HHMI's Holiday Lectures on Science

2012 Earth History/Climate Change Lecture 1

Mon, 29 Apr 2013 06:00:30 -0400

"The Deep History of a Living Planet" by Andrew Knoll, Ph.D.
The fossil record contains evidence of large animals only for the most recent 15 percent of Earth's history. Before then, life on our planet consisted primarily of microbes, which have left microfossil and chemical evidence of their existence. Microbes had a profound effect in shaping Earth's environment in the past. For example, when cyanobacteria evolved oxygen-generating photosynthesis, the event led to the oxygenation of the atmosphere and the evolution of eukaryotes and animals. Today many of Earth's ecosystems continue to depend on microbes. The same methods used to study the history of life on Earth are also being used to determine whether Mars ever supported life.

2012 Earth History/Climate Change Lecture 2

Mon, 29 Apr 2013 05:00:58 -0400

"Building Scientific Knowledge: The Story of Plate Tectonics" by Naomi Oreskes, Ph.D.
Accepting a scientific theory as scientific knowledge requires broad consensus among scientists. The theory of continental drift, which eventually became known as the theory of plate tectonics, was a remarkable synthesis of different lines of evidence. Yet, when first proposed in the 1920s by Alfred Wegener, the theory was rejected by many scientists. The story of how the theory eventually became accepted, many decades later, provides a fascinating glimpse into the process of building new scientific consensus.

2012 Earth History/Climate Change Lecture 3

Mon, 29 Apr 2013 04:00:33 -0400

"Earth's Climate: Back to the Future" by Daniel Schrag, Ph.D.
Changes in the atmospheric concentrations of greenhouse gases, such as carbon dioxide (CO₂), influence Earth's temperature. Geologic records show that Earth has been both much cooler and much warmer in the past compared to today, but this change in temperature was driven by a gradual rate of change in atmospheric CO₂ concentrations. The rate of modern day increases in CO₂ is unprecedented in human history and will have serious consequences in the near future and beyond, in terms of climate change, sea level rise, and species extinctions. Solutions to mitigate global warming are costly and challenging to implement.

2012 Earth History/Climate Change Lecture 4

Mon, 29 Apr 2013 03:00:33 -0400

"Climate Change: How Do We Know We're Not Wrong?" by Naomi Oreskes, Ph.D.
There is strong consensus among climate researchers that, based on careful analysis of the scientific evidence, human activities are causing climate change. Yet, the American public remains highly skeptical of this conclusion. Why? A look at this country’s history provides the answer. A Cold-War era think tank became an influential source of anti-regulation sentiment, swaying public opinion on many issues, from the harms of cigarette smoke to acid rain, and now, climate change.

2012 Earth History/Climate Change Discussion 1

Mon, 29 Apr 2013 02:00:33 -0400

"Climate Discussion" with Andrew Knoll, Ph.D., Daniel Schrag, Ph.D., and Sean Carroll, Ph.D.
The lecturers Andrew Knoll and Daniel Schrag discuss topics relating to climate change as they answer questions from students in the audience. Moderated by HHMI investigator and VP of Science Education, Sean Carroll.

2012 Earth History/Climate Change Discussion 2

Mon, 29 Apr 2013 01:00:33 -0400

"The Day the Mesozoic Died Short Film Discussion" with Andrew Knoll, Ph.D., Sean Carroll, Ph.D., Kirk Johnson, Ph.D., Tyler Lyson, Ph.D.
Students engage in a lively discussion about the film with Andrew Knoll of Harvard University; Sean Carroll, executive producer of the film; and two researchers featured in the film: Kirk Johnson, director of the National Museum of Natural History; and Tyler Lyson, postdoctoral researcher at the National Museum of Natural History.

2011 Human Evolution Lecture 1

Mon, 09 Apr 2012 06:00:40 -0400

"Human Evolution and the Nature of Science" by Tim D. White, Ph.D.
One of the most profound questions we can ask is "Where have we come from?" Charles Darwin addressed this question in his book on human evolution, The Descent of Man, which was published in 1871. Since then, scientists have gathered fossil and genetic evidence to give shape to the human evolutionary tree. Evolutionary science, like all science, involves processes for building a body of knowledge based on reason and evidence, and requires both creativity and critical thinking.

2011 Human Evolution Lecture 2

Mon, 09 Apr 2012 05:00:01 -0400

"Genetics of Human Origins and Adaptation" by Sarah A. Tishkoff, Ph.D.
The analysis of DNA sequences reveals the genetic heritage of modern humans. Using genetic evidence, scientists established that modern humans (Homo sapiens) originated from Africa. As groups of modern humans dispersed from Africa, they adapted to different environments around the globe. Genetic variations in human populations account for these adaptations, which continue to play a role in our lives. Examples of adaptations include what we choose to eat, what we are able to digest, and how susceptible we are to certain diseases.

2011 Human Evolution Lecture 3

Mon, 09 Apr 2012 04:00:18 -0400

"Stone Tools and the Evolution of Human Behavior" by John J. Shea, Ph.D.
Archaeology is the study of human residues using the scientific method to reconstruct human behavior. Residues are anything that results from human action, including stone tools. Tools are important in differentiating humans from other animals, and stone tools can be preserved over millions of years. By studying stone tools, scientists have learned how past human species might have lived and behaved, and how early humans differed from chimpanzees.

2011 Human Evolution Lecture 4

Mon, 09 Apr 2012 03:00:43 -0400

"Hominid Paleobiology" by Tim D. White, Ph.D.
In 1994, scientists discovered the remarkably well-preserved fossil of "Ardi," a member of the 4.4-million-year-old species Ardipithecus radius. Fossils found with Ardi indicate that she lived in a woodland rather than savanna habitat. Even more surprising than her ecology is the unique combination of humanlike and chimplike anatomical features. Ardi’s remains illuminate the divergent evolutionary histories of living chimpanzees and humans.

2011 Human Evolution Discussion 1

Mon, 09 Apr 2012 02:00:03 -0400

"Genetics of Bitter Taste Perception" with Sarah A. Tishkoff, Ph.D. and Michael C. Campbell, Ph.D.
Dr. Michael Campbell discusses how humans perceive the test of the chemical PTC. With Dr. Sarah Tishkoff, he fields questions about the evolution of taste perception, and scientific career choices.

2011 Human Evolution Discussion 2

Mon, 09 Apr 2012 01:00:08 -0400

"Reporting Scientific Results to the Public" with Charles Petit, John J. Shea, Ph.D., Ann Gibbons, Tim D. White, Ph.D., Sarah A. Tishkoff, Ph.D., Sean B. Carroll, Ph.D.
The lecturers and science reporters Ann Gibbons and Charles Petit discuss the particular challenges that arise when communicating scientific findings to the public.

2010 Infectious Diseases Lecture 1

Tue, 01 Mar 2011 07:00:02 -0500

"Dengue Fever: Breaking Epidemic Cycles" by Eva Harris, Ph.D.
Dengue fever is a rapidly re-emerging disease that has been spreading throughout Central America and is now being detected in the U.S. It is particularly devastating in tropical countries where healthcare resources are stretched thin. Dengue virus is spread by mosquitoes, and community-based efforts to control breeding mosquitoes have been effective.

