FOREWORD Creation and revelation: two different routes to advancement in the biomedical sciences Joseph L Goldstein This past summer, two of the world’s great art Tintoretto’s Paradiso in the Doge’s Palace in Entitled The 10-meter Tree, Penone’s tree is institutions—the Royal Academy of Arts in Venice. Hockney’s painting depicts an ordi- a single 10-meter timber beam that was cut in London and the Louvre in Paris—held exhi- nary English countryside in East Yorkshire half and presented in two parts, 16.5 feet high bitions in which the highlight was the depic- that most people would pass by without a each (Fig. 2). After removing the bark from the tion of a tree. Artists have long been fascinated second glance. In the background of the paint- two beams, Penone used a chainsaw and a chisel with trees, owing perhaps to the fact that trees ing, there’s a small thicket of trees, and in the to peel away the internal rings of growth. He are Nature’s only living elements that link the front there is one gigantic sycamore with its then meticulously worked around the knots to Heaven, the Earth and the Underworld. The immense, complex network of spreading and reveal the heart and soul of the tree: the inter- tree at the Royal Academy (a painting) and the intertwining branches. The painting is so nal structure of its narrow core and its develop- tree at the Louvre (a sculpture) exemplify two enormous that it literally engulfs the viewer in ing branches. The beams at each end were left different routes to achieving artistic greatness: a way that one feels like one is actually stand- untouched, signifying its status as a man-made one involving creation and the other involving ing in front of a real tree. object and providing natural pedestals for the revelation. Hockney painted Bigger Trees Near Warter in two side-by-side sculptures. When juxtaposed As in art, creation (through invention) and the outdoors in front of a live model of thicket against the voluptuous marble statuary in the revelation (through discovery) are two differ- and sycamore. His biggest hurdle in executing Cour Puget, Penone’s The 10-meter Tree is a ent routes to advancement in the biomedi- such a huge on-the-spot landscape was to over- work of great purity and spectacular elegance. cal sciences. The 2007 Lasker Clinical Award come the difficulty of stepping back to view According to Penone2, “the tree is an extraor- (awarded for the invention of prosthetic car- what he was doing in one part of the work in dinary sculpture capable of keeping within itself diac valves) is an example of advancement order to relate it to the rest of the painting. He the memory of its growth and of its evolution- through creation. The 2007 Lasker Basic Award solved this perspective problem by the use of ary and original form. I only reveal the form of (awarded for the discovery of the immune sys- an inventive tracking method that combined the matter. I give back its vitality.” In this sense, tem’s dendritic cells) exemplifies advancement digital photography with computer technol- Penone’s approach to sculpture harks back to through revelation. And the 2007 Lasker Public ogy. This approach allowed him to paint 50 Michelangelo’s concept, according to which the Service Award recognizes a life-long career identically sized smaller canvases that were sculptor does not create by adding matter to his devoted to both creativity and discovery. then assembled into the final mural. Once form, but reveals the form by removing mat- Hockney conceived his strategy, he and one ter that is already contained in the wood or the Creating a tree at the Royal Academy of assistant completed the painting in a three- stone. In much the same way that Michelangelo Arts week sprint—a tour de force of artistic inven- chiseled out and unveiled the statue of David The tree at the Royal Academy of Arts is the tion and creation. that preexisted in his block of Carrara marble, centerpiece of a painting by the Los Angeles– Penone discovered and revealed The 10-meter based British artist David Hockney. It was Revealing a tree at the Louvre Tree by taking matter away from his block of shown at the Academy’s annual Summer The tree at the Louvre is a sculpture by the Italian timber. This ‘revelation’ approach of removing Exhibition1, which has been in continual artist Giuseppe Penone—a leading protagonist matter is in striking contrast to the ‘creation’ existence since 1769. Entitled Bigger Trees of the Arte Povera movement of conceptual art, approach used by Hockney, who produced his Near Warter, Hockney’s painting is a mas- which focuses on elements derived from nature. tree from scratch by adding matter to his 50 sive mural, measuring 40 feet wide by 15 feet The Louvre invited Penone to select one of his canvases. high (Fig. 1). In size, it is a close second to the contemporary twentieth century sculptures that largest oil painting that has ever been made: would engage in a dialogue with the monumen- Lasker Clinical Award: creating prosthetic tal eighteenth century French garden statuary heart valves Published online 17 september 2007; doi:10.1038/ in the glass-enclosed Cour Puget courtyard of This year’s Clinical Award is awarded to the nm1642 the Richelieu wing of the Louvre. two surgeons who developed the first success- NATURE MEDICINE VOLUME 13 | NUMBER 10 | OCTOBER 2007 iii FOREWORD Figure 1 Bigger Trees Near Warter. 