HHMI's Holiday Lectures on Science
Summary: HHMI's Holiday Lectures on Science The Howard Hughes Medical Institute is a philanthropy that supports biomedical research and science education. As part of its mission to strengthen science education, the Institute presents the Holiday Lectures on Science, an annual series that brings the latest developments in a rapidly moving field of research into the classroom. These lectures are videotaped and technical, but even the lay person can learn from them. Audio files are available, but you do lose the visual aids. However, they are still useable. Previous subjects have included, dengue, RNA, and the idea of quorum sensing which is how bacteria decide when to attack, or fireflies coordinate their flashing sequence.
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.
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.
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.
Dr. Bonnie Bassler discusses antibiotics development, quorum sensing, and other topics related to bacteria in a question-and-answer session with a student audience.
Dr. Baldomero Olivera discusses various aspects of the biology of the venomous cone snails in a question-and-answer session with a student audience.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.