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The Art of Discovery

MARY ANN RANKIN. CHAIR
STEVEN WEINBERG, FRANCISCO CIGARROA, JENNIFER WEST,
DAVID DANIEL, KARL GEBHARDT

Dr. Rankin: Welcome to the Art of Discovery. In something like 20 b.c.e., Virgil said, “Happy is he who gets to know the reasons for things.” The French physiologist Claude Bernard wrote somewhat later, “The joy of discovery is the liveliest that the mind of man can feel.” I asked my husband last night why he went into science, and he said, “Well, because it’s fun.” It’s just fun to be the first to know something you’ve discovered yourself. It’s exciting—even thrilling.

   The French mathematician Poincare said, “The scientist does not study nature because it is useful; he studies it because he delights in it, and he delights in it because it is beautiful.” Marie Curie said, “Science has great beauty. A scientist in his laboratory is not only a technician; he is also a child placed before natural phenomena which impress him like a fairy tale.” And Einstein—always the last word in science—wrote, “All religions, arts and sciences are branches of the same tree. All these aspirations are directed toward ennobling man’s life, lifting it from the sphere of mere physical existence and leading the individual towards freedom.” Discovery is really cool. Of course, another famous Einstein quote is, “Science is a wonderful thing if one does not have to earn one’s living at it.” And he was right there too.

   The topic for the next 90 minutes is The Art of Discovery, or perhaps discovering the art of science. We have with us this morning five outstanding speakers. Actually we only have four. One is on the road from Houston in the snow, Jennifer West. We hope she will make it. She emailed me this morning saying she was leaving and hoped to be here by 11:00. So although she was supposed to go third on the program, she may go last. I will introduce her now along with the others, and we’ll hope that she’ll get here in time to participate.

   You have the biographies for our speakers so I won’t go into the wonderful details that are associated with each one of these people. We have a great lineup, but let me just introduce them very briefly. We will have each one just get up and speak, one right after another, holding questions till the end, and then hopefully have a great discussion at the end.

   These speakers were chosen to give you a kind of sampling of discovery and science, I mean, obviously, discovery and science are very broad topics. We have many, many, many wonderful scientists and engineers and physicians in the state from which we have chosen these five. I think we’ve chosen some of the very best, but we have also tried to give you a sampling of different fields and people from different parts of the state. So I hope you enjoy this variety and I hope that it will spur some good questions and discussions later on.

   Along the way perhaps we’ll learn a little bit about what science is and what discovery is in its various guises, and also why people become scientists. My husband chose this path because it was fun and I agree that the fun, the excitement of discovery, is one of the most thrilling things a person can experience. But if that’s the case, then why are fewer young people in this country choosing this life path than in previous decades? What are we doing wrong that we are not imparting this thrill or the opportunity to experience this thrill of discovery to our young people? Or is discovery simply no longer thrilling to the younger generation? These are questions we all need to seriously consider. We are doing something at the University of Texas that I’m hoping will help address the problem of student interest in science. There is nothing like engaging young people in actual research and allowing them to discover new knowledge themselves, to empower them and to show them what the excitement of science is really about.

   This is a young woman who took our freshman research program, a three-semester program that gets students engaged immediately, with a lot of guidance, as freshmen in true research with faculty members. She is now going to medical school, but while she was here as an undergraduate, she went to Afghanistan, using the tools and the empowerment from her freshman research experience, to do blood sampling for tuberculosis resistance in Afghanistan to help guide the country in determining where they had to use special drugs for resistant tuberculosis. She’s a special example, but this is the kind of impact a research experience can have on young people.

   I hope that we can find ways to impart this kind of experience and excitement to more students and draw more into science than we are currently able to do because we’re certainly seeing a drop-off in interest in science and engineering in our country today, and it is a very serious problem.

   Let me introduce our speakers, as I said I would. Our first speaker, Steven Weinberg, holds the Josey Regental Chair in Science at the University of Texas at Austin; he’s a member of the departments of physics and astronomy. His research on elementary particles and cosmology has been honored in countless ways, numerous prizes and awards, including the 1979 Nobel Prize in Physics, and also in 1991 the National Medal of Science; he’s considered by many to be the preeminent theoretical physicist alive in the world today.

   Dr. Francisco Cigarroa, our second speaker, is the tenth chancellor of the University of Texas System. As you all know, I’m sure, he is a nation-ally renowned pediatric and transplant surgeon. From 2000 until his appointment as chancellor, he served as president of the UT Health Science Center and is one of the most eminent pediatric transplant surgeons in the country. Jennifer West, who I hope will arrive in time to be our third speaker, is the Isabel C. Cameron Professor of Bioengineering at Rice University. She got her Ph.D. at the University of Texas at Austin. She works on the use of nanoscience and novel materials in medical applications. She does fabulous work, she’s a great speaker, and I pray that she arrives in time for you to hear about her work.

   David Daniel is the fourth president of the University of Texas at Dallas. He also received his Ph.D. at the University of Texas at Austin, so this is starting to look like a conspiracy, and I promise I didn’t do it on purpose. He was dean of engineering at the University of Illinois before he came here to take over the presidency at UT Dallas. Karl Gebhardt is the Suit professor of Astronomy at the University of Texas at Austin. He comes to us from the northeast; he’s a Yankee from Philadelphia and Rochester and then Michigan and Rutgers. He is working on one of the most interesting problems, according to Science Magazine, in science today: investigating the nature of dark energy, and he’s going to tell us about that. So without further ado, I will turn this over to our panel members and let them tell you about the art of discovery in their lives, starting with Professor Weinberg.

• • •

STEVEN WEINBERG

Plato thought that the way to discover things about nature was simply to think about it. In The Laws there is an interesting discussion of astronomy. Plato acknowledges that it might be helpful for astronomers occasionally to look at the sky, but this he said is only to focus the mind, the way a mathematician proving a theorem in geometry might draw diagrams to focus the mind, but the real work of discovery in science would be purely intellectual. Plato was wrong about this, as about many other things.

   An opposite extreme view was taken by Francis Bacon, the Lord Chancellor of England under James I. Bacon had much to say about science, which was then just barely beginning to be exciting. He thought that the work of science was purely empirical. It was necessary to do experiments, study everything you possibly could about nature in an unfocused way without preconceptions, and gradually the truth would become apparent. He, too, was wrong.

   The truth, as we have learned over the centuries, is that science depends indispensably on an interaction between theory and experiment or observation, that theory is needed to direct experiments to give them a point, and to interpret the results. Experiment is needed not only to confirm or refute theory, but also to inspire theory. The two go together indissolubly.

