Demystifying Medicine 2018
Tuesdays: January 9 through May 8
4:00pm - 6:00pm
Building 50 Conference Room
(unless otherwise noted)
January 9 - New Viral Diseases, Universal Vaccines, and Removing Agents from the Blood Supply
The traditional response to infectious diseases has been to obtain epidemiologic information, identify the organism, seek pharmacologic treatment, develop a vaccine, educate the public...and eventually move on to the next ID crisis. This has been the route with all relatively recent infections including Ebola, SARS, HIV, HBV, HCV, HAV, Influenza, Dengue, XXX, West Nile Virus and drug-resistant bacteria and parasites, etc.
This time honored process has produced spectacular results in most cases; however, it is based on the principle that the clinical disease occurs first and the response is rapid, expensive and, so far, successful.
The genomic (and other -omics) era has prompted inquiry into techniques for rapid detection of new infections, world wide public health measures for education and prevention, and consideration of challenging questions such as:
~ universal vaccines for diseases, such as influenza, in which every epidemic is causes of a different molecular variant;
~ techniques for treating blood and blood products obtained in Blood Banks for removal of all nucleic acid-containing materials (ie "sterilization of the blood").
~ other imaginative approaches are also "in the works" and may herald a new and effective way to prevent and treat infectious diseases...yet to come!
Anthony Fauci, MD Director of NIAID, and Robert Allison, MD Chief of the Infectious Diseases Section in the NIH Clinical Center's Department of Transfusion Medicine, are in the forefront of these efforts which will be presented in the first 2018 session of Demystifying Medicine to be held January 9th 4:00-6:00pm Building 50 ground floor auditorium. All Demystifying Medicine sessions are available live on line for NIH personnel and, several days later, appear on NIH Videoarchive for world wide access and through YouTube.
January 16 - Is Childhood Leukemia Curable? Challenges and Milestones in Current Approaches
As background for today's and other cancer-related DEMYSTIFYING medicine sessions, I refer you to Mukahjees' brilliant book..."Emperor of All Maladies" 2010 Pulitzer Prize autobiography of cancer.
The history of cancer is one of the most dramatic in medicine.
In the early 20 Century, surgery was the only treatment modality. The results were terrible.
The global view was stated by the poet Hilaire Belloc:
Physicians of the utmost fame
were called at once, but when they came
They answered, as they took their fees
There is no cure for this disease
By the middle of the 20th C, not much had changed...emphasis was still restricted to surgery although radiation had been introduced.
The overall view was that of William B Castle:
Palliation of cancer is a daily task,
its cure a fervent hope
In 1950...an authoritative review announced that the only advances in treatment were less radical surgery and introduction of radiation. There was no new conceptual approach to therapy.
Because therapy was of little use, cancer fell largely in the domain of pathologists; the most important of whom was Rudolph Virchow who, by the time of his death in 1902, had classified solid tumors by their cell of origin, differentiated acute from chronic types...as well as what he called cancers of the blood or leukemias.
Virchow other halcyon contribution was the proposition that cancers are characterized by unrestricted growth.
Until recently, these hallmark contributions...morphologic characterization and unrestrained growth have remained remarkably intact. More recent molecular studies indicate that morphologic identity does not imply functional identity. Molecular heterogeneity n a tumor confers different function...and is the basis for the concept of individualized medicine and site directed therapy.
Of all leukemias, the most terrifying is acute lymphoblastic leukemis in children.. In older individuals, acute myelogenous leukemia AML acquires this mantle.
The major conceptual breakthrough occurred in the late 1950s when EMMANUEL FARBER, Professor of Pathology at Harvard quantified the rapid cell renewal in ALL and proposed that it required B12 and/or folic acid...which had been purified and shown to be required in hematopoiesis. B12 deciciency was shown to be the cause of pernicious anemia.
Initially, Based on a hypothesis that excess folate would rwduce cell growth, Farber administered folate to children with ALL. The results were disastrous; cell growth was increased. He then proposed that folate deficiency would retard leukemic growth. ALL children were treated with amethopterin, a synthetic competitive inhibitor of folate. AMAZINGLY hematologic improvement occurred, many symptoms disappeared and the drug induce remission last for at best a few months. THIS WAS THE DAWN OF CHEMOTHERAPY OF CANCER and creation of a neww therapeutic paradyme.
Subsequent studies and clinical trials at NIH by Frei and Freirich at NCI NIH expanded the concept of chemotheraphy. Initial trils were devoted to acute leukemia in children. This began the era of testing single, then multiple chemotherapeutic agents and balancing their severe toxicity against outcome.
