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Vol. LVIII, No. 15
July 28, 2006

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Finding the Evolution in Medicine

There is a reason we have four limbs rather than six like a centaur (head, arms and torso of a man attached to the body of a horse). There is a reason we compare our genes with those of numerous other animals, and why developing the yearly flu vaccine can be tricky. Explanations for these phenomena and other interesting facts were revealed in the Evolution in Medicine four-part lecture series held on campus recently. NIGMS and the Office of Science Education hosted the series, which was open to employees and the public.

Series planners say evolution is a timely subject for review. "Evolution unites the disciplines and is foundational to the research we do at NIH," said Dr. Irene Eckstrand, series coordinator and health scientist administrator at NIGMS.

Evolution and Development

Dr. Rudolf Raff discussed some of the misconceptions society has about evolution and highlighted research findings in evolutionary developmental (evo-devo) biology.  
Dr. Rudolf Raff is a professor at Indiana University and director of the Indiana Molecular Biology Institute. He is recog-nized as a pioneer in the field that merges evolutionary and developmental biology called "evo-devo," described in his book, The Shape of Life: Genes, Development, and the Evolution of Animal Form. Raff wants people to "understand that evolution is the underlying principal that organizes biology. Humans, their food and their pathogens are all products of evolution," he said.

Evo-devo scientists study body plans (actual body architecture) in plants and animals over developmental and geological time spans. Raff's research involves a pair of related Australian sea urchins (diverged 4 million years ago) that have similar body plans as adults but follow markedly different pathways to maturity. His data show that rapid morphological changes are linked to underlying genetic mechanisms such as the timing and regulation of expression of specific genes during early development.

Phylogenetic information — graphical representations of evolutionary relationships between organisms — is vital to evo-devo, said Raff. With it, you can learn about common ancestors, evolutionary trends in many biological processes and can make comparisons between divergent and related species. "In evolution, history matters. We have four limbs because our fish ancestors developed that way," he said.

Raff described some common misconceptions about evolution. Claims that there are no intermediates between major body plans in the fossil record are incorrect, he said. He cited some well-documented transitions such as those from fish to amphibian, dinosaur to bird and ape to human. We've all seen evolution presented as the sequential morphing of ape to human over time. Raff says this can be "effective, but misleading." He stressed that in reality, "evolution happens one generation at a time, during development."

Evolution and Education

Dr. Brian Alters is an international
leader in education and author of the best-selling book Defending Evolution in the Classroom.

Dr. Brian Alters is an international leader in education and the author of the best-selling book Defending Evolution in the Classroom. He holds dual appointments with McGill University in Montreal and Harvard University. He is also founder and director of the Evolution Education Research Center at McGill.

"Overall, the nation has a big problem," said Alters. "Approximately half of the U.S. population thinks evolution does (or did) not occur. While 99.9 percent of scientists accept evolution, 40 to 50 percent of college students do not accept evolution and believe it to be 'just' a theory," he reported.

Many university students have misconceptions about evolution that are amazingly ubiquitous, noted Alters. They believe that evolution is not pertinent to medical research or practice and has no relevance to AIDS, for example, or to antibiotic resistance in microbes.

Part of the problem is in effective teaching, he said. An instructional technique known as constructivism works best in the classroom, he suggested. Essential elements of constructivism include asking questions that require students to act based on what they think is accurate and presenting challenges so that misconceptions can be exposed and alternatives explored.

In the classroom, there is a tendency to separate science and religion as unique categories without overlap, Alters added. The separation results in an evolution-versus-creationism (or evolution-versus-intelligent design) struggle that is being waged in courtrooms and classrooms across the nation. "The key issue revolves around misunderstanding the nature of science, particularly that modern science does not entertain supernatural causation. Modern creationism involves the belief that a supernatural power intervened in the natural processes of the development of life on Earth. Proponents want this taught in science classrooms as science and oppose parts or all of biological evolution," he said.

Evolution and Genomics

Dr. Eric Green is scientific director of NHGRI and a distinguished scientist in the field of genomics. Genetics and genomics provide "a wealth of examples of how evolutionary principles can be used to gain a better fundamental understanding of basic biological processes and an understanding of the molecular underpinnings of human health and disease," he said.

"The Human Genome Project's name may be a misnomer," Green noted. From the outset, the project intended to make evolutionary compari-sons of other genomes, including those of the yeast, a fly, a worm and a mouse. The other species were chosen, in part, because "they were at distinct evolutionary time points, separated from humans roughly 80 million to 1,000 million years ago," he said. Evolutionary comparisons are illuminating details about the human genome and its function.

Evolutionary comparisons also aid in the study of genetic diseases. For many human diseases, there is a counterpart in animals. In some cases, the gene mutations responsible for a disease are identical and may occur in the same gene, Green explained.

"Our ability to interpret the human genome sequence is remarkably underdeveloped at this time," he admitted. Toward that end, an important goal is to identify all the sequence elements in the genome of functional importance, he said. They include sequences known to code for proteins as well as non-coding regions, sequences that do not code for proteins but still have a functional role. Establishing a catalog of functional sequences in the human genome will help efforts to identify the genetic changes that lead to complex genetic ailments such as diabetes and cardiovascular disease.

Green credited the work of Charles Darwin, described in The Origin of the Species, as laying the foundation for one of the most powerful tools available for interpreting the human genome sequence. Darwin wrote that it's not the strongest or most intelligent that survives, but "the one that is the most adaptable to change." Evolutionary changes that allow a species to adapt and survive now help scientists identify functional sequences in the genome. Nonfunctional sequences tend to undergo change more readily than functional areas, said Green.

Evolution and Infectious Diseases

Dr. Robin Bush is a professor of evolutionary biology at the University of California at Irvine. She collaborates with scientists at the Centers for Disease Control and Prevention using computational techniques and phylogenetic methods to study the evolution of influenza viruses.

Dr. Robin Bush, a professor of evolutionary biology at the University of California at Irvine, collaborates with scientists at the Centers for Disease Control and Prevention using computational techniques and phylogenetic methods to study the evolution of influenza viruses.  
Bush said the simplest type of phylogenetic tree has three taxa (divergent groups) that evolved from a common ancestor. "Think of it as a parent with three children," she explained. The length of the branches indicates genetic distance or the number of nucleotide changes that have occurred. A phylogenetic tree of the Orthomyxoviridae family of influenza viruses shows that strains A, B and C have all come from a common ancestor. All three infect humans. Strain A also infects pigs, horses and birds.

Her research focuses on the genes that code for surface proteins of the viral coat and how they evolve in response to the host's immune system. Hemagglutinin (HA) is needed for host receptor binding and host cell membrane fusion. Neuraminidase is needed for viral release from the host cell. There are a number of genetic variants for each of these proteins (H and N lead to such designations as H5N1). In humans, these proteins are constantly under attack by the immune system; in response, they have evolved very rapidly within humans, said Bush.

Bush uses phylogenetic trees to study changes in HA and to look for patterns between strains. She hopes to predict which strains may be responsible for the next year's flu and design more effective and better-targeted vaccines.

Videocasts of the lecture series can be found at and at

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