   In some fields, in particular in my own field, elementary particle physics, the two roles of scientists have nevertheless become distinct. The requirements of theoretical physics and experimental physics have become so technical and so demanding that ever since Enrico Fermi, there has really been no one who works effectively both as a theorist and an experimentalist. I am a theorist, and so I can only give you a perspective on the art of discovery as seen from theory.

   As theorists, we are inspired by puzzles that present themselves to us. These puzzles are sometimes provided by experimental discoveries. Here is a classic example: At the turn of the 20th century experimentalists sought for a measurement of the effect of the earth’s motion on the speed of light. The earth travels around the sun at about 30 kilometers a second; the speed of light is about 300,000 kilometers a second, so there should be about a hundredth of a percent change in the speed of light depending on whether it is summer or winter, when the earth is travelling in opposite directions. Light was supposed to be a vibration in a medium called the ether, and even if the solar system is moving through the ether, the earth can’t be at rest in the ether in both summer and winter. The effect of the earth’s motion was looked for, and not found. This presented physicists with a terrible puzzle, which (along with some other puzzles) finally inspired Einstein to develop a new view of space and time, the theory of relativity.

   Sometimes, however, the puzzles that inspire us are internal to physical theory. For example, in the late 1950s it became apparent that we had a theory of the weak nuclear force that worked perfectly well in accounting for all existing experimental data on this force. Weak nuclear forces cause a type of radioactivity in which a particle inside the nucleus, say a neutron or a proton, changes into the other kind of particle, a proton or a neutron, and spits out a fast electron. This is also the force that produces the first step in the chain of reactions that heats the sun. Experiments on the weak nuclear force presented us with no puzzles. The problem arose when this theory was extended to other phenomena that, for technological reasons, had not been observed (one such process is the collision of very weakly interacting particles called neutrinos with other neutrinos, a process we’ll probably never be able to observe). When the theory of weak interactions was applied to these processes it gave nonsensical results; it predicted probabilities that are infinite. This was not a profound statement about nature; it was just absurd. Clearly, a new theory was needed, that would preserve the successes of the previous theory, and yet not give nonsensical answers to perfectly sensible questions, even if the questions were about experiments that had not been done and might never be done. I and other theorists worked on this problem in the 1960s, and finally found such a theory. It turned out not to be just a theory of weak nuclear forces, but a unified theory of weak nuclear forces and also of the much more familiar force of electromagnetism, and also of a new kind of weak nuclear force, which was subsequently discovered in experiments at high energy. But it was not experiment that motivated the theory.

   Then sometimes we find puzzles in theories that agree with all observations, and have no internal inconsistencies, but are clearly unsatisfactory because they have too many arbitrary features. In fact, we are in that position right now. We have a theory now of both the strong nuclear forces (which hold quarks together inside the particles inside the atomic nucleus), and the electromagnetic and weak nuclear forces. The theory, known as the standard model, accounts for everything we can measure in our elementary particle laboratories, and gives perfectly finite, sensible answers when we do whatever calculations we like, and yet this theory is unsatisfactory because too many of its features just have to be assumed to be the way they are in order to fit the results of experiment. For instance, the standard model has six types of particles called quarks. Why six types, why not four or eight? No idea. Why do they have the properties they have? The heaviest of these types of quark is about a hundred thousand times heavier than the lightest type. We don’t know where the difference in masses comes from; the values just have to be chosen to fit the experiment. There’s nothing inconsistent about all this; the theory agrees with observation, but we clearly don’t have the final answer.

   There is also a rhinoceros in the corner: gravity is left out of all this. We do have a perfectly good theory of gravity. Einstein’s general theory of relativity, which works perfectly well with regard to all observations that we can make and yet gives nonsensical results when pushed to extreme energies. These are energies that cannot be actually reached in our laboratories, but we can think about them, and when we do gravity presents another puzzle.

   Since the 1970s we have been in the position of having a theory of weak, electromagnetic, and strong forces with too many arbitrary features, and having a theory of gravity that cannot be extended to extremely high energies. We are stuck because no new data has been coming in from elementary particle accelerators that challenges us with the kind of puzzle on which our imaginations can feed. One reason is that Congress decided not to build a large accelerator in Texas, the Superconducting Super Collider.

   We’re hoping for great things now from a new accelerator that is just beginning operations in Europe. It is called the Large Hadron Collider, or LHC. The LHC is a circular tunnel 17 miles in circumference, on the border between France and Switzerland, up to 500 feet below the earth’s surface. In this tunnel two beams of protons will go round and round in opposite directions across the Franco-Swiss border millions of times as they’re gradually accelerated, until finally the particles collide head-on. We hope that by studying what happens in the collisions we will discover new things that either help us to solve our existing puzzles or present us with new fruitful puzzles.

   Just last week the first collisions were observed between these two beams. So far the energy is not high enough to learn anything new, and there aren’t enough particles in the beams to give a good rate for interesting collisions, but we have great hopes for the LHC in the coming few years.

   As I said, I’m a theorist. I don’t work at the LHC. I went there in July, and was shown one of the four huge particle detectors that are located at four positions around the ring where the particles are made to collide. The detector I visited, called ATLAS, was truly impressive. If you think back to the ballroom we were in last night and imagine it tipped on its side, that was the chamber in which the ATLAS detector stood. I really had the feeling of being in a cathedral.

   The experimentalists who will use the LHC rely on skills that I couldn’t possibly match, but I do have a large stake in what they do. I’m hoping that their discoveries will get us out of the doldrums we’ve been in for decades. For instance, there is an extremely attractive symmetry principle known as supersymmetry. It has occupied the attention of many theorists over the last 30 years. There is so far no shred of evidence for it (well, there is one shred, but it’s not a big one). We are hoping that that the Large Hadron Collider will be able to produce new kinds of particles that are predicted by supersymmetry. One of the types of particle predicted by supersymmetry theory could have just the right properties, if it exists, to make up what astronomers tell us is five-sixths of the mass of the universe, the so-called dark matter. (Dark matter should not be confused with the even more puzzling dark energy, which Karl Gebhardt will tell us about. Unfortunately, the Large Hadron Collider will probably not tell us anything about dark energy.) If these particles are detected, it will be a triumph, I suppose, of physics in the Platonic style. We’ll just have to wait and see.

   So we are right now at a watershed in the history of fundamental physics, We hope above all that the indispensable cross-fertilization of theory and experiment that was so fruitful in the 1960s and 1970s, and that has lapsed since then, will again commence. Thank you.