THE CONCEPT THEN...AS NOW...reflects Shakespeare's writing in Hamlet:
"Diseases desperate grown
By desperate appliance are resolved
or Not at all"
In the present, advances continue at a rapid pace. They now involve advanced chemotherapy, personalized medicine based on molecular genomics...and, most recently, the interplay with the immune system.
So, we welcome Dr. Nirali Shah and trust that she will update us into the exciting world of challenges in cancer biology and also inform as to whether acute leukemia, particularly in children, has been cured.
January 23 - Sexually Transmitted Diseases: Situation Getting Worse...and Also Better
Venereal Disease as a designation was replaced several years ago by Sexually Transmitted Diseases probably to reflect widespread societal changed associated with sexually-related disease transmission. Historically, syphilis, gonorrhea and lymphogranuloma venereum were the major "venereal" diseases associated with widespread distribution and acute weed chronic complications. Until discovery of Ehrlich's Magic Bullet ("606" Neosalvarsan), which was an organic arsenical, syphilis was treated with mercury ("One night with Venus, and a lifetime with Mercury") which was painful and of limited success. Hunter, the great English anatomist, thought that syphilis and gonorrhea were the same disease because he acquired both when self-injected with what he thought was only gonorrhea secretion! "Gonorrhea" (literally "flow of semen") was shown by Neisser, who performed Koch's postulates in uninfected women (!) to result from gonococcal infection.
Penicillin changed everything as it became cheap, available, highly effective in syphilis resulting in leas public concern with syphilis and gonorrhea as "serious diseases". Chronic syphilis of the nervous system (take dorsals, Korsakoff's syndrome) and circulation (aneurysm) virtually disappeared.
However, the problem of STD continues to increase and present global challenges due to "new" diseases (HIV AIDS. HBV, HCV), recognition of other agents (Chlamydia, herpes and HPV) and emergency of pencillin-resistant strains of gonococcus and treponema.
Association of sexually-transmitted HIV, HBV, HCV) with various cancers added a new dimension to complications of STDs. However, the major finding that HPV strains result in cancer of cervix, vagina, other female organs....and, related to oral and anal sex, are major factors in nasopharyngeal and anal cancers.
On the progress side, is discovery of effective vaccines for HPV...which raise other questions of specificity and societal acceptance.
January 30 - Why is HIV Still a Biologic and Epidemiologic Challenge Worldwide?
What global viral disease(s) is apparently "cured" by engineered pharmaceuticals?
NO it is unfortunately NOT HIV.
Possibly the most significant advance in medicine in the past 20 years has been conversion off HIV AIDS from a widespread lethal disease to a "manageable" chronic disease. Normal lifespans are now noted in HIV patients who receive drug-therapy directed to specific components of the virus and the host response. BUT there are NO (or very very few) "cures"....meaning that the virus has been fully eliminated. Furthermore, lapses in therapy result in re-emergence of HIV. Thus, current treatments are lifelong. In addition, we have the therapeutic means to control and, to some extent prevent, HIV.
Given these facts. who are there millions of new HIV cases each year, inability to "cure" and remaining mysteries about prevention?
These challenging public health issues remain the subject of intensive basic biologic studies of the virus and the host response. Quasi-species, multiple new mutations, biologic "hiding" places, drug resistance and the basic mechanisms of vial"immune system interaction remain as challenging issues......probably having importance in other viral diseases and out inability to "cure" most of them.
February 6 - The New Frontier: Immunotherapy of Cancer
The "traditional" modus operandi for treatment of cancers of solid organs such as liver, lung, colon, pancreas and brain has been surgery, when possible, or destruction of cancer cells by radiation and/or chemotherapy. Although success has occurred in some situations, the overall effects on survival are frequently marginal.
Other therapeutic approaches have evolved based on entirely different mechanisms:
(1) The late Judah Folkman proposed and demonstrated that inhibition of angiogenesis can prevent tumor growth and metastasis. Anti-VEGF drugs have had significant effects in some cancers, particularly breast. Inhibition of angiogenesis is still being researched.
(2) The molecular-genomic era has resulted in demonstration that almost all cancers have functional mutations in critical growth-controlling genes; some of these mutations are specific targets for synthesized drugs. Cancer cell mutations are not unique for specific organ tumors and change with time, drug resistance and metastasis. These findings form the basis for designing "personalized" treatments.