2007. Oil on 50 canvases, 15 × 40 feet overall. David Hockney’s creation of a tree fills a whole wall in the largest gallery at London’s Royal Academy of Arts. The man at the left with the walking cane is Hockney himself. The painting was on display at the Royal Academy’s Summer Exhibition in London, 11 June–19 August 2007. ful prosthetic mitral and aortic valves, which In addition to the Starr-Edwards valve, there coagulation therapy. Their one disadvantage is have prolonged and enhanced the lives of mil- are currently five other types of mechanical a shorter durability (about 15 years) versus the lions of patients with heart disease. The two heart valves used in patients today. Mechanical 30 to 40-year durability of mechanical valves. honored physicians are Albert Starr (Oregon valves are remarkably durable and long-lasting. Each year, more than 250,000 patients world- Health and Science University, Portland) and Their one disadvantage is a small risk of throm- wide receive a mechanical or a bioprosthetic Alain Carpentier (Hôpital Européen Georges- boembolism, requiring that valve recipients be porcine valve. In general, younger individu- Pompidou, Paris). permanently treated with oral anticoagulants. als receive mechanical valves, whereas older Until 1960, thousands of patients were hospi- This drawback stimulated intense interest in patients receive bioprosthetic valves. Both types talized every year with life-threatening conges- developing biological valves that would over- have benefited more than two million people tive heart failure, owing to severe abnormalities come the complication of thromboembolism. over the past 45 years. Their development is in their mitral and/or aortic valves caused by The first such tissue valves to be implanted a striking example of a biomedical advance congenital defects, rheumatic fever or age- were aortic homographs obtained from human achieved through the route of creation and related calcification and degeneration. The first cadavers. These homographs solved the prob- invention. successful creation and replacement of a heart lem of thromboembolism, but the limited valve in patients was accomplished in 1961 as availability of healthy human cadavers pre- Lasker Basic Award: revealing dendritic a result of a unique partnership between a 32- cluded their widespread use. cells year-old cardiac surgeon, Albert Starr, and a The breakthrough in biological valves came This year’s Basic Award is given to Ralph 60-year-old hydraulics engineer and inveterate in 1968 from the research of Alain Carpentier, Steinman (The Rockefeller University, New inventor, Lowell Edwards. a 35-year old cardiac surgeon in Paris, who pio- York), who discovered dendritic cells—a class Within two years of their first meeting, neered the use of tissue valves obtained from of immune cells that initiate and regulate the Starr and Edwards designed and developed pigs4. Pigs became the donor animal because body’s response to foreign antigens. a mechanical valve, tested it in dogs and then their hearts most closely resemble those of Antigen-presenting cells roam the body, implanted it into patients with rheumatic humans. The key to Carpentier’s success was sense foreign invaders such as bacteria and mitral stenosis—a tour de force of technical his insight of treating the porcine valves with viruses, ingest their antigenic proteins and invention and creation à la David Hockney. glutaraldehyde, a chemical that achieved two fragment them into short peptides. Each frag- The Starr-Edwards valve consisted of a functions: it strengthened the valve by cross- mented peptide then joins a major histocom- silicone-rubber ball encased in a Lucite cage3. linking cardiac tissue proteins, and it reduced patibility complex (MHC) molecule displayed The original design, with minor modifications, the immunogenicity of the heterograft. on the surface of the antigen-presenting cell. is still widely used today for aortic and mitral Carpentier coined the term ‘bioprosthetic The peptide-MHC complex is presented to replacements. Since 1962, more than 200,000 valve’ to denote its biological origin and its naive T lymphocytes, each of which expresses Starr-Edwards valves have been implanted prosthetic fate. a receptor molecule that enables it to recog- worldwide, and some of the original patients Compared to mechanical valves, bio- nize a different peptide-MHC combination.