• • •

FRANCISCO CIGARROA

Well, for some of us, creativity is the process of experiment and theory. And in what we call the STEMM disciplines which is science, technology, engineering, mathematics and medicine, collaboration among great faculty can produce some remarkable creativity. When you put creative people together, interesting things definitely begin to happen. All you need to produce the next breakthrough is talent, time, commitment, incentive, and of this, a little money never hurts. Well, that is what we at the University of Texas System are providing. We create the means and the opportunity for talented people to work together on the challenges of our time. More than a few people have asked, “Why, just when you were about to step down as president of the Health Science Center and return to surgery full time, would you accept the appointment as chancellor?” Well, the answer is quite simple. As a physician, my job is to save lives; as leader of the University of Texas System, I, with the great team that I have, can save even more lives.

   And how do we do that? We do that through the education of the next leaders of our great state and of our nation across many disciplines, including medicine. We do that by facilitating research through the recruitment and the retention of great faculty and through the ability to build outstanding laboratories that will facilitate that research. We do that through our health science centers and our hospitals in which our physicians and our healthcare providers cannot only prevent disease, we can also have a healing hand to alleviate human suffering.

   Well, let me begin and share with you stories of two or three individuals who had a profound impact on my life. They intersected my life during my training and the creativity that they fostered actually transformed how we care for so many children with certain diseases that were otherwise fatal. And these are two physicians who actually can demonstrate, I think, with great clarity, the power of translational science—that is a physician seeing a problem at the bedside, taking that problem which is not yet solved back to the laboratory, and then from the laboratory figuring it out and bringing it back to the patient’s bedside with the hope that one can cure disease.

   The first individual who intersected my life is a pediatric surgeon by the name of Dr. Melvin Smith. Dr. Melvin Smith, in 1995, was asked to consult on a small infant at University Hospital at Health Science Center San Antonio. That infant was diagnosed with a severe case of thoracic insufficiency syndrome, and in this case the syndrome was Jeune’s Syndrome. Jeune’s Syndrome is an insufficiency syndrome in which the chest wall of the baby does not grow; that is, the chest is completely encased, the lung can’t grow, and the child ultimate dies of asphyxiation.

   Well, the consult with Dr. Melvin Smith was not in regards to the Jeune’s Syndrome. It was a simple consult, “Dr. Smith, can you please come to the neonatal unit and place a tracheotomy tube because this child needs to be on a ventilator for the rest of her life until she passes away.” So Dr. Smith ended up going to the neonatal unit, examining the child, and said, “This is fairly straightforward.” But the mother asked him, “I know you came here to put a tracheotomy tube in my infant, but the question that I ask for you is what can you do to save my child’s life because I understand a ventilator will not save my child’s life.”

   Let me show you the chest x-ray of an infant with Jeune’s Syndrome. This is the infant who Dr. Melvin Smith saw, and in fact, after he saw the child, who was otherwise entirely normal, and after the question was asked by the mother, Dr. Smith told the mom, “I’m going to figure this out, I will place a tracheotomy tube, but I’ll go a step further and I will

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Figure 1. The napkin conceptual design.

 

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Figure 2. The ribs before and after the procedure.

 

figure out how to actually save your baby’s life.” I may add that prior to 1995, I was a fellow in pediatric surgery at Johns Hopkins Hospital and it was a referral center for many children with this type of syndrome and all we could do was palliative care.

   Well, Melvin Smith actually got together with Dr. Robert Campbell. He was a young orthopedic surgeon with a background in engineering, and Melvin challenged Robert Campbell. “Come on, you can come up with an idea about how to develop an artificial rib that can expand and save this baby’s life.” It was almost a competitive challenge. And so they both got together every day at the cafeteria at University Hospital to try to figure this problem out.

   So this is a napkin conceptual design of how this was created (figure1). Every afternoon they’d go to the cafeteria and they would start at least formulating in their minds what a rib might look like, and then answering the question, “Well, we can put this little rib in this child but that’s not going to allow the chest wall to grow, so how can we place an expandable rib?” And so they ultimately came up with the design to the far right that was ultimately patented and ended up actually being the answer of how to save hundreds of children throughout the world with severe thoracic insufficiency syndrome.

   Well, in this slide you see that original chest x-ray of the baby, and then to the far right what that conceptual napkin design ultimately led to, which is really a picture of the current titanium rib that is currently placed in children with this type of syndrome (figure 2).

   Here is a picture of Melvin Smith and Robert Campbell actually operating on a child with severe thoracic insufficiency syndrome and basically placing and inserting this titanium rib, which then over subsequent time can be easily expanded through a small incision over the subsequent four to six months until the lung completely re-expands. And here is the picture on the far right with the titanium ribs in position, and not only did they expand the lung cavity on the right, but it also fixed the severe case of kyphoscoliosis that this child had.

   Now, in addition, when you do lung volume metrics and actually study pulmonary physiology and capacity, not only did it fix the severe thoracic insufficiency syndrome and the kyphoscoliosis, but in fact, the lung volume and the pulmonary physiology of this child completely improved. And here is a picture of an older child who had thoracic insufficiency syndrome with severe kyphoscoliosis with the titanium ribs in place, and now, to your far right, a picture of the same child with the titanium ribs in place and almost with perfect posture.

   So by bringing together a physician, an engineer, the creativity of a university, Melvin Smith and Robert Campbell developed a titanium rib which is now saving thousands of lives throughout the world for a disease that was otherwise fatal. That’s the beauty of translational science. Another individual who intersected my life was Dr. Tom Starzl, and again, this is an individual who basically became very interested in an otherwise fatal disease and that was severe cirrhosis of the liver. Tom Starzl actually was the father of liver transplant surgery and he really developed the surgical technique and also the techniques and the immunology that we currently use today. But his story was not  straightforward.

   In 1967, Tom Starzl did the first liver transplantation on a child with biliary atresia. This is a disease where the bile ducts become obliterated in the first three months of life, the child develops severe portal hypertension, severe coagulation disorders and really, without a liver transplant, these children would ultimately die. So Tom Starzl did that first operation in 1967, and he did a lot of work prior to that operation, but at that operation two things happened. They didn’t predict the severe portal hypertension that this child had and they didn’t predict how bad this coagulation disorder was, and the child died in the operating room within the first hour of the operation. Talking about the agony of defeat, it was a horrible moment for that surgical team.