2010 Infectious Diseases Lecture 2

Tue, 01 Mar 2011 06:00:18 -0500

"The Virus Hunter's Toolkit" by Joe DeRisi, Ph.D.
The first step in the battle against any infectious disease is to identify the infectious agent. Viruses can be identified based on their proteins or their genome. The Virochip is a DNA microarray diagnostic tool that can detect the genomes of known viruses as well as previously unknown varieties of viruses. Virochip technology is based on the basic molecular biology of DNA and RNA hybridization.

2010 Infectious Diseases Lecture 3

Tue, 01 Mar 2011 05:00:05 -0500

"Fighting Viruses in the Lab and Beyond" by Eva Harris, Ph.D.
Dengue virus comes in four subtypes. Fighting off a first dengue infection increases the risk for developing a more severe form of dengue fever if they are infected a second time with a different dengue virus subtype. Dengue virus leverages the immune system to its advantage. Enhancing developing countries’ scientific and clinical infrastructure can help the international effort to counter the spread of dengue.

2010 Infectious Diseases Lecture 4

Tue, 01 Mar 2011 04:00:05 -0500

"Solving SARS and Other Viral Mysteries" by Joe DeRisi, Ph.D.
The Virochip has been used to identify the infectious agents of SARS and other diseases. When the Virochip alone is not enough, new DNA sequencing technologies have been used to sequence all the nucleotides in the sample. Bioinformatic tools can then identify those sequences that are of viral origin. Recent advances in sequencing technology suggest that personal genome sequencing could become routine in the not too distant future.

2010 Infectious Diseases Discussion

Tue, 01 Mar 2011 03:00:44 -0500

"Biology of the Mosquito Vector" with Laura D. Kramer, Ph.D., Robin M. Moudy, Ph.D., and Eva Harris, Ph.D.
Mosquitoes are vectors for many viral diseases including dengue fever and West Nile. Understanding how a virus infects the mosquito is important in understanding how the disease will spread. On Grand Cayman, transgenic mosquitoes have been used in an effort to eradicate the mosquito vector. This discussion explores the ethics of genetically-modified organisms and other topics.

2009 Biodiversity Lecture 1

Mon, 08 Mar 2010 07:00:00 -0500

"From Venoms to Drugs" by Baldomero M. Olivera, Ph.D.
Natural selection has produced an astounding array of venoms for prey capture. Marine cone snails are among the most dangerous venomous creatures. Cone snail venoms are potent, deadly to fish and people, and each species makes a venomous cocktail of up to 200 different toxins. One of these toxins has been developed into a drug called Prialt--a pain killer that prevents the spinal cord from relaying pain information to the brain. With over 700 living species of cone snails, each having up to 200 unique toxins, there are potentially more than 140,000 novel molecules with drug potential.

2009 Biodiversity Lecture 2

Mon, 08 Mar 2010 06:00:00 -0500

"Shedding Light on an Invisible World" by Bonnie L. Bassler, Ph.D.
Bacteria live in and on us in complex communities that outnumber the cells and genes of our own tissues. These bacteria possess a communication mechanism that allows them to coordinate their activities. This mechanism, called quorum sensing, was first described in bacteria living symbiotically in a squid. The bacteria produce bioluminescence which simulates moonlight and camouflages the squid. The key to quorum sensing is a molecular signal released by the bacteria that is monitored by receptors, which in turn modulate gene expression. Bioluminescence genes are only turned on when the population density--and therefore the signal concentration--is high.

2009 Biodiversity Lecture 3

Mon, 08 Mar 2010 05:00:00 -0500

"Biodiversity at a Snail's Pace" by Baldomero M. Olivera, Ph.D.
Cone snail venoms have a wide variety of effects, ranging from convulsive shock, to paralysis, to sedation. The venoms contain a mixture of peptide toxins that simultaneously attack different molecular targets of the nervous system. The evolution of such a diversity of toxins is made possible by multiple gene superfamilies containing hypervariable sequences. The research and medical value of a group of animals like the cone snails is a powerful reminder of what we can learn from biodiversity. Venomous relatives of the cone snails--the turrid snails--number over 10,000 known species, representing a million compounds of potential pharmacological value.

2009 Biodiversity Lecture 4

Mon, 08 Mar 2010 04:00:00 -0500

"Eavesdropping on Tiny Conspiracies" by Bonnie L. Bassler, Ph.D.
Pathogenic bacteria use quorum sensing to launch a simultaneous attack when in sufficient numbers. Bacteria possess at least two systems of quorum sensing. They sense their own species' numbers by monitoring their species-specific quorum sensing signal. Bacteria also sense a signal that is shared between different species to obtain information about the bacterial community. Manipulating quorum sensing is a promising approach for developing new antibiotics against pathogens, or probiotics for industrial applications.

2009 Biodiversity Discussion 1

Mon, 08 Mar 2010 03:00:00 -0500

"Biodiversity Discussion" with E.O. Wilson & Eric Chivian
Questions on biodiversity, endangered habitats, and how best to preserve the Earth's ecosystems, are answered by Dr. E.O. Wilson of the Department of Organismic and Evolutionary Biology at Harvard University, Dr. Eric Chivian of the Center for Health and the Global Environment at Harvard Medical School, Dr. Bassler and Dr. Olivera. Drs. Wilson and Chivian deliver short presentations on biodiversity to start the session. The question and answer session is moderated by HHMI President Dr. Robert Tjian.

2009 Biodiversity Discussion 2

Mon, 08 Mar 2010 02:00:00 -0500

"Q&A on Quorum Sensing" with Bonnie L. Bassler, Ph.D.
Dr. Bonnie Bassler discusses antibiotics development, quorum sensing, and other topics related to bacteria in a question-and-answer session with a student audience.

2009 Biodiversity Discussion 3

Mon, 08 Mar 2010 01:00:00 -0500

"Q&A on Cone Snails" with Baldomero M. Olivera, Ph.D.
Dr. Baldomero Olivera discusses various aspects of the biology of the venomous cone snails in a question-and-answer session with a student audience.

2008 Neuroscience Lecture 1

Wed, 01 Apr 2009 05:00:00 -0400

"Mapping Memory in the Brain" by Eric R. Kandel, M.D.
What is mind? A central finding is that mind is a series of processes carried out by the brain. Mind is to the brain as walking is to legs—but it is infinitely more complex. The brain produces our every emotional, intellectual, and athletic act. It allows us to acquire new facts and skills and to remember them for as long as a lifetime.

Mind emerges from brain activity, and specific mental functions are localized to different regions in the brain. Over the past few decades, we have found that memory exists in two major forms, each located in different brain regions. Explicit memory is for people, places, and objects. During the memorization process it requires a region deep in the brain called the hippocampus. We depend on our hippocampus to remember our first day in high school. In contrast, implicit memory serves perceptual and motor skills, such as dancing and swimming. It is distributed over multiple brain regions and circuits. In concert, these two memory systems help make us who we are.

