Synovial joints (or diarthroses, or diarthroidal joints) are the most common and most movable type of joints in the human body. As with most other joints, synovial joints achieve movement at the point of contact of the articulating bones.
Structural and functional differences distinguish synovial joints from cartilaginous joints (synchondroses and symphyses) and fibrous joints (sutures, gomphoses, and syndesmoses). The main structural differences between synovial and fibrous joints is the existence of capsules surrounding the articulating surfaces of a synovial joint and the presence of lubricating synovial fluid within that capsule (synovial cavity).
Structure
Articular capsule: The fibrous capsule is continuous with the periosteum of bone. It is also highly innervated but avascular (lacking blood and lymph vessels)
Articular cartilage: lines the epiphyses of joint end of bone. Provides the loading and unloading mechanism to resist load and shock
Synovial membrane: the inner layer of the fibrous articular capsule. The synovial membrane covers the lining of the synovial cavity where articular cartilage is absent.
Long-term potentiation (LTP) is the long-lasting improvement in communication between two neurons that results from stimulating them simultaneously. Since neurons communicate via chemical synapses, and because memories are believed to be stored within these synapses, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.
LTP shares many features with long-term memory that make it an attractive candidate for a cellular mechanism of learning. For example, LTP and long-term memory are triggered rapidly, each depends upon the synthesis of new proteins, each has properties of associativity, and each can potentially last for many months. LTP may account for many types of learning, from the relatively simple classical conditioning present in all animals, to the more complex, higher-level cognition observed in humans.
By enhancing synaptic transmission, LTP improves the ability of two neurons, one presynaptic and the other postsynaptic, to communicate with one another across a synapse. The precise mechanisms for this enhancement of transmission have not been fully established, in part because LTP is governed by multiple mechanisms that vary by such things as brain region, animal age, and species. Yet in the most well understood form of LTP, enhanced communication is predominantly carried out by improving the postsynaptic cell's sensitivity to signals received from the presynaptic cell. These signals, in the form of neurotransmitter molecules, are received by neurotransmitter receptors present on the surface of the postsynaptic cell. LTP improves the postsynaptic cell's sensitivity to neurotransmitter in large part by increasing the activity of existing receptors and by increasing the number of receptors on the postsynaptic cell surface.
LTP was discovered in the rabbit hippocampus by Terje Lømo in 1966 and has remained a popular subject of research since. Most modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of clinical research, for example, in the areas of Alzheimer's disease and addiction medicine.
Mechanism
Long-term potentiation occurs through a variety of mechanisms throughout the nervous system; no single mechanism unites all of LTP's many types. However, for the purposes of study, LTP is commonly divided into three phases that occur sequentially: short-term potentiation, early LTP, and late LTP. Little is known about the mechanisms of short-term potentiation,
Each phase of LTP is governed by a set of mediators, small molecules that dictate the events of that phase. These molecules include protein receptors that respond to events outside of the cell, enzymes that carry out chemical reactions within the cell, and signaling molecules that allow the progression from one phase to the next. In addition to these mediators, there are also modulator molecules, described later, that interact with mediators to finely alter the LTP ultimately generated.
The early (E-LTP) and late (L-LTP) phases of LTP are each characterized by a series of three events: induction, maintenance, and expression. Induction is the process by which a short-lived signal triggers that phase of LTP to begin. Maintenance corresponds to the persistent biochemical changes that occur in response to the induction of that phase. Expression entails the long-lasting cellular changes that result from activation of the maintenance signal. Thus the mechanisms of LTP can be discussed in terms of the mediators that underlie the induction, maintenance, and expression of E-LTP and L-LTP.
Jim Lockhart speaks with Anuradha Mittal of The Oakland Institute and Mark Des Marets of Northwest Resistance Against Genetic Engineering. Northwest Resistance Against Genetic Engineering www.nwrage.org From the webite SPEAKOUT! www.speakoutnow.org : Anuradha Mittal, a native of India, is an internationally renowned expert on trade, development, human rights, democracy, and agriculture issues. She is the founder and director of a policy think tank, The Oakland Institute, that works to ensure public participation and democratic debate on the most crucial economic and social policy issues that affect peoples' lives through nonpartisan research, analysis, and advocacy. Building on the identification of human rights as the foundation of global democracy, the Oakland Institute uses the rights-based approach to reframe the public debate and build an agenda for common action.
The word "laparoscopy" means to look inside the abdomen with a special camera or scope. Surgery performed with the aid of these cameras is known as "keyhole," "porthole," or "minimally invasive" surgery.
Traditional surgery requires a long incision (cut) down the center of the abdomen and a lengthy recovery period. Laparoscopic surgery eliminates the need for this large incision. As a result, you may experience less pain and scarring after surgery, more rapid recovery, and less risk of infection.
For laparoscopic prostate surgery, this technique requires five small (5-10 millimeters) incisions (or "portholes") -- one just below the belly button and two each on both sides of the lower abdomen. Carbon dioxide is passed into the abdominal cavity through a small tube placed into the incision below the belly button. This gas lifts the abdominal wall to give the surgeon a better view of the abdominal cavity once the laparoscope is in place. The surgeon is then guided by the laparoscope, which transmits a picture of the prostate onto a video monitor.
Laparoscopy is a relatively new technique for prostate removal, but it looks promising. Men who undergo this technique have less blood loss, less need for pain medicine, shorter hospital stays, quicker return to regular diet and activities, early removal of urethral catheters (tubes inserted through the penis to drain urine from the bladder), and a quicker recovery. Laparoscopy also appears to treat the cancer as well as conventional "open" procedures that are performed with a large incision.
What are the advantages of laparoscopy?
As is the case with other minimally invasive procedures, laparoscopic prostate removal has significant advantages over traditional "open" surgery:
Laparoscopy can shorten your hospital stay to one or two days. About 50 percent of men are discharged one day after surgery. (The length of stay depends on how quickly you recover and the extent of the surgery.)
There is significantly less bleeding during the operation.
You are less likely to need prescription painkillers after you leave the hospital. Patients generally need nothing more than Tylenol.
At your follow-up appointment one week after surgery, the tube — or catheter — draining your bladder will be removed if there are no signs of other problems. Occasionally, the catheter must remain in place for another week, as is routinely the case following conventional "open" surgery.
About 