   But it did not deter Dr. Tom Starzl. They went back; they figured this out. They figured out the physiology of the coagulation cascade to be able to actually get these children through the operation, and ultimately, the next 10 or 15 children he did survived the operation. But again, there was a huge problem, most of these children would die within the first three to six months. In fact, the mortality was close to 90 percent. And in fact, they said you’re going to have to stop doing this procedure because the outcomes are so bad. The unanswered problem was how to solve the problem of rejection. These children would die of acute rejection of the liver and thus these terrible outcomes.

   Then comes along a young scientist by the name of Dr. Jean Borel, Jean Borel understood that there were real problems in the field of transplantation, and he worked in the laboratory with a pharmaceutical company called Sandoz Laboratories. And at that time Sandoz was trying to figure out are there medicines to try can we come up with new medicines to basically treat cancers, and in fact, can you take a look at a variety of fungi that exist throughout the world and determine to see whether we can come up with a new treatment? So they were really basically going across
the landscapes trying to figure out new drugs.

   Well, Jean Borel really loved Norway. He would take lots of trips and hike there. He came back one day to the laboratory with a collection of small amounts of fungi and he found, one fungi called Tolypocladium flatum. He began to study fungus and what he realized was that it had these incredible  immunosuppressant characteristics, but one that was specific and would not immunosuppress the entire body. So he ended up actually discovering a drug called ciclosporin and it was ciclosporin that was the answer to rejection where then in 1983, liver transplantation became the therapy of choice for individuals with liver disease that otherwise would be fatal.

   So now the surgical technique was prepared. We had immunosupressioncigarroa 3
Figure 3. Twin, one in need of kidney transplant.cigarroa 4
Figure 4. The twins in recovery .

but we still had a problem. Here are two identical twins. To your right is an entirely normal child; her identical twin has biliary atresia, and as you can see on the left, her little belly is very tense, full of ascites, and also you can see these little veins that are the result of portal hypertension (figure 3). The problem is that in order to be able to transplant her twin, there was a size match disparity. There really aren’t a lot of individuals who become brain dead who can donate their liver to a child that size. So these children were dying in front of everybody’s eyes because of a lack of adequate-size-match livers.

   Here was another surgeon who told a mother: “I’m not going to let your child die in front of me. I’ve got an idea. The liver has different segments; each segment has an artery, vein and a bile duct; we just need to figure out how to actually resect a segment of the liver.” So he got together with an anatomist and they figured this out in the laboratory, and here you see the dissection of what we do in the operating room now where you can actually resect a segment of the liver where that small segment can go into a baby and the larger segment into an adult, so one donor is now saving two lives. So here we are actually connecting the artery of that left lateral segment into a baby. Here is a picture of the twins after the procedure (figure 4). So again, it is the power of bringing a clinical problem to the bench and then taking it back to the bedside and changing the way we take care of children.

   So what these examples demonstrate is the capacity of talented people to work in collaboration; the power to truly overcome remarkable challenges. And Dr. Smith, Dr. Campbell, and Dr. Starzl all worked at universities of higher education and each made tremendous contributions to our reservoir of knowledge and our capacity to save lives.

   Well, as the largest university system in Texas, the University of Texas has a special responsibility to our students and to the people of Texas to provide an environment that allows this kind of creativity and innovation to take place every day. Recognizing this mission, the University of Texas System created a competitiveness initiative which is an historic $3 billion Figure 3. Twins, one in need of liver transplant. Figure 4. The twins in recovery. commitment to building the most competitive science, engineering and  technology and health infrastructure in the nation and to retaining and recruiting world class faculty and students, the human capital that makes our commitment worthwhile every day when we come to work.

   In the three academic years that the initiative has been in place, we have added or renovated more than three quarters of a million square feet of clinical research, classroom and laboratory space with almost six million square feet coming on line by 2013. We’ve completed 12 of 40 major capital projects such as the UT Austin Dell Pediatric Research Institute and the Galveston National Laboratory at UTMB.

   Our institutions have already recruited or retained 200 outstanding faculty members through a Stars Initiative Program. One is a Nobel Laureate; seven are members of the National Academies, including four newly recruited faculty members. Virtually all of these faculty members are doing the kind of high-quality work that Dr. Melvin Smith or Dr. Tom Starzl have done, and they will become our future Nobel Laureates and National Academy members.

   The competitiveness initiative is really the tangible manifestation of our commitment to excellence. We deserve nothing less, and it sends out the message that the UT System will accept nothing but the best for our students and we will be global leaders in the advancement of humanity and the public good. We have a saying about the University of Texas System: nine universities, six health institutions, and unlimited possibilities. And I truly believe that because of the wonderful discoveries taking place on our campuses. We know that the impact of the University of Texas System on our world is immeasurable because of the unlimited possibilities that it creates. How can you measure that one of our physicians advanced in his or her quest to cure a young person’s disease; how can you quantify that a life was saved today in a device one of our physicians developed or someone learned something that changed the way they view the world; how can you enumerate that a professor gave a word of advice that changed that student for a lifetime?

   Well, we know that as we open the doors for first generation students, we are also educating the next generation of leaders and planting that seed for future Nobel Laureate discovery. We gladly accept our responsibility to inspire our students and to create and we anticipate that their achievements will in turn inspire our gratitude. It is an incredible privilege to serve as chancellor of the University of Texas because it is one of the great institutions of higher education in the world and coming to work every day with the mission of enhancing education, creating new knowledge, providing outstanding healthcare through our hospitals and through our health science centers, and of course, through community service is a mission that inspires me every day. Thank you.

  • • •

JENNIFER WEST

We have been doing quite a bit of work developing a new type of cancer therapy using particles we call nanoshells. You can see a cartoon of one here on the bottom right; it looks basically like a malted milk ball with a spherical core nanoparticle, which we can make out of any kind of non-conducting material, so silica or just glass is a very easy one. Then we need a very thin coating of a metal on the outside surface, and we generally choose gold just because of its very high biocompatibility. It’s generally the most biologically acceptable of all the metals. We can make these particles and if we’ve designed them appropriately, we can have them very strongly absorb infrared light and convert that light to heat.

   One of the reasons this is interesting is because there is a range of infrared wavelengths that are not absorbed by tissue. You can shine this light through tissue and it will pass harmlessly through. If we design our particles so that they will accumulate at a tumor site, then when we shine this light from outside of a patient’s body, it passes harmlessly through the skin and all of the normal tissue, but when it gets to the tumor site, you have localized heating so that you can destroy the tumor cells in that vicinity.