2008 Neuroscience Lecture 2

Wed, 01 Apr 2009 04:00:00 -0400

"Building Brains: The Molecular Logic of Neural Circuits" by Thomas M. Jessell, Ph.D.
The human brain is the sophisticated product of 500 million years of vertebrate evolution, assembled during just nine months of embryonic development. The functions encoded by its trillion nerve cells direct all human behavior—from the simple movements of everyday life to the daring and inspirational thoughts that sometimes emerge. Yet the brain is a biological organ made from the same building blocks as skin, liver, and lung. How does the brain acquire its remarkable computational power? Answers lie in the details of its construction—the cellular and molecular mechanisms that drive the formation of thousands of neural circuits, each wired for a specific behavior. We'll delve into the developmental programs that control brain wiring to understand the cues that trigger neurons to take the correct shape and connect with appropriate partners. As the genetic blueprint for brain wiring unfolds, early experience validates neural networks by frequent use, sculpting the final pattern of neural connections and thus enabling and constraining our behavior. We'll also explore how understanding neural circuit assembly suggests ways of treating the many neurological and psychiatric disorders that result from mistakes in brain wiring.

2008 Neuroscience Lecture 3

Wed, 01 Apr 2009 03:00:00 -0400

"Plan of Action: How the Spinal Cord Controls Movement" by Thomas M. Jessell, Ph.D.
Behavior involves movement. Movement drives simple respiratory programs to keep us breathing, as well as displays of emotion—desire, joy, remorse—that project our inner thoughts and moods. Understanding the workings of the neural circuits that control movement gives us a glimpse of how brain wiring and circuit activity control specific behaviors, including one of the more sophisticated aspects of human motor behavior—the movement of our limbs. Consider baseball player Lou Gehrig's remarkable hand-eye coordination as he compiled one of baseball's most impressive hitting streaks, or the purity of cellist Jacqueline du Pré's tone as she played Haydn's Cello Concerto. Yet, both examples also remind us of the fragility of the motor system and its vulnerability to diseases: Gehrig succumbed to amyotrophic lateral sclerosis and du Pré to multiple sclerosis. Neural circuits in the spinal cord direct motor programs with impressive precision, ensuring that the many muscles in a limb are activated in precise temporal order. Sensory feedback systems report on the accuracy of motor programs, and signals from the brain permit us to change motor strategies moment by moment to accommodate an ever-changing world.

2008 Neuroscience Lecture 4

Wed, 01 Apr 2009 02:00:00 -0400

"Memories are Made of This" by Eric R. Kandel, M.D.
Do the brain's two major memory systems—implicit and explicit—have any common features? Can molecular biology, which has enhanced understanding of many other bodily functions, help us understand mental function?

Implicit and explicit memory both have a short-term component lasting minutes (for example, remembering the telephone number you just looked up) and a long-term component that lasts days, weeks, or a lifetime (for example, remembering your mother's birthday). For both memory processes, the conversion from short- to long-term memory generally requires repetition. And in both, long-term memory requires the synthesis of new proteins. Short-term memory is mediated by modifications of existing proteins, leading to temporary changes in the strength of communication between nerve cells. In contrast, long-term memory involves alterations of gene expression, synthesis of new proteins, and growth of new synaptic connections. It is the growth of synaptic connections—they may be forming in your brain as you read this—that produces enduring long-term memory. Insights into the molecular biology of memory storage have led to an improved understanding of memory disorders produced by brain diseases—and the promise of improved treatments.

2008 Neuroscience Discussion

Wed, 01 Apr 2009 01:00:00 -0400

"Neurobiology and Mental Illness"
Dr. Kay Jamison of the Johns Hopkins University School of Medicine, and Dr. Gerald Fischbach of the Simons Foundation, join Drs. Kandel and Jessell to address student comments and questions concerning autism, manic depression, and other mental illnesses.

2007 HIV/AIDS Lecture 1

Tue, 01 Apr 2008 06:00:00 -0400

"From Outbreak to Epidemic" by Bisola O. Ojikutu, M.D., M.P.H.
In 1981, an obscure and deadly disease surfaced. Previously healthy homosexual men in the United States began arriving at clinics with rare cancers and infections usually seen in people with weakened immune systems. Most of them died. The medical community was baffled and the public anxious. As the cases multiplied, so did the questions. Who is at risk? What is causing the disease? Why does it lead to failure of the immune system? And most important: Can it be stopped from spreading? The new disease was named acquired immune deficiency syndrome, or AIDS, and it has now killed more than 25 million people worldwide. After the initial outbreak, different sectors of the public health, medical, scientific, and advocacy communities mobilized in response to the deadly epidemic. They focused on surveillance—that is, detecting and mapping the disease—and prevention.

2007 HIV/AIDS Lecture 2

Tue, 01 Apr 2008 05:00:00 -0400

"AIDS and the HIV Life Cycle" by Bruce D. Walker, M.D.
The first AIDS cases—otherwise healthy young men with multiple infections and cancers—were a mystery to even the most seasoned physicians. The symptoms pointed to a major defect in the immune system. Further investigation found swollen lymph nodes, another sign of immune stress. A clear hypothesis emerged: the cells of the immune system were directly infected. Tissue cultured from patients' lymph nodes revealed a new virus—a retrovirus. This type of virus contains RNA that it converts to DNA once it infects human cells. Named human immunodeficiency virus, or HIV, its viral code integrates into the host genome, a safe haven from most drugs, and causes lifelong infection. HIV infects lymphocytes throughout the body, disabling the very cells that defend against invading viruses. With a weakened immune system, patients are vulnerable to infections that are normally easy to fend off. A detailed understanding of the HIV life cycle, from cell attachment and entry to translation and assembly of new viruses, can help researchers identify targets for drug therapy.

2007 HIV/AIDS Lecture 3

Tue, 01 Apr 2008 04:00:00 -0400

"Drugs and HIV Evolution" by Bisola O. Ojikutu, M.D., M.P.H.
In 1987, four years after HIV was identified, the Food and Drug Administration (FDA) approved the use of azidothymidine (AZT) to slow the progression of HIV infection to full-blown AIDS. AZT targets reverse transcriptase, an enzyme essential to HIV replication in lymphocytes. Unfortunately, HIV evolves rapidly and develops resistance to AZT, making single-drug therapy with reverse transcriptase inhibitors ineffective. In 1996, a new class of antiretroviral drugs, called protease inhibitors, was approved. This development led to a treatment strategy called highly active antiretroviral therapy (HAART), a drug "cocktail" combining multiple drugs that target at least two steps in the HIV life cycle. As a result, deaths from AIDS in developed nations have dropped significantly, making HIV a chronic, treatable disease, not a death sentence. Since 1987, more than 20 drugs have been approved for use in combination to treat HIV infection, and more are in the pipeline. New drug classes include chemical agents that inhibit the virus's entry into the cell, integration into the host genome, and maturation.