(3) Immunotherapy is the newest, exciting and challenging therapy for cancer. The field emerged at NIH when Steve Rosenberg/NCI began to treat melanoma patients with IL-2 and observed rare cancer regression which persisted. Tumor-infiltrating T cells were shown to attack cancer cells. T cells isolated from cancer patients are provided with receptors which recognize surface markers on the cancer cells. This treatment is increasingly being used in lymphoma patients. The concept of cell-transfer immunotherapy for patients with any type of cancer is the "brave frontier" of cancer immunology and therapeutics.
February 13 - Does Inflammation Cause Cardiovascular Disease? If So, How?
Although it is not proven that inflammation directly causes cardiovascular diseases, chronic, low-grade inflammation is epidemiologically linked to all stages of atherosclerosis which underlies myocardial infarction, stroke and peripheral artery disease. Several markers of inflammation, such a C-reactive protein and other acute phase reactants, are considered as risk factors in atherosclerotic cardiovascular disease.
How good is this evidence? What is the mechanism linking inflammation and atherosclerosis? Are there therapeutic implications regarding control of inflammation (ie aspirin) and prevention/treatment of atherosclerotic cardiovascular disease? Does inflammation help to explain the high mortality in cardiovascular atherosclerotic disease even when hypertension, hypercholesterolemia and other factors are "controlled"?
Alan Remaley, MD, PhD and Nehal Mehta, MD of the National Heart Lung and BloodInstitute will analyze these and other challenging questions regarding the number one killer disease in US.
February 20 - The Microbiome in Man, Animals, and Disease: Where Do We Stand?
February 27 - The Great Neglected Diseases
The Great Neglected Diseases (GND) is the topic for this session of Demystifying Medicine on Tuesday February 27th building 50 ground floor auditorium 4:00-6:00pm.
These diseases are worldwide...particularly in under developed countries....but also, in this thinking world confronted with global warming, in "developed" countries albeit not so frequently.
The GNDs are mainly parasitic....worms, amoebae, bacterial, viral and others.
The confront the major biologic question: How does parasitism develop? How does a parasite "live" in the host, consumes host energy and, hopefully, does not kill the host? Each of these chronic diseases affects millions of people and dramatically let's their health and eventually results in death....when occurring simultaneously with impaired nutrition, multiple infection and other diseases.
Deciphering the basis of parasitism involves complex immunology, extraordinary life cycles (why? how?) and challenges development of therapy, prevention and eradication.
Speakers: Alan Sher, PhD NIAID
Thomas Nutman, MD NIAID
March 6 - Diabetes and Artificial Sweeteners
March 13 - Brave New World: Imaging from the Cosmos to the Molecule
March 20 - The Challenge of Malaria: The World's Number One Killer
A study published earlier this month highlighted the dangers of bees, wasps, and dogs - the "deadliest" animals in North America, killing hundreds of Americans annually. Yet such dangers are dwarfed by the Anopheles mosquito, the buzzing vector of the Plasmodium Vivax parasite, which causes malaria and kills more than a million people each year, mostly children, and sickening far more.
This week's Demystifying Medicine lecture delves into exciting advances that represent a new direction in malaria control: breaking the life-cycle of the Plasmodium Vivax parasite in vivo, as opposed to in the environment. The lecture is Tuesday, March 20, from 4:00 to 6:00 p.m. in the Building 50 ground-floor conference room. The speakers are Peter Crompton, MD, MPH, of NIAID, and Photini Sinnis, MD, of the Johns Hopkins Bloomberg School of Public Health.
Previous gains have been made in mosquito population control and the use of mosquito bed netting, as well as malaria treatments based on quinidine, a natural substance found in cinchona tree bark. More recently, the focus has turned to creating a vaccine, but progress has been meager.
Why such limited progress? One mystery associated with Plasmodium Vivax infection is long-term accumulation of the merozoite phase in intracellular compartments in hepatocytes. The parasite can remain for years in these compartments and, for reasons not fully understand, can burst forth again as spherozoites, which destroy erythrocytes thereby producing the clinical disease.
Yet substantial effort has been made to understand the molecular and immunologic basis of infection. The greatest gain has been awareness of the extraordinary games the malarial parasite plays to avoid our best effort to eradicate and treat the disease. The hope is that these new insights will lead to therapeutic targets in the complex life cycle of the malarial parasite and a way to overcome drug resistance.
Demystifying Medicine lecture should be of particular interest among immunologists and those interested in vaccine development, drug resistance, public health, or the path of basic science to cures, as well as anyone who just plain hates mosquitos.
March 27 - Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease): Are We Making Progress?