   When we look at what we do to try to accomplish this, we start off with the materials. These materials called nanoshells were originally invented by Naomi Halas at Rice University, and as I’ve said before, they’re this core shell structure and what makes them special is that we have highly tunable optical properties. You saw before that when we use gold colloid, solid gold nanoparticles, we get a bright red color. That is a phenomenon called plasmon resonance, and as scientists have started to  understand that phenomena, they have been able to develop a kind of the mathematical understanding of what’s happening. It has created the possibility to go in and design materials; instead of just going from gold to red, you can manipulate and place the optical properties anywhere that you want them.

   This is an example here where we’re looking at four different batches of nanoshells that all have the same size silica core, but we grew different thicknesses of gold shell around the outside. So you can see as we go from a 20-nanometer-thick shell to a five-nanometer-thick shell, we see a change where this optical extinction curve is and that basically tells us about what color our particles were. We can also, through our particle design, control whether we have scattering, basically light reflecting off at this wavelength, or whether we have absorption, which leads to heating.

   This shows what those particles actually look like, kind of translating those curves into something a little more intuitive. On the far left we again have this gold colloid, solid spherical gold nanoparticles, and then moving from there from left to right, we have a series of nanoshells where we get progressively thinner shells. We’re going across the visible region of the spectrum and out where the particles start to look clear; we’re out into the infrared region of the spectrum where our rods and cones can’t detect that color any longer.

   I mentioned that we want to work in the infrared because of the fact that tissue is transparent there. Tissue is transparent there because you get above the absorption of chromophores, like hemoglobin and melanin, but you stay below where water starts to actually absorb light. You have this window of space here where you have very, very deep penetration of light through tissue, over 15 centimeters, and if you can make your particles have orders of magnitude higher absorption of light, you can start to pass harmless light through tissue, but generate localized heating at the particles.

   When we make these particles, it’s a three-step process where we start off making the silica core nanoparticles, and on the top left we have an electron microscope image of these particles. We have very nice little spheres of glass. We take these and we functionalize their surface with amine groups, and what that does is it gives us positive charges on the surface of our particles. We can use that to electrostatically absorb very small gold colloid particles. The very small gold nanoparticles have a negative charge, so when we put the two together, they’ll associate and we’ll have tiny spots of gold on the surface of the glass particle. We use these as nucleation sites so that we can grow additional gold onto the surface and form a complete shell. That process is shown in a series of electron microscope images where on the far left we have the particle that just has the small gold nanoparticles interacting through the positive and negative charges. As we move to the right, we’re progressively reacting more gold onto the surface and those islands are growing and starting to coalesce and form a complete shell. One of the nice things here is that we have computer models that we’ve built that allow us to predict what size core we need and what size shell we need to get whatever optical properties we need for a new application.

   When we look at cancer therapy now, the idea is that we’ve got particles that strongly absorb light in the infrared and we can decorate the surface of these particles with things like peptides or antibodies that will recognize markers on tumors or tumor vasculature. We can inject these particles intravenously, and allow them to circulate in areas where you have tumor growth. You have very leaky blood vessels, which helps them accumulate at that site, where they can recognize markers on the cells at that site. Once they’re there, we can apply the infrared light from outside the patient’s body. It passes harmlessly through the normal tissue and it hits the nanoparticles; they heat up and hopefully lead to destruction of the tumor cells.

   Looking at some of the animal studies for this, we can grow human tumors in mice and then we can inject the particles intravenously into the mice. After two hours, allowing time for the particles to get to the tumor, we can shine the infrared light and hopefully treat the tumor. What we see here is an MRI of the hind end of a mouse who had two tumor sites. We injected the particles and were shining infrared light through the whole mouse. The colors changes at the two sites were the tumors heating up. I think we’ll just finish without the slides real quickly here—the two tumor sites were able to heat up and reach temperatures sufficient to allow complete destruction of the tumors. The normal tissue in between those sites didn’t heat up at all and wasn’t damaged by the process.

   We were able to track those animals and see what happened; we saw in 100 percent of the nanoshell-treated animals that we had complete regression of the tumors and the animals continued to live for a full year, to the completion of the study, with no tumor re-growth in any of the animals. The control animals with just the tumor growth all died due to excessive tumor growth within three weeks of the treatment date. So we saw very significant results.

   We’ve taken that now to clinical translation. We founded a company, Nanospectra Biosciences, which has built the manufacturing facilities and gone through the FDA regulatory processes and now has the nanoshell cancer therapy in human clinical trials at five different sites within Texas and Louisiana. We are hoping to be able to extend this into many different types of cancer and are hoping that this will significantly impact this disease and save lives. Thank you very much.

 

• • •


DAVID DANIEL

 

Well, we’ve seen some excellent examples of discovery and the art of discovery. I’d like to talk about the infrastructure of discovery, the globally competitive environment for discovery, the race to see who wins in making the most important discoveries of the future. And because this is the Philosophical Society of Texas, I’d like to take stock of Texas’s relative position competitively in contributing, I hope disproportionately, to those future discoveries.

   Perhaps you’ve all seen this map of the world at night depicting population distribution, but obviously it’s really a measure of electricity use at night. My question to you would be what would a map of the world look like if rather than looking at intensity of light, we were looking at the intensity of discovery or where the most intensive points exemplifying the art of discovery at its finest might be?

   Well, Richard Florida, who wrote a book entitled, Rise of the Creative Class, also wrote one of my favorite articles, sort of as a counterpoint to the world is flat and he argues that the world is spiky. And in fact, the hypothesis that I’ll carry forward in this talk, much like the world is spiky in terms of distribution of light, is that it’s also quite spiky in terms of distribution of discovery. A few places are home to a disproportionate number of discoveries in our world. And so this map from Florida’s paper shows where the scientific citations of the world are most concentrated and you can see they’re principally in the United States and Europe and a few other places. This is about a decade old, by the way, and I think if we were to somehow fast forward to a map of today, we’d see much more intensity in Asia than we see represented on this map.

   Florida also compiled a map of patents because discovery doesn’t only occur in universities where we write articles for the open literature. Discovery often occurs quite significantly in the private sector where proprietary discoveries occur that translate to patents that ultimately lead maybe to the infrared cancer-attacking technology such as we just heard in the last talk. But, you can see that indeed there are places around the world that are spiky, that is, where a disproportionate number of discoveries occur.

   Let’s look at Texas and ask ourselves the question: what is our relative competitive position in the world with respect to discovery? Well, one of the factors, I believe, that is quite important to think about is the role of the world’s premier research universities. In North America the Association of American Universities, or AAU, is the “club” of most of the great research universities. I find it really interesting that this club of 60 universities is actually relatively small in terms of the total population of universities in the United States, There are more than 4,000 colleges and universities in the United States, and the 60 U.S. AAU institutions actually comprise only 1.5 percent of the universities in America.