2007 HIV/AIDS Lecture 4

Tue, 01 Apr 2008 03:00:00 -0400

"Vaccines and HIV Evolution" by Bruce D. Walker, M.D.
The global HIV epidemic continues to spread: 40 million people are infected worldwide. While drugs are essential in the battle against HIV, a vaccine would be a major advance. A vaccine, for example, can be preventive and does not require frequent dosing. HIV's ability to evolve rapidly is a major hurdle in developing a vaccine. HIV replication uses a reverse transcriptase enzyme that converts viral RNA into DNA. The enzyme is poor at reading and correcting mistakes. With successive replication cycles, alterations in viral genes accumulate, resulting in the evolution of new viral traits. HIV shows more variability in a single person than the total viral variability seen across a global influenza epidemic. This rapid HIV evolution makes it difficult to pick a stable protein sequence to target for vaccine development. Currently, the focus is on keeping HIV in check rather than developing a completely preventive vaccine. Individuals whose native immunity has kept HIV under control for more than 25 years may provide clues for creating a vaccine.

2007 HIV/AIDS Discussion 1

Tue, 01 Apr 2008 02:00:00 -0400

"Students fighting the HIV epidemic"
A 90-minute discussion session with the lecturers, Washington, D.C.-area high school students, and three students—Piali Mukhopadhyay, Shefali Oza, and Stella Safo—who are helping in the global fight against HIV and AIDS.

2007 HIV/AIDS Discussion 2

Tue, 01 Apr 2008 01:00:00 -0400

"Living with HIV"
A 90-minute discussion session with the lecturers, Washington, D.C.-area high school students, and three HIV-positive individuals—Adam Barrett, Zinhle Thabethe, and Phill Wilson—who share their personal experiences about living with HIV.

2000 Biological Clocks Lecture 1

Tue, 04 Sep 2007 04:00:00 -0400

"Biology in Four Dimensions" by Joseph S. Takahashi, Ph.D.
After describing the fundamental properties of circadian rhythms, Dr. Takahashi takes us on an exciting journey into a very special region of the brain—the suprachiasmatic nucleus (SCN). The SCN functions as a "master" biological clock that governs our physiology and certain behaviors. The clock regulates rhythms of sleep and wakefulness that make us morning larks, evening owls, or something in between. When the master clock is out of synchrony with other biological clocks in the body, symptoms of jet lag ensue.

2000 Biological Clocks Lecture 2

Tue, 04 Sep 2007 03:00:00 -0400

"Unwinding Clock Genetics" by Michael Rosbash, Ph.D.
Dr. Rosbash reveals that the fruit fly (Drosophila melanogaster) has a biological clock in its nervous system. Although tiny in size, the fruit fly has had a major impact on our understanding of circadian rhythms. The fruit fly served as the instrument with which scientists proved that certain behaviors such as rest and activity are under direct genetic control. Although much remains to be learned, the outlines of how the biological clock functions have emerged from research on this singular insect.

2000 Biological Clocks Lecture 3

Tue, 04 Sep 2007 02:00:00 -0400

"PERfect TIMing" by Michael Rosbash, Ph.D.
Dr. Rosbash discloses how scientists have persuaded Mother Nature to reveal the inner workings of the fruit fly's biological clock. From the almost 14,000 genes in this organism, scientists have painstakingly identified a handful that regulate the "ticktock" of the biological clock. In doing so, scientists have also brilliantly shown how the environment resets our biological clocks so that they are in synchrony with the cycles of nature.

2000 Biological Clocks Lecture 4

Tue, 04 Sep 2007 01:00:00 -0400

"The Mammalian Timekeeper" by Joseph S. Takahashi, Ph.D.
Dr. Takahashi describes the powerful strategies that he and others have harnessed for understanding biological clocks in mammals. To tease out the secrets of how the clocks in higher organisms function, scientists had to overcome uncommonly high hurdles posed by the complexity of mice, hamsters, and humans. Many of these studies used the increasingly important research tools of genomics and computer-based informatics. One payoff already is a better understanding of human sleep disorders that are linked to specific genes.

2001 Sex Determination Lecture 1

Wed, 01 Aug 2007 04:00:00 -0400

"Deciphering the Language of Sex" by David C. Page, M.D.
Is it a boy or a girl? Dr. Page looks at how we define male and female and summarizes the development of human sex characteristics. He then explains the role of the sex chromosomes, X and Y, and, in particular, the SRY gene. Dr. Page demonstrates the differences between species that reproduce sexually and those that reproduce clonally without sex. A likely major advantage of sexual reproduction is that meiotic recombination and subsequent natural selection can weed out deleterious mutations.

2001 Sex Determination Lecture 2

Wed, 01 Aug 2007 03:00:00 -0400

"Hermaphrodites: The Safer Sex" by Barbara J. Meyer, Ph.D.
Dr. Meyer explains the value of studying model organisms and introduces the nematode C. elegans Affectionally known as "the worm," it has two sexes: male, which possesses a single X chromosome, and hermaphrodite, which possesses two X chromosomes. Dr. Meyer explains that sex determination is controlled by the xol-1 gene. Xol-1 gene expression is regulated by sex-determining factors produced by the X chromosome.

2001 Sex Determination Lecture 3

Wed, 01 Aug 2007 02:00:00 -0400

"Sex and Death: Too Much of a Good Thing" by Barbara J. Meyer, Ph.D.
Having too many chromosomes can lead to too much gene expression. If a male and a female have a different number of X chromosomes, a dosage-compensation mechanism is necessary to equalize the level of gene expression. In human females who have two X chromosomes, one X chromosome in each cell is inactive, while in C. elegans hermaphrodites, the activity of both X chromosomes is reduced by half. Dr. Meyer explains how the gene that controls dosage compensation in C. elegans works. Some genes involved in dosage compensation also have a role in cell division.

2001 Sex Determination Lecture 4

Wed, 01 Aug 2007 01:00:00 -0400

"Sexual Evolution: From X to Y" by David C. Page, M.D.
Dr. Page interprets the results of an audience-participation experiment comparing testosterone levels in males and females of varying ages. He then explains how the Y chromosome is inherited from father to son in a near clonal fashion. He demonstrates that successive inversions and deletions during mammalian evolution have reduced the Y chromosome to its present form—small and sparsely populated with genes. In some men, a deletion in the Y chromosome can lead to infertility. Dr. Page describes how intracytoplasmic sperm injection can help these men father children.

1995 RNA Lecture 1

Mon, 02 Jul 2007 04:00:00 -0400

"Catalysis, Chemical and Biochemical" by Thomas R. Cech, Ph.D.
Life processes are fundamentally chemical reactions. Left to themselves, however, the reactions would occur too slowly and nonspecifically to sustain life. Cellular enzymes are catalysts that tame reactions by accelerating them, lending specificity, and regulating their time and place. Some principles of biological catalysis are demonstrated.

1995 RNA Lecture 2

Mon, 02 Jul 2007 03:00:00 -0400

"RNA as an Enzyme: Discovery, Origins of Life, and Medical Possibilities" by Thomas R. Cech, Ph.D.
Discovery of RNA's catalytic activity led to unexpected spin-offs, including a new scenario for the origin of life. In a different area, the ability of RNA catalysts (ribozymes) to cut and splice RNA molecules has sparked efforts to develop them as pharmaceuticals against viruses, cancer, and genetic diseases.