Theoretical physicist Stephen Hawking died on March 14 at the age of 76, having defied expectations and living more than 50 years with amyotrophic lateral sclerosis (ALS), a disease that hijacked his body but not his mind. How did Hawking survive for five decades and excel intellectually, albeit wheelchair-bound, while others have succumbed far more quickly to ALS's destruction of motor neurons in the brain and spinal cord. Are there effective treatments on the horizon to slow the progression of ALS? What hope can we provide, responsibly, to ALS patients and their families?
These will be topics discussed in the next Demystifying Medicine lecture, "Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease): Are We Making Progress?", by Bryan Traynor. M.D. (NIA) and Mary Kay Floeter, M.D., Ph.D. (NINDS) on Tuesday, March 27, from 4:00 to 5:30 p.m. in the Building 50 conference room.
ALS causes the motor neurons in the brain and spinal cord to shrink and disappear, so that the muscles no longer receive signals to move. The damage is swift and profound: Upper motor neurons send messages from the brain to the spinal cord, and lower motor neurons send messages from the spinal cord to the muscles. Thus, ALS affects a person's ability to walk, lift, point, or even breath. Those with ALS often die from respiratory failure, which nearly took Hawking's life in 1985 and led to the loss of his voice.
Someone with ALS, even at an advanced stage, can see, hear, smell, feel and touch. But occasionally parts of the brain involved in memory and learning are affected. There is no effective treatment or prevention, although NIH are working on this and are making progress on the disease at a fundamental level. Famous people who had ALS include Mao Zedong (although not officially confirmed), actor David Niven, politician Jacob Javits, Gen. Maxwell Taylor, and, of course, baseball legend Lou Gehrig.
April 3 - Compulsive Disorders: Mechanisms and Management
What's the connection between habits (nail-biting, over-eating), compulsive disorders (tics, excessive hand-washing) and addiction (gambling, drug abuse). They all may share an underlying neuronal mechanism as a response to anxiety.
At the next Demystifying Medicine lecture, we will discuss the fascinating field of obsessive and compulsive disorders and its deep connections to the relatively benign "bad" habits we all have as well as deadly addictive behavior in all its forms. The title of the lecture is "Compulsive Disorder: Mechanisms and Management" by Antonello Bonci, M.D. NIDA Scientific Director, and Veronica Alvarez, Ph.D., chief of the NIAAA Laboratory on the Neurobiology of Compulsive Behavior.
The lecture is 4:00 to 5:30 p.m. in the Building 50 first-floor conference room. All are welcome; live videocasts also will be available at http://videocast.nih.gov.
Compulsive disorders and neuroscience was one of six research areas identified by the NIH intramural scientific directors in 2017 as being ripe for development at the NIH. The field combines biology with imaging and behavioral science, making this a topic of interest to many at the NIH, including those involved in nutrient-related chronic diseases.
April 10 - Use of Stem Cells for Regenerative Medicine
The blind shall see; the lame shall walk; organs will grow anew. Such has been the promise...and hype...of stem-cell-based regenerative medicine. Yet some of these promises have been coming to fruition, particularly in the realm of retinal diseases and bone development.
At the next Demystifying Medicine lecture, we will discuss recent advances in regenerative medicine with a focus on induced pluripotent stem cells (iPSC). A dazzling series of breakthroughs, many originating from NIH labs, is having profound implications for biology and continues to prompt imaginative studies for clinical application.
The lecture, "Use of iPSC for Regenerative Medicine," is April 10 from 4:00 to 5:30 p.m. in the Building 50 first-floor conference room. The speakers are Kapil Bharti, Ph.D., head of the NEI Section on Ocular and Stem Cell Translational Research, and Pamela Robey, Ph.D., NIDCR, senior investigator in the NIDCR sections on Skeletal Biology and on Craniofacial, Developmental, Cell, and Matrix Biology.
All are welcome; a live videocast also will be available at http://videocast.nih.gov.
Lecture summary: We all begin as a single fertilized egg cell, a primordial embryonic stem cell capable of differentiating into specific organ stem cells that form every tissue and organ in our bodies. Different tissues have highly varied rates of cellular turnover and replacement from organ-specific stem cells to maintain functional homeostasis. For example, skin and intestinal mucosal cells rapidly turn over within 1-2 days, whereas hepatocytes divide once a year and neurons were initially thought not to turnover ever.
Into this dynamic state of cell biology, Japanese scientist Shinya Yamanaka made an amazing discovery, demonstrating that fibroblasts could be reprogrammed by four transcription factors to become an induced pluripotent stem cell capable of being processed into organ-specific stem cells. The discovery earned Yamanaka a 2012 Nobel Prize. Each of the various types of stem cells has been shown to replace normal tissues in animal studies. As such, scientists around the world and around NIH are investigating this potential to cure diseases and extend healthy lifespans.