   And by the way, there are three of them in Texas. We have three of the 60 American AAU institutions in Texas, or 5 percent of the nation’s total. By the way, we have 8 percent of the nation’s population and growing, but we only have 5 percent of the nation’s AAU universities. So we underperform in terms of being home to the great research universities of the nation. But, I find it fascinating that 57 percent of all the federal R&D in America goes to the AAU institutions, which comprise just 1.5 percent of the universities of America. These AAU universities are home to more than 80 percent of all the members of the National Academies that are in academe in the United States; 70 percent of all Americans who have won Nobel prizes are affiliated with an AAU university.

   I didn’t put it on the slide, but it’s striking that nearly half of all the Nobel prizes ever awarded world-wide have been awarded to individuals affiliated with AAU universities. And although the AAUs are home to only 6 percent of the undergraduate students in America, they’re home to 63 percent of all the National Merit Scholars. Put another way, the AAU universities are the crown jewels, if you will, of higher education in America and maybe even throughout the world.

   One of the important things that we, at least in academia, don’t think about very often is venture capital. Venture capital is a teeny-tiny piece of the American economy; it’s only $30 billion per year in a $14 trillion-peryear economy. And I guess you would describe venture capital largely as the economic manifestation of the art of discovery; that is to say the intersection between discovery and actual implementation in the private sector, or the commercialization of discovery might be another way to put it.

   Curiously, though, 11 percent, I think it is now, of every American who has a job works for a company supported by venture capital and 21 percent of America’s gross domestic product of $14 trillion per year comes from companies supported by venture capital, and by the way, that’s up 3 percentage points from two years ago. From 2006 to 2008, job growth in companies started by venture capital grew at a rate almost ten times greater than job growth in the American economy as a whole. So if you ask the question where are the new jobs being created, to a significant extent they’re being created in companies backed by venture capital. If you backtrack, well, where does it all start? I think it starts  disproportionately in the spiky areas with the great universities of the nation and the world.

   I’ve compared Texas to just a couple of other states in the bottom slide. These percentages, by the way, are percent of U.S. productivity or population. California has 12 percent of the U.S. population; it earns 18 percent of all federal R&D expenditures. Californians thank the rest of the nation for sending their tax dollars to California to fund their universities. California is home to 30 percent of all the elected members of the National Academy of Sciences, and interestingly, 50 percent of all the venture capital invested in America goes to California; 50 percent goes to California!

   Massachusetts, the state that’s home to only 2 percent of the American population, garners 5 percent of federal R&D expenditures. So they, too, thank the rest of the nation for sending them their tax dollars. Massachusetts is home to 15 percent of the National Academy of Sciences members and receives 11 percent of all the venture capital in America. Massachusetts: 2 percent of the population, 11 percent of venture capital.

   How does Texas do? We’re 8 percent of the American population and growing. We get 5 percent of federal R&D expenditures, so we underperform relative to population share. Texas is home to just 3 percent of the National Academy of Sciences members of the nation, and we only get 4.5 percent of venture capital, and falling, actually, in terms of the fraction in the U.S. We underperform, I would say, as places where the art of discovery is best practiced.

   Even within the State of Texas we’re spiky. Dallas-Fort Worth, for example, has 26 percent of Texas’s population and produces 31 percent of Texas’s gross product. Dallas-Fort Worth garners a respectable 28 percent of the venture capital. The really interesting place is Austin. Austin is the spike. Austin has 7 percent of the Texas population and produces 6 percent of Texas’s gross domestic product, but it attracts 55 percent of all the venture capital invested in Texas.

   Curiously, Dallas-Fort Worth, Houston, and San Antonio combined, are 70 percent of the Texas economy, but Austin gets more venture capital than DFW, Houston, and San Antonio combined. Why? The answer is very simple: UT Austin and the incredible mass of creative discoverers that one finds here in the City of Austin. And for those of us in DFW, as we take stock of what we need to continue to be competitive, it’s not lost on us that creating more great universities would be a good thing for the DFW area. So I would argue that Texas is very spiky, and thank goodness for Austin and for the discoveries and the creativity and the venture capital that comes to Austin.

   One thing that some people don’t realize about Texas is that as a result of having relatively very few top-quality research universities, Texas actually exports talent to other states. According to the IPEDS data, in 2008 Texas exported 11,500 high school graduates to doctoral-granting universities in other states, and we imported 3,700 students from other states to doctoral-granting universities in the State of Texas. We were a net exporter of 7,800 per students per year in 2008, which is about twice what it was in the year 2000.

   So we are shipping off, disproportionately, our best and brightest young future discoverers to other states. It’s wonderful that some of our children go to Harvard and Stanford and so forth, but wouldn’t it also be wonderful if more of the best and brightest from around the nation and around the world came to Texas to make their discoveries right here?

   Just to put the net loss of 7,800 high schools students per year to other states in perspective, the freshman class at UT Austin is a little over 7,000 and the freshman class at Texas A&M is about 8,000, so put in practical terms, we are shipping off the freshman class at either UT Austin or Texas A&M each year and every year to other states to go to their universities. Some of those kids will come back, but many of them won’t.

   So let’s review the situation. Research and venture capital are the fuel for discovery, growth and prosperity. To create wealth, we used to invest in factories with smokestacks. Right? We’d build a new automobile factory. In today’s and tomorrow’s world, we invest in producing brains, that is to say people who are deeply engaged in the art of discovery. Texas is exporting our tax money to other states to fund research at their universities. Or really it would be more accurate to say those other states are earning those resources through their investments in universities. And as a result, other states are proportionately attracting more top faculty, more students, and more venture capital than is the State of Texas. In terms of promoting discovery in Texas, I simply ask the question: is this a smart investment strategy for Texas’s future; does this maximize discovery in Texas?

   Well, let me close with this slide. You know, things are going great in Texas and I’m so happy I’m here and not in California and not in Massachusetts. But let us realize that the world does change over time. This slide shows the 6 largest cities in America 90 years ago, in 1920, which is just one lifetime ago. The largest cities, in descending order, were: New York City, Chicago, Philadelphia, Detroit, Cleveland, and St. Louis. Things were going great in St. Louis and Detroit, and they’re going great in Dallas-Fort Worth right now. But current success does not assure future prosperity. Just ask people about that today in Detroit or Cleveland.

   In the past, I think the keys to prosperity were seaports in strategic locations, rail hubs, and perhaps most importantly, access to natural resources in the vicinity. I think now and in the future, the keys to prosperity are spikes, spikes where discovery all comes together, built around universities and medical research facilities that attract smart people, create environments where the art of  discovery occurs in such beautiful manifestations such as the examples that we’ve already heard, and that then leads to entrepreneurship and constant reinvigoration of the economy.