1995 RNA Lecture 3

Mon, 02 Jul 2007 02:00:00 -0400

"How to Accelerate a Reaction 100,000,000,000 Times Using Only RNA" by Thomas R. Cech, Ph.D.
RNA and protein are built from different chemical units and assembled in distinct ways. Thus, the ability of RNA to exhibit catalytic activity rivaling that of traditional protein enzymes was unexpected. Studies of RNA catalytic centers have revealed much about their structure and mode of action.

1995 RNA Lecture 4

Mon, 02 Jul 2007 01:00:00 -0400

"Life at the End of the Chromosome: Another RNA Machine" by Thomas R. Cech, Ph.D.
Chromosomes of humans and other eukaryotes contain linear DNA molecules. The chromosome ends, or telomeres, are necessary for DNA stability and replication. Telomere replication is carried out by telomerase, whose RNA subunit acts as a template for telomeric DNA synthesis.

1999 Infectious Diseases Lecture 1

Mon, 04 Jun 2007 05:00:00 -0400

"Microbe Hunters: Tracking Infectious Agents" by Donald E. Ganem, M.D.
How are diseases recognized as infectious and how are their causes identified? In this lecture, Dr. Ganem describes how epidemiologists, physicians, and microbiologists work together to identify and study pathogens. He first explains what viruses are and how they reproduce and infect cells. Dr. Ganem then elucidates the increasingly important role of DNA-based techniques in identifying infectious agents by telling how he and other scientists uncovered a virus strongly implicated in causing Kaposi's sarcoma--the leading cancer that affects AIDS patients.

1999 Infectious Diseases Lecture 2

Mon, 04 Jun 2007 04:00:00 -0400

"The Microbes Strike Back" by B. Brett Finlay, Ph.D.
Dr. Brett Finlay explains why bacterial diseases continue to be a major health problem worldwide, causing a third of the world's deaths every year. After describing how bacteria grow, reproduce, and spread, Dr. Finlay explains how antibiotics work--and why they are not always successful in stopping infection. He describes the "genetic Internet" that enables certain pathogenic bacteria or "superbugs" to "download" genes that are resistant to all available antibiotics. He also explains how vaccines--an important tool in fighting infectious diseases--are developed. Dr. Finlay concludes his talk with a look at the potential uses of pathogenomics (the genomics of bateria) in fighting infection.

1999 Infectious Diseases Lecture 3

Mon, 04 Jun 2007 03:00:00 -0400

"Outwitting Bacteria's Wily Ways" by B. Brett Finlay, Ph.D.
With bacteria invading our best weapons, where do we begin to search for new weapons? Dr. Finlay showcases three types of bacteria--E. coli, Salmonella, and Listeria--to illustrate how molecular biology is allowing researchers to probe the molecular workings of bacterial infections. He describes how these pathogens use their genetic "toolkits" of virulence factors to cause disease. These factors, as diverse as the hosts they invade, can be transferred between different bacteria by genetic exchange, giving rise to new bacterial pathogens and diseases. Dr. Finlay discusses how an understanding of the role of virulence factors is causing disease can lead to potential new therapies for treatment and prevention.

1999 Infectious Diseases Lecture 4

Mon, 04 Jun 2007 02:00:00 -0400

"Emerging Infections: How Epidemics Arise" by Donald E. Ganem, M.D.
Dr. Ganem analyses the complex causes of epidemics. He explains how both genetic mutations and changes in the environment and in human social behavior can give rise to new infectious diseases by upsetting a previously established balance between a pathogen and its natural host. He discusses how genetic changes in the structure of the influenza virus have led to epidemics and pandemics. Dr Ganem also shows the impact of weather on a 1993 outbreak of hantavirus, describes the effect of human migratory patterns on the spread of smallpox, and examines what happened when the myxoma virus was introduced in Australia in the 1950s to control the rabbit population.

2003 Cancer Lecture 1

Mon, 07 May 2007 17:00:00 -0400

"Research Mechanics: Putting the Brakes on Cancer" by Bert Vogelstein, M.D.
Cancers are caused by an accumulation of mutations that alter the activity of genes involved in controlling cell birth, growth, and death. Some of these errors are inherited. Most, however, occur after birth, triggered by cancer-causing agents in the environment or by mistakes that happen when cells divide. If the growth of cancer can be likened to a car speeding out of control, the mutations that cause the disease are the functional equivalent of cutting the brakes, gluing down the accelerator, or hiring an inept mechanic—or doing all three at once. Dr. Vogelstein explains that although there are numerous kinds of cancer, all stem from alterations that allow cell division to outstrip cell demise.

2003 Cancer Lecture 2

Mon, 07 May 2007 16:00:00 -0400

"Chaos to Cure: Bringing Basic Research to Patients" by Bert Vogelstein, M.D.
The identification of hundreds of genes involved in the formation and spread of cancer is leading to promising new methods for diagnosis, prevention, and treatment. In the case of colon cancer, researchers are developing genetic tests for detecting the cancer-causing mutations. Researchers are also investigating anticancer therapies that take advantage of the molecular differences between cancer cells and the normal cells surrounding them. Gleevec, for example, is a compound designed to disable a protein that spurs the growth of certain types of leukemia. In Dr. Vogelstein's lab, scientists are deploying specialized microbes to penetrate tumors, proliferate rapidly, and kill the cancer cells.

2003 Neuroscience Lecture 3

Mon, 07 May 2007 15:00:00 -0400

"A Healthy Nervous System: A Delicate Balance" by Huda Y. Zoghbi, M.D.
Mutations in key genes can lay waste to the nervous system. Spinocerebellar ataxia type 1 (SCA1), for example, can start with a stagger at age 30 or 40. Patients eventually experience severe muscle deterioration, rendering them unable to talk, swallow, or even breathe. By studying large families predisposed to developing SCA1, Dr. Zoghbi and her colleagues identified the responsible altered gene. The culprit is a sort of genetic stutter that increases the size of the SCA1 gene. As a result, the product of the mutant gene—a protein called ataxin-1—forms large, sticky clumps that disable the neurons involved in controlling movement. Dr. Zoghbi is now searching for compounds that will clear ataxin-1 tangles.

2003 Neuroscience Lecture 4

Mon, 07 May 2007 14:00:00 -0400

"The Strength of Families: Solving Rett Syndrome" by Huda Y. Zoghbi, M.D.
Girls with Rett syndrome develop normally for about 18 months and then begin to regress. Eventually, they have difficulty walking, speaking, and even using their hands. With the help of affected girls and their families, Dr. Zoghbi and her collaborators searched for the gene responsible for this neurological disorder. After 16 years, they found the gene, called MECP2, on the X chromosome. It encodes a protein essential to the normal functioning of nerve cells in the brain. Mutations in the gene disrupt the activity of neurons early in life, when they are forming critical connections. Dr. Zoghbi discusses how identification of this gene should lead to better methods for diagnosing and treating Rett syndrome.

