher profits come with using less and thinking more. For example, Steven Chu discussed the massive costs of using much more fertilizer by farmers than is actually needed. Fertilizers are very toxic. Furthermore, fertilizers runoff crop fields and into the rivers and lakes, propagating their toxic impact on ecosystems for thousands of miles. One farmer in North Dakota can have a detectable impact on fisheries in the Gulf. Now imagine how many farmers there actually are in US and how much excess fertilizer, and wasted US taxpayer money, is essentially getting flushed down the river. The counter argument is that it is better to overestimate the amount of fertilizer one needs and see a full yield of crops, then to guess too low and produce too little crops. There is logic in that argument, but the fault is the uncalculated cost on the environment and the inability of such farmers (not all of them of course!) to use science and technology to use fertilizers more effectively, more efficiently, and thus save money!

How large of an impact on our ways of life, as citizens of this little blue planet, and the ways of life for all of nature, will it be if we don’t better develop and deploy science and technology, starting right now?

As other topics were explored by this incredible panel discussion, the theme of intelligent moderation began to boil up. Integrating an intelligent, healthy, moderated lifestyle is key to our future on this little blue planet, from the way we eat to the way we produce food, from the way we produce energy to the way we use it. I cannot completely comprehend, no less explain, how privileged and honored I am to have attended the Science Breakfast panel discussion this morning. Not only to be a part of the discussion, but to know that our generation of burgeoning scientists and chemists are dauntless in the face of climate change, sustainable food and energy production and consumption, and ethical and economical endeavors to drive such change.

We will solve these issues. More coffee, please!

…kevin eduard hauser




Photo caption: Kevin with Mahmoud

July 1, 2013

Part II. Dancing with Science Superstars, eating with Mars, learning from Masters

What does awesome mean? Attending the Lindau meeting is providing so many experiences that can only be defined by the word, awesome.

Today has been one of the most awesome days of my life; and it’s just now time for lunch. But not just any lunch, lunch with Pamela Mars, of the nearly 100-year-old international, family-owned business Mars, and her company’s top scientists and executives. Like yesterday’s dinner, we were treated to some of the best food on Lindau, which is saying a lot. Unlike yesterday, we were asked to ask questions, rather than answer them. It’s not entirely trivial to ask an intelligent question, in a room with very intelligent, powerful people, who just helped pay for you to party like a Scientist in Lindau, Germany. However, it sure is fun. I highly recommend it.

After lunch, I attended the Master Class entitled, “New frontiers in deciphering mechanisms of diseases and in drug development” led by Nobel Laureate Aaron Ciechanover. Although I didn’t get to present my own work at the class, I participated in the discussions of cutting-edge research being performed by fellow young researchers from around the world. The science presented and discussed during this class likely represents the direction we will come to understand as the preeminent, forefront of biomedical research years from now.

Mahmoud El-Sabahy presented first, leading a three-talk series on using nanotechnology to deliver chemistry to the cell. Born and raised in Egypt, his representation of Egypt, which is undergoing rebirth in democracy, was amazing enough. But, as with everything at Lindau, it got cooler. He presented his research on the development of easy to synthesize, highly functional nanoparticles (i.e. that safely transport nucleic acids, enzymes, classic small compound drugs).

Nathalie Busschaert, from Belgium, a PhD student at the University of South Hampton, UK, presented supramolecular cation shuttles that can transport calcium ions across the cell membrane, representing a new paradigm in the treatment of many human diseases in which cells need help moving ions into and out of the cell.

Francesca Re developed and tested a potentially transformative method for curing Alzheimer’s disease by using simple chemistry principles and intuitive biochemistry. With simple synthetic micelles, and armed with a hypothesis that the amyloid fibril plaques in the brain that cause the disease are held together by hydrophobic forces, her simple micelles were able to dissolve the plaques and drive them out of the brain.

Whoa.

A discussion with Brian Kobilka and young researchers
Part of the Meeting includes multiple, simultaneous discussion sessions around Lindau where groups of young researchers can take part in group discussions with the laureates. I attended the afternoon session where students got to ask laureate Brian Kobilka questions. Some asked questions like, what does it take to win a Nobel Prize; others asked questions like, what is the future of drug discovery; I asked about modifying a person’s own DNA as part of medical treatment.

Dancing with the Superstars of Science

To top off an awesome, life affirming day the Republic of Korea hosted an International dinner at Inselhalle with the theme, Blue Chemistry. The Ambassador of the Korean embassy in Berlin, Jae-Shin Kim and Former Prime Minister Hwang-Sik Kim delivered inspired talks on the challenges facing our little blue planet. Serious, deep notions of responsibility to save our planet were discussed: carbon dioxide sequestration, waste cancellation, energy neutrality, and rethinking our role as citizens of nature.