   So the art of discovery is wonderful for me as an engineer, for scientists, for doctors, just for its purity and beauty, but I would also argue that it may well be the single most important facet for the quality of life in this state and this nation, for our children and grandchildren. Thank you very much.

• • •

 KARL GEBHARDT

It’s a pleasure to be here today and now I want to back us up a little bit. I want to back us off of our planet and out of our galaxy, and I want to talk about the universe a bit. I want to talk about a problem, a problem that we face in science now of dark energy. It’s considered one of the, if not the greatest, problems that exist today.

   The problem we have devised in an experiment here at Texas is called HETDEX: Hobby-Eberly Telescope Dark Energy Experiment. Our focus is dark energy, and let me connect it a bit to what we’ve been talking about. We’ve been working on this for a long time, probably close to five years now. We probably have another maybe four or five to go, so a long time frame. Why I wake up in the morning is to attack this problem. I’ll explain how we’re going to solve the problem here in Texas. It is a remarkable opportunity that we have.

   We get lines of undergrads trying to work on this project when we have a job ad for a mechanical engineer, an electrical engineer, or a computer programmer; we get these remarkable candidates. We are choosing the best of the best. The team that we have assembled for this dark energy experiment, for this astronomical experiment, is just fantastic. I’m so excited to be a part of it, and I wish I could expand it.

   And so my idea and goal is in the science, but there is a remarkable hook here, not just a hook to get people in the science, that’s obvious. But the appreciation for science; the appreciation for trying to understand the universe that we are living in is remarkable to engage the public in science and to get people involved. And that is why we push what we are doing continuously throughout the state of Texas and the country.

   So let me tell you about what we’re doing. We have this experiment; so let me talk about dark energy for a bit. It is, as I said, one of the biggest mysteries in all of science. The problem is what we’re talking about and I’ll show a few plots in a moment. Dark energy may represent over 70 percent of the energy that’s in the universe, and we have essentially zero idea as to what it is, and that’s the remarkable thing.

   So this is a program that we started here at the University of Texas. Gary Hill and I, we’ve been working on this for a long time now. We teamed up strongly with Texas A&M and so we have a very close collaboration now, and we have a couple of partners over in Germany and at Penn State. It’s a relatively small project for what we are trying to do.

   The problem is the universe is expanding and we don’t understand that. The idea of the universe expanding has been around for a while, since Hubble, but in fact, it’s expanding at an ever and ever faster rate; in fact, it’s accelerating. So how big the universe is, how big the visible universe is and the space between the galaxies on very large scales is getting larger and larger every year; it’s accelerating.

   And this is the problem. I have a simplistic equation on the bottom here. And if you want to talk to me about it, I will ask you about a few of the terms here to make sure you know what we’re talking about. I put this up here, not to test you, but I put this up here just to show you it’s relatively easy what we are doing. And so just let me walk you through the very simplistic terms of what we are doing.

   The term on the left, that’s the measurement we make; that’s the expansion rate. It’s not that hard. You go and you look at a galaxy; you see how fast it’s moving. You look at a galaxy that’s a little bit farther away; you see how fast that one is moving. And you keep on and you begin to build up a picture. You begin to build a picture from, “Okay, if the universe is this big, how fast are the objects at that position; how fast are they moving away from us; how fast are the ones here, how fast are the ones here?” And it turns out that the objects that are farther away from us are moving away from us farther. The only way for that to be is the expansion of the universe, and this was talked about by Hubble back in the 1920s.

   But now when we do a really fine measurement, it turns out that the expansion rate, how fast we’re expanding out is changing over time. If you look at the equation on the bottom, it’s pretty easy to calculate, at least we thought it was. We thought it was pretty easy to calculate how to understand the expansion rate. There’s the term on the left; that’s how fast you’re moving. That’s the observation. The first term after the equals is just the matter in the universe.

   Well, so we had this idea of the Big Bang. Everything starts out as a point source in the middle. Most people have heard of the Big Bang: you take all the matter and energy in the universe, squeeze it down to a small spot in the middle, and a long time ago it explodes and things begin to move out. Well, the only thing that we know that can stop the expansion of this giant explosion early on is the mass that’s inside of the universe. There is a gravitational force and the gravitational force tries to act on all the mass in the universe, and so as the universe expands out, the mass should be trying to pull it back in and slowing down that expansion. It’s very easy: you have mass; you have the laws of gravity; they should be able to pull things in and cause it to slow down.

   We want to know if the expansion rate is related to the amount of matter in the universe. It’s a very simple calculation; it’s related to the shape of the universe. That’s a detail which I don’t need to talk about, but it depends if our universe is flat or has a little bit of curvature to it, It has to do if the distance between two points is a straight line or not in our universe.

   And then what happens is we made this measurement: you take the observables, you calculate the amount of masses in the universe, and you say, “Aha, we’ve got a problem here,” and the problem is that our universe is expanding much faster than we think. So we add a term on the right all the way at the very end. It’s a fudge factor that Einstein invented himself; a fudge factor such as the stuff I used to do in my exams in college. If I couldn’t understand my answer, I said, well, just let me stick in a factor of two or a factor of three—that’s what we did; that’s what Einstein did a long time ago. He couldn’t understand the expansion rate so he stuck in a fudge factor.

   You have the Big Bang and everything starts as a small point and things expand out. Well, as things expand out, there are the laws of gravity and mass begins to pull things back in, and so you should be able to measure the expansion rate accurately. But we don’t understand that. And so there’s a little blip at the very edge of the universe you can see. So the scale here is supposed to be our universe expanding out—there’s a little bit of a blip at the end that’s causing our universe to expand out a little bit and that’s the explanation for dark energy.

   It’s a huge mystery as to what is causing this, our universe, to expand out a bit more, and dark energy is only a phrase. It may not be dark and it may not be energy; it may be that we don’t understand something very fundamental about the universe. We said one simplistic idea for how to solve the dark energy issue is that we don’t understand the laws of gravity. Right? The reason we’re in this problem now is we believe we know there’s mass in the universe and that it expands and the mass interacts. Well, if that interaction is not what Newton or Einstein told us, we may have a problem. We know that the laws of gravity, according to Einstein, begin to break down on very high energies in very small scales. So why not, if the universe gets extremely big, in very large scales that it begins to break down again? It’s not such a stretch to think about that.