2003 Cancer/Neuroscience Bioethics Discussion

Mon, 07 May 2007 13:00:00 -0400

Bioethics Discussion
Genetic research benefits health, but also raises thorny ethical issues. View a discussion among high school students, moderated by Huda Zoghbi and Bert Volgelstein, and ethicist Laurie Zoloth.

2002 Genomics & Chemical Genetics Lecture 1

Mon, 02 Apr 2007 17:00:00 -0400

"Reading Genes and Genomes" by Eric S. Lander, Ph.D.
The 20th century opened with the rediscovery of Gregor Mendel's work on inheritance. By the close of the century, the human genome was almost fully sequenced. Dr. Lander takes us on a tour of this remarkable genetic century, demonstrating how rapid advances in DNA sequencing technologies and information science have been essential in accelerating the pace of whole-genome sequencing of different organisms. He also discusses the total number of human genes and other features of the human genome. A comparison of the human genome with the recently completed mouse genome reveals remarkable similarities, as well as some important evolutionary differences.

2002 Genomics & Chemical Genetics Lecture 2

Mon, 02 Apr 2007 16:00:00 -0400

"Probing Genes and Genomes" by Stuart L. Schreiber, Ph.D.
To understand life's processes, perturb them. How a process responds to an insult can provide clues about normal function or mimic a specific disease state. Gene mutation is one powerful perturbation method. Dr. Schreiber discusses a newer approach, called chemical genetics, that uses small molecules to bypass genes and perturb proteins directly. He illustrates the approach with the small molecule furrowstatin, which interrupts the process of cell division. Dr. Schreiber also explains diversity-oriented synthesis, a process that can rapidly create thousands of different molecules. He discusses the molecular screening methods needed to identify which of thousands of molecules may be useful for understanding a protein's function—or even for developing a new medicine.

2002 Genomics & Chemical Genetics Lecture 3

Mon, 02 Apr 2007 15:00:00 -0400

"Human Genomics: A New Guide for Medicine" by Eric S. Lander, Ph.D.
With the exception of identical twins, no two human genomes are exactly the same. But how different are they? Are two humans more alike than two orangutans? Dr. Lander explores human genetic variation and how it may affect individual susceptibility to certain diseases. A collaborative research effort is now cataloging all common human genetic variations to help us better understand disease mechanisms. Dr. Lander also discusses a powerful tool—the DNA microarray—that can be used to measure the expression level of many genes simultaneously. DNA microarrays, for example, have been helpful in diagnosing different tumors. The widespread use of microarray technology promises to guide research into specific genes and proteins associated with many diseases.

2002 Genomics & Chemical Genetics Lecture 4

Mon, 02 Apr 2007 14:00:00 -0400

"Chemical Genomics: New Tools for Medicine" by Stuart L. Schreiber, Ph.D.
Scientists now have the ability to create millions of new molecules. How do they test whether any of these molecules are useful? Focusing on a network of proteins involved in glucose sensing and type II diabetes, Dr. Schreiber explains two methods for screening small molecules. Small-molecule microarrays are used to screen for molecules that bind to specific proteins. In cell-based screening, proteins can be probed while performing their cellular jobs. Robotic automation and inexpensive computing have made these mass-scale parallel assays practical. Dr. Schreiber also discusses ChemBank, a project designed to gather information linking proteins, small molecules, and functions. He suggests that in the future, a synergy of chemistry, biology, and computational science may help scientists classify a host of small molecules that affect specific biological functions.

2002 Genomics & Chemical Genetics Teacher Discussion Session

Mon, 02 Apr 2007 13:00:00 -0400

Teacher Discussion Session
A wide-ranging 45-minute discussion between Dr. Eric Lander, Dr. Stuart Schreiber, and four Washington DC-area high school teachers, who ask the lecturers about how they became involved in science, the increasing importance of genomics in biological research, and the role of science in the classroom. Moderated by Dr. Thomas Cech, president of the Howard Hughes Medical Institute.

2006 Stem Cells Lecture 1

Tue, 06 Mar 2007 17:00:00 -0500

"Understanding Embryonic Stem Cells" by Douglas A. Melton, Ph.D.
During embryonic development, stem cells generate all the specialized cells that populate body tissues such as muscle, the nervous system, and blood. The term embryonic stem cells, or ES cells, is used by researchers for cells that can be isolated from early embryos, before they differentiate into specific types of cells. Depending on when they are isolated, embryonic stem cells are pluripotent-able to become virtually any type of cell—or multipotent—able to become many, but not all, types of cells. Because stem cells have the potential to generate fresh, healthy cells of nearly any type, there is interest in exploring their use to treat and cure various diseases. The societal controversy regarding human ES cells relates primarily to their derivation from very early embryos. In addition, certain stem cell lines are developed using a cloning technique called somatic cell nuclear transfer, which can generate cells that are an exact genetic match to a patient.

2006 Stem Cells Lecture 2

Tue, 06 Mar 2007 16:00:00 -0500

"Adult Stem Cells and Regeneration" by Nadia Rosenthal, Ph.D.
Mature organisms have stem cells of various sorts, called adult stem cells. Adult stem cells supply cells that compensate for the loss of cells from normal cell death and turnover, such as the ever-dying cells of our skin, our blood, and the lining of our gut. They are also an essential source of cells for healing and regeneration in response to injury. Some animals, such as sea stars, newts, and flatworms, are capable of dramatic feats of regeneration, producing replacement limbs, eyes, or most of a body. It is an evolutionary puzzle why mammals have more limited powers of regeneration.

Researchers are interested in pinpointing where adult stem cells reside and in understanding how flexible adult stem cells are in their ability to produce divergent cells such as muscle and red blood cells. Understanding the sources and the rules for the differentiation of adult stem cells is essential for tapping their therapeutic potential. Since consenting adults can provide adult stem cells, some people think that adult stem cells may be a less controversial area of research than embryonic stem cells.

2006 Stem Cells Lecture 3

Tue, 06 Mar 2007 15:00:00 -0500

"Coaxing Embryonic Stem Cells" by Douglas A. Melton, Ph.D.
There are two main approaches to using stem cells to fight human diseases: develop stem cells to produce therapeutic replacement cells and study stem cells as a model for understanding the biology of a disease. Significant progress has been made in producing stem cell lines that, for example, participate in the regeneration of damaged nervous tissue. Many human diseases, such as juvenile diabetes (type 1 diabetes), involve malfunctioning genes and environmental triggers. Usually, a specific type of cell is primarily affected by the disease, and the cellular dysfunction produces the symptoms. In juvenile diabetes, the insulin-producing islet cells of the pancreas are destroyed. Insulin is critical to the proper regulation of sugar by the body, and its absence causes the severe condition called diabetes. Researchers want to coax embryonic stem cells into becoming healthy insulin-producing cells. These cells might then be transplanted into people with diabetes to produce the insulin they lack. Researchers are also interested in producing stem cells that malfunction exactly like the diseased cells in order to understand fundamental aspects of the disease and also to test treatments.