Movingly, opera singers sang, a research professor presented specific aims of Blue Chemistry, and we all ate bibimbap!

After the Korean dinner, we all danced - the polonaise - at the Inselhalle. My dance partner and I were dancing right next to Steve Chu and Countess Bettina Bernadotte. Smiles were wide on every face.

… kevin eduard hauser


Photo caption: The author (right) with Steve Chu (center)

Part I: A Morning to Remember

Today was the first dawn to dusk day of events at the Lindau Meeting. Immersed in the spirit of Lindau: Seven Nobel laureates lecture at the Inselhalle. 1

Plenary lectures, published on the Meeting’s Mediathoque, were delivered by Nobel Laureates Brian Kobilka (2012), Gerhard Ertl (2007, “…for his studies of chemical processes on solid surfaces.”), Akira Suzuki (2010, “…for palladium-catalyzed cross coupling in organic synthesis.”), David J. Wineland (2012 Physics, “…for ground-breaking experimental methods that enable measuring and manipulation of individual quantum systems.”), Sir John E. Walker (1997, “…for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)”), and Hartmut Michel (1988, “…for the determination of the three-dimensional structure of a photosynthetic reaction centre.”).

Amazingly, I was able to slip into the best seat in the house, again, for the morning lectures. Instead of sitting next to Countess Bettina, this time I was sitting next to two Nobel Laureates, Akira Suzuki and Gerhard Ertl. And no, they didn’t sneak a wink of sleep, I checked.


The lectures covered a range of topics from the outlook of drug discovery to founding new principles in catalysis. Dr. Brian Kobilka illuminated current challenges, and ways forward, to discover and develop much needed new medicines targeting G protein coupled receptors. These proteins comprise, by far, the largest set of drug targets pursued by the pharmaceutical industry, and that is primarily because of their central role in signal transduction.

On to the fundamentals of matter, the course of the lectures was driven by Dr. Gerhard Ertl, who discussed the physical chemistry of characterizing chemistry at surfaces, with atomic resolution. That is, he showed movies of actual atoms moving about a catalytic surface — absolutely awesome. Dr. Akira Suzuki presented his cross-coupling reactions, their mechanisms, and uses. If you studied organic chemistry, you know why Akira Suzuki is a Nobel Laureate.

Many people don’t realize it but chemistry led us to the quantum revolution at the turn of the 20th Century. Today, Professor David J. Wineland, the uncle of the quantum computer, described the general engineering and physical principles that make up his quantum computer. With such a technology in hand, ultimately, unpredictably awesome advances in our lives will be enabled.

The fuel of life is the chemical adenosine triphosphate (ATP) and the mechanism of its synthesis via the ATP synthase enzyme in mitochondria was determined by Sir John E. Walker. His talk, entitled, The Fuel of Life, touched on the increasing evidence suggesting that when the ATP synthesis machinery and supply chain breakdown, we age, we get cancer, and we fall into neurodegenerative and neuromuscular states of disrepair. Generating ATP is so fundamental to life, that plants share very similar ATP synthase enzymes, albeit housed in chloroplasts and not just mitochondria. The differences, however subtle, are important, namely the symmetry of the core crank domain, which leads to significantly different ATP generation efficiencies. That is, because of the shape of the ATP synthase, the number of protons needed to generate one ATP is different, which is essential to understanding what fuels life.

The last lecture in the plenary lectures, “Structure and mechanism of Otto Warburg’s respiratory enzyme, the cytochrome c oxidase,” was delivered by Dr. Hartmut Michel. This talk retold the story of cytochrome c oxidase, which began in 1886, but rejuvenated with new tools and more accurate hypotheses. A love story of life, the marriage of oxygen and hydrogen yield water: a force of nature, a force of life, and a force we do not understand, yet. However adventurous, exciting, and profound the story has been to date — over a hundred years in the telling — it is still being written.

Walking my way out of the lecture hall, my trajectory was engaged by the gravity of a constellation of enthused young researchers orbiting Steven Chu. Subtle and smart smiling and eye contact allowed me to penetrate the field; I was able to pitch, in thirty seconds, my crazy idea about electrifying the interstate highway system, solving some big problems at once, but sorting the bill of it, too. I’m not entirely sure Big Steve was grooving to my tune, but he did point to a fault in my proposal, which is what I sought from him. He countered with a solution.

I pause this post at lunch to break up the awesomeness. Read on, as at the end of the evening, I end up dancing, well, and in interesting company!

... kevin eduard hauser

Footnotes: 1. Island hall (German)

Photo caption: The author (right) with Brian Kolbika