   So that’s one possibility. Another possibility is there is a new type of field, a new type of particle out there. I made up a cartoon sketch here of what’s in the universe. You see the proton, the neutron, a dark matter particle that we still don’t know what it is, and then a dark energy particle. These are just cartoon ideas of what it could be. And then I think the fundamental idea is what Einstein came up with a long time ago, that just the existence of space—it’s called the vacuum energy and it’s a cosmological constant—in just the existence of space itself there may be energy in space. Between both of us, between you and me, there is space. If there is somehow energy associated with that space, then what would happen as I walked away from you? I make more space; therefore, I make more energy. Therefore, if the universe gets really big, there’s a lot of space in the universe. Then the dark energy begins to take over and begins to accelerate the universe because the space has been made so big, the energy begins to dominate over everything else.

   We believe we’re in a state now that dark energy has won in the universe. It has beat the laws of gravity; it has beat the force of gravity. The gravitational force tries to pull things in and dark energy is pushing things out. So how we’re going to solve this is we’re going to use HETDEX, the Hobby-Eberly Telescope Dark Energy Experiment. So again, the fundamental problem here is that we have this thing called dark energy and the theorists—and I apologize Steve—have failed us.

   We don’t even know how to design an experiment to study this thing. We don’t know what it is and so we don’t know what to target. As an observer, I have to go back to the basics and think, “Okay, well, let’s just think about the observations.” The problem is the expansion rate of the universe; the only thing that we can do is to really nail down the expansion rate of the universe as well as we can. And so here what we do in HETDEX is we’re going to make a remarkable map of the universe and measure where the galaxies are.

   If you look at the top left, so that top left is a distribution of the galaxies in the universe when they were distributed early on in the universe; it was not a completely random distribution. They had a pattern in there. If you can map out that pattern over time, then you get the expansion rate. So we’re going to make a very detailed map of the universe and then trace it out as a function of time. That will tells us the expansion rate, and then we feed that back into the models of dark energy.

   I hope people have been out to McDonald Observatory; it’s a phenomenal place out there. The Hobby-Eberly Telescope is out there and it’s one of the biggest telescopes in the world. We’re going to chop off the top of the telescope and stick on a new instrument that can observe what we need. The problem of dark energy is enormous; you have to study enormous chunks of the sky in order to understand it, so we had to modify our telescope. Now, to modify a telescope that is on the frontier already where you have lots of scientists who are trying to use it and get fantastic data is difficult. And to say, “I’m going to chop this telescope apart and put on my instrument,” caused a little bit of a battle. But, thanks to my dean here, I think we’ve overcome that battle, so we’re going to build a fantastic instrument.

   So let me jump to a summary slide here. Dark energy is remarkably important and because of that, there are huge teams trying to understand this huge thing. Here I have a chart of these teams and HETDEX is the second line there. If you look at the column of institutions and you compare us to other places, you see that it’s the Department of Energy and it’s NASA. There are a few agencies here that represent pretty much all the countries in the world, and if you look at ours, it’s the only one we can actually point to as an institution. The University of Texas and Texas A&M team is often called the Texas Project.

   And so it really is Texas against the world in this, and we are relatively cheap, $34 million. That’s a lot of money, but in terms of the other dark energy experiments, we are relatively cheap. We are fast; we are going to start in 2010 and 2011 and we’ll go for three or four years. We are on schedule, on budget, and things look extremely good. And we are unique. We are looking at a chunk of the universe that none of the other experiments are looking at. We are looking at very early times in the universe and the other experiments are looking at the late times, at the times now, and the complement is what makes us extremely strong in that regard. The reason we can do this so well is because we own the telescope and we can do what we want to it.

   So just let me leave you with this: Science Magazine had their top 100 important mysteries in all of science and dark energy is number one. So if Science said it, it has to be important. Thank you for listening.

Discussion


Dr. Rankin: You’ve heard an array of presentations from lots of different perspectives. I didn’t anticipate how many different kinds of things we were going to hear this morning, so this is really exciting, lots of possibilities for discussion. I want to go back to the very beginning and just ask each of you to talk a little bit about what about discovery attracted you; what attracted you to this walk of life; what brought you into it?

Dr. Weinberg: In high school I read popular books about science, such as a book by James Jeans, The Mysterious Universe. I found in these books many things that I didn’t understand. I remember that there was an equation in the book that said q times p minus p times q equals i times h. I couldn’t understand this. I figured that q and p were symbols representing some numbers, but then how could q times p be any different from p times q? And if they were not different, then wouldn’t q times p minus p times q just equal zero, not something (whatever it was) called i times h? Eventually in college I found out. But back in high school I was led on by the attraction of mysterious, arcane, esoteric knowledge; knowledge that could only be gained through mathematics. I thought that understanding this sort of thing would be like knowing secrets that none of the kids on your block knew.

Dr. Cigarroa: Well, for me, Dean Rankin, it was the power of faculty members I was exposed to; I gave some examples. The individual who inspired me to always ask that other question was an individual by the name of Judah Folkman, a wonderful pediatric surgeon who made an observation that in the operating room tumors were  surrounded by blood vessels. He felt that he needed to take that observation to the lab and decide what that growth factor was that caused this new avascularization, and ultimately led to a new chapter in how you treat cancer.
S o again, for me it was really the power of an outstanding faculty member who stated that it’s not enough to be a physician; you have to ask the question why.

Dr. West: I think I would second the importance of a mentor and a role model, I didn’t grow up with scientists in my family or any scientists to be role models, Growing up, I didn’t know that this was a career path that even existed. It was the impact of individuals as I entered into the university system: Professor Robert Langer, I started working in his lab my freshman year in college, and Bob Langer, a renowned scientist who holds more patents than any other individual in the United States, spent time with a 17-year-old kid and help her along. I think that shows the importance of not just discovery, but how we impact the lives of the students who come through our systems.

Dr. Daniel: Well, as the engineer on the panel, I’m still trying to discover why I’m interested in the art of discovery, I guess it was problem-solving. As a young boy, I’d take my electric train apart and be highly motivated to figure out how to put it back together and penalized if I couldn’t. But I guess it’s always been an interest in problem-solving for me which usually means you have to discover something if you’re going to solve a nontrivial problem.

Dr. Gebhardt: I think that’s probably the same for me. I was always pretty good in math and so I didn’t know exactly what to do. I went to college and I wasn’t going to do astronomy or physics, but I took a course where we studied Steve Weinberg’s book, and I had no idea what he was talking about. I said, “I’ve got to try to figure this out,” and that did it.

Figure 3. Twins, one in need of liver transplant.