2006 Stem Cells Lecture 4

Tue, 06 Mar 2007 14:00:00 -0500

"Stem Cells and the End of Aging " by Nadia Rosenthal, Ph.D.
Human tissues vary in their ability to heal and regenerate. The nervous system has weak powers of regeneration, while the skin is quick to make new cells for repair. Mammalian muscle cells are intermediate in their ability to regenerate. Human muscle can regenerate in response to minor wounds and normal wear and tear, but humans will not grow a new bicep, for example, in response to amputation. The heart is the most important muscle in the body and yet has feeble regenerative capabilities. Research into the wholesale production of new replacement organs and limbs is in its infancy, but research into enhancing normal levels of regeneration is progressing rapidly. Recent discoveries concerning the location and characteristics of adult stem cells and the signals that wounded tissue produces to activate stem cells have increased our understanding of regeneration. Insulin-like growth factor 1 (IGF1) is an example of an important stem cell communication molecule. If the activity of the growth factor is experimentally enhanced, muscle regeneration improves.

2006 Stem Cells Discussion Session

Tue, 06 Mar 2007 13:00:00 -0500

Stem Cell Research: Policies and Ethics
A 50-minute discussion between students and the lecturers, moderated by Dr. Jonathan D. Moreno, director of the Center for Biomedical Ethics at the University of Virginia, and Dr. Debra J.H. Mathews, assistant director for science programs at Johns Hopkins University.

1998 Cardiovascular Diseases Lecture 1

Mon, 05 Feb 2007 17:00:00 -0500

"Brave Heart: Circle of Life" by Christine E. Seidman, M.D.
The heart acts as a dual pump, sending oxygen-depleted blood to the lungs to be reinvigorated and pumping oxygen-rich blood to vital organs throughout the body. A collection of specialized cells, called the pacemaker, coordinates the contraction of the heart’s four chambers by generating electrical impulses that spread all over the heart. Hormonal secretions alter heart activity in various ways, as can risk factors such as smoking and male gender.

1998 Cardiovascular Diseases Lecture 2

Mon, 05 Feb 2007 16:00:00 -0500

"Telltale Genes: Charting Human Disease" by Richard P. Lifton, M.D., Ph.D.
Why children resemble their parents has intrigued scientists for thousands of years. The discovery of DNA as the basis of heredity led to an explosive growth of knowledge about the human genome and allowed the identification of genes that predispose people to different diseases. The Human Genome Project aims to determine the entire 3 billion base pair sequence of DNA and ultimately identify all the genes, estimated between 60,000 and 100,000, that define humans.*

*The first draft of the human genome was published in 2001. Most researchers have revised their estimates of the number of genes in the human genome downward, many to as low as 30,000.

1998 Cardiovascular Diseases Lecture 3

Mon, 05 Feb 2007 15:00:00 -0500

"Heartbreak: Of Mutations and Maladies" by Christine E. Seidman, M.D.
Although heart disease typically occurs after middle age, seemingly fit and healthy young individuals can die suddenly from unrecognized heart disease. In many cases, the culprit is hypertrophic cardiomyopathy, a disorder characterized by thickening of the ventricular muscle. It is caused by mutations in genes that encode proteins of the sarcomere, the contractile apparatus of muscle cells.

1998 Cardiovascular Diseases Lecture 4

Mon, 05 Feb 2007 14:00:00 -0500

"The Kidney's Tale: Of Salt and Hypertension" by Richard P. Lifton, M.D., Ph.D.
High blood pressure, or hypertension, contributes to heart attacks, strokes, and kidney failure. Since many factors regulate blood pressure, it has been difficult to determine the cause of hypertension. Molecular genetic approaches have identified genes that, when mutated, cause either increased or decreased blood pressure. Interestingly, all the genes identified to date function by regulating the amount of salt and water retained by the kidney.

2004 Obesity Lecture 1

Thu, 04 Jan 2007 17:00:00 -0500

"Deconstructing Obesity" by Jeffrey M. Friedman, M.D., Ph.D.

Over the course of a year, a typical American consumes nearly a million calories and yet weight generally fluctuates very little. That's because the body has mechanisms for keeping track of calories and carefully balancing food intake and energy output. And that's what makes dieting so difficult. As we cut calories and lose weight, our metabolism slows, making it more difficult to take off the pounds. Obesity, then, is not the result of a complete lack of discipline but is largely a function of biology.

Studies of twins and adopted children show that obesity is heritable and that genes play an important role in determining body size. In the past decade, researchers have discovered some of these genes and are learning how they influence eating and body weight. Studying mice that are massively obese, Dr. Friedman and his colleagues identified the gene for leptin, a hormone produced by fat cells. Leptin-named after the Greek word for "thin"-feeds into the circuit of neurons in the brain that controls eating and energy expenditure. When we lose weight, leptin concentrations fall. This dip in leptin levels instructs the body to find more food. For this reason, most diets eventually fail.

Dr. Friedman introduces the genes and circuits that control appetite. By understanding how these systems interact with the environment, researchers might someday develop treatments for obesity.

2004 Obesity Lecture 2

Thu, 04 Jan 2007 16:00:00 -0500

"Understanding Fat: Syndrome X and Beyond" by Ronald M. Evans, Ph.D.

When it comes to weight control, appetite isn't everything. Our relative leanness-or lack thereof-also depends on how our bodies balance the storage and burning of dietary fat. And what we eat can make a big difference. Fat, it turns out, carries instructions about how it should be used. Saturated fats, the type found in meat and dairy products, are hard for cells to break down, so they tend to get tucked away. Unsaturated fats, found in olive oil and other plant oils, are readily consumed for energy. What's more, they direct the body to burn more fat.

Having too much fat lying around is bad because it can trigger insulin resistance—the first step on the path to diabetes. Fat encourages muscle to reject glucose as an energy source. To keep this sugar from building up in the blood, the pancreas produces extra insulin. Over time, however, the pancreas becomes overworked and can no longer compensate. So blood sugar rises and diabetes develops.

Exercise improves the situation, because the stretching of muscle fibers provokes cells to take up glucose, removing it from the blood. Unfortunately, more weight usually goes hand in hand with less exercise-even in mice. Rodents treated to a "Western" diet, rich in fat, grow pudgy and sluggish, sitting more often than they scurry. In humans, a high-fat diet coupled with poor exercise leads to syndrome X, a metabolic disorder characterized by insulin resistance, high blood pressure, and heart disease.

Dr. Evans describes how fat communicates with muscle and how diet and exercise influence that relationship, promoting good health or precipitating disease.

2004 Obesity Lecture 3

Thu, 04 Jan 2007 15:00:00 -0500

"Balancing the Fat Equation" by Ronald M. Evans, Ph.D.

Like most things in the body, metabolism is governed by a complex interaction among genes. In particular, a family of proteins called PPARs (for peroxisome proliferator-activator receptors) controls how the body uses sugar and fat. One member of this family, PPAR-gamma, acts as a master switch that drives the formation of fat cells and regulates the storage of fat. The receptor snatches fat from the blood and squirrels it away inside fat cells. By whisking fat from the blood, PPAR-gamma encourages muscle to burn sugar and allows the body to remain sensitive to insulin. Drugs that activate PPAR-gamma are currently used to treat diabetes. Although they don't help people lose weight, the drugs do restore patients' sensitivity to insulin.