For more information, please visit the Demystifying Medicine website at https://demystifyingmedicine.od.nih.gov.
April 17 - The Opioid Epidemic: How, Where, and What Can Be Done?
Overdose deaths from opioid use have nearly quadrupled since the year 2000, and opioids now kill more people each year in the United States than guns or car accidents. We know how the opioid crisis came to be; we know what opioids do to the brain. Now we must put our heads together to curb the epidemic fast.
At the next Demystifying Medicine lecture, two of the most prominent figures in the national opioid discussion - NIDA Director Nora Volkow, M.D., Ph.D., and NINDS Director Walter Koroshetz, M.D. - describe in detail the state of the opioid crisis and what NIH is doing about it. Come to the lecture to get plugged in to one of the most pressing public health emergencies of our times.
The lecture, "The Opioid Epidemic: How, Where, and What Can Be Done?" is April 17 from 4:00 to 5:30 p.m. in the Building 50 first-floor conference room. All are welcome; a live videocast also will be available at http://videocast.nih.gov.
Lecture summary: Every day, more than 115 Americans die after overdosing on opioids, a four-fold increase since 2000, and the numbers continue to climb. Toward this effort, NIH has nearly doubled funding for research on pain and on opioid misuse and addiction from approximately $600 million in fiscal year 2016 to $1.1 billion in fiscal year 2018, made possible from a funding boost by Congress. The focus of NIH's efforts centers on ways to reduce the over prescription of opioids, accelerate development of effective non-opioid therapies for pain, and provide more flexible options for treating opioid addiction. This lecture describes the state of the crisis, the state of our efforts, and how you can be a part of the solution.
Additional Items to Consider:
~ Acute and chronic pain is a major complaint for millions of individuals. Management is complex, depends on etiology and invariably involves medications. Classical pain-relieving medications (ie, cocaine, morphine, etc) are addictive. Therefore non-addicting medications were sought.
~ In the late 1990s, pharmaceutical companies reassured the medical community that patients would not become addicted to opioid pain relievers and healthcare providers began to prescribe them at greater rates. Wow...were the companies wrong!
~ Increased prescription of opioid medications led to widespread misuse of prescription and non-prescription opioids before it became clear that these medications could indeed be highly addictive.
~ In 2017 HHS declared a public health emergency and announced 5-Point Strategy To Combat the Opioid CrisisOpioid Crisis
~ Devastating consequences of the opioid epidemic include increases in opioid misuse and related overdoses, as well as the rising incidence of newborns experiencing withdrawal syndrome due to opioid use and misuse during pregnancy.
~ Opioid overdoses accounted for more than 42,000 deaths in 2016, more than any previous year on record. An estimated 40% of opioid overdose deaths involved a prescription opioid.
April 24 - Prenatal Genomics and Fetal Gene Therapy
May 1 - "Bridge Building," Careers for PhD and MD Fellows
PhD- and MD-level fellows are encouraged to come to the next Demystifying Medicine lecture for a discussion about (gulp!) the future. Know your career options; there may be paths that you don't realize.
This penultimate lecture in this year's Demystifying Medicine series, titled "Bridge-Building Careers for PhD and MD Fellows," will feature Michael Gottesman, M.D., the Deputy Director for Intramural Research; Jonathan Yewdell, M.D., Ph.D., a senior investigator in NIAID's Cellular Biology and Viral Immunology Section; and Win Arias, M.D., scientist emeritus and creator of the Demystifying Medicine course.
The lecture is on May 1 from 4:00 to 5:30 p.m. in the Building 50 first-floor conference room. All are welcome; a live videocast also will be available at http://videocast.nih.gov.
The workforce of the future will be far more diverse, and team science much more common than now. Learn what skills you need beyond basic science to prepare yourself.
May 8 - The National Institutes of Hope
NIH Director Francis Collins will present this season's final Demystifying Medicine course, a talk titled "The National Institutes of Hope," on Tuesday, May 8, from 4:00 to 5:30 p.m. in the Building 50 first-floor conference room.
Did you miss the opportunity to ask the NIH Director questions during his Reddit "Ask Me Anything" event on April 20? Well, now is your chance to hear about the broad range of research at the NIH and pose questions to one of the nation's most celebrated scientists. All staff are welcomed. Trainees will particularly benefit from this interchange with the NIH Director. Really, why else are you here if not to engage with world-class scientists?
For questions about the course, please contact email@example.com.
This web page was last modified on 8 May 2018.