A sister protein, called PPAR-delta, regulates how muscles burn fat. When kept on a high-fat diet, mice that lack PPAR-delta become obese. Mice that are engineered to produce an overactive version of the receptor in their muscle tissue remain sleek and lean. PPAR-delta revs up cellular fat-burning pathways and beefs up the animals' slow-twitch muscle mass. This type of muscle, highly developed in marathon runners and migrating birds, prefers to use fat as an energy source. The engineered animals put this muscle to good use. When placed on a rodent-sized treadmill, these "marathon mice" will run twice as far as their normal relatives.

Dr. Evans reviews how PPARs regulate body weight-and how drugs that stimulate PPARs might help people slim down and improve their health without altering their appetite.

2004 Obesity Lecture 4

Thu, 04 Jan 2007 14:00:00 -0500

"Exploring Obesity: From the Depths of the Brain to the Far Pacific" by Jeffrey M. Friedman, M.D., Ph.D.

By four years old, the boy weighed 90 pounds and consumed more than 1,100 calories in a single sitting-approximately half the recommended daily intake for an adult. Genetic testing revealed that the child possessed a rare mutation that disabled his leptin gene. Without the hormone, he kept gaining weight because his body told his brain that he was starving. When doctors treated the boy with leptin, his calorie intake was slashed by 84 percent and he eventually got down to a normal weight for his age.

In studies of obese mice, Dr. Friedman has found that leptin actually restructures the brain, rewiring the neural circuit that controls feeding. The hormone reinforces the nerve cells that encourage the body to slenderize and prunes the neurons that compel eating.

Leptin isn't the whole story. For most of us, a combination of genes regulates our weight. These powerful systems are part of our genetic heritage. Some researchers think that such "thrifty genes" provided our ancestors with a survival strategy for coping with famine. Individuals who stored calories in times of plenty could avoid starvation when food grew scarce. Thus, obesity could be a product of these genes that evolved to keep us alive.

Dr. Friedman describes his continuing hunt for the genes that make us fat, research that has carried him to a small island in the Pacific where obesity is rampant. By analyzing DNA collected from all the adults on the island, Dr. Friedman hopes to learn more about why some people are overweight while others are lean.

2004 Obesity Discussion Session

Thu, 04 Jan 2007 13:00:00 -0500

Student Discussion Session on Obesity

A 45-minute question-and-answer session with the lecturers and students attending the Holiday Lectures on Science. The session is moderated by Sally Squires, columnist for the Washington Post.

2005 Evolution Lecture 1

Tue, 29 Nov 2005 04:00:00 -0500

"Endless Forms Most Beautiful" by Sean B. Carroll, Ph.D.

The Darwinian revolution was the first revolution in biology. This lecture traces the discovery of evolution through Charles Darwin’s long voyage, many discoveries, and prodigious writings. It is a dramatic story of how a medical school dropout and future clergyman transformed our picture of nature and our place in it. Darwin developed two great ideas in The Origin of Species that have shaped 150 years of evolutionary biology: the descent of species from common ancestors and their modification through natural selection. Darwin also introduced the concept of the “fittest,” but how are the fittest made?

The second revolution in biology was triggered by discoveries in genetics. Genetic variation, selection, and time combine to fuel the evolutionary process. The action of selection is now visible in DNA, both in preventing injurious changes and in favoring advantageous changes in traits.

2005 Evolution Lecture 2

Tue, 29 Nov 2005 03:00:00 -0500

"Selection in Action" by David M. Kingsley, Ph.D.

The products of natural, and human, selection are all around us. Humans have transformed wild plants into useful crops by selective breeding. Human selection has also produced pets and other domesticated animals with sizes and shapes very different from their wild ancestors. Controlled genetic crosses can be used to identify and locate the genes responsible for artificial selection in domesticated species. Genetic crosses in maize and dogs, for example, suggest that few genetic changes are needed to dramatically transform the shape and structure of plants and animals.

Natural selection in wild populations can also generate amazing diversity in a surprisingly short amount of time. Ocean stickleback fish, for example, colonized numerous freshwater streams and lakes produced by retreating glaciers after the last Ice Age. Differential survival and reproduction under natural selection have generated dramatic changes in morphology, physiology, and behavior as the fish adapted to different food sources, predators, and water conditions. Genetic studies of recently evolved freshwater fish confirm that many evolutionary traits are controlled by relatively few genes. It appears that natural populations, like domesticated populations, can evolve rapidly under the influence of a few simple genetic changes.

2005 Evolution Lecture 3

Tue, 29 Nov 2005 02:00:00 -0500

"Fossils, Genes, and Embryos" by David M. Kingsley, Ph.D.

Recent studies have identified important genes that direct embryonic development. Specific developmental regulators control the formation of heads and tails, backs and bellies, forelimbs and hindlimbs, and the left and right sides of the body.

Many key developmental genes are conserved among animals that look very different. A diversity of body forms can emerge from changing where and when these shared developmental regulators are expressed. For example, fins and limbs have been extensively modified in many different animals. Major changes in the fins of stickleback fish occur by altering the expression pattern of a major developmental control gene involved in hindlimb development. Intriguingly, fish evolving independently in widely separated waters have alterations in the same basic genetic and developmental elements. Fossils suggest that similar developmental mechanisms were used in animals that evolved millions of years ago.

The great extent of shared developmental machinery reveals a deep common ancestry for living forms and makes it possible to discover general rules of evolution from highly detailed studies of select organisms.

2005 Evolution Lecture 4

Tue, 29 Nov 2005 01:00:00 -0500

"From Butterflies to Humans" by Sean B. Carroll, Ph.D.

The story of animal evolution is marked by key innovations such as limbs for walking on land, wings for flight, and color patterns for advertising or concealment. How do new traits arise? How has the great diversity of butterflies, fish, mammals, and other animals evolved?

The invention of insect wings and the evolution of their color patterns are beautiful models of the origin of novelty and the evolution of diversity. This lecture explores how new patterns evolve when “old” genes learn new tricks.

Old genes learning new tricks also applies to our own species and the evolution of traits that distinguish us from earlier hominids and other apes: our big brains, bipedal locomotion, and speech and language. The complete picture of human evolution involves new information emerging from the fossil record, genetics, comparative physiology, and development. Despite immense advances in evidence and understanding, there remains a societal struggle with the acceptance of our biological history and the evolutionary process, the roots of which are discussed in this lecture.

2005 Evolution Discussion Session

Tue, 29 Nov 2005 00:00:00 -0500

Student Discussion Session on Religion and Evolution

A 70-minute discussion session on reconciling religious beliefs with evolutionary theory, moderated by HHMI investigators Sean B. Carroll, Ph.D., and David M. Kingsley, Ph.D., along with James Wiseman, O.S.B., of St. Anselm's Abbey in Washington D.C., and Michael Ruse, Ph.D., of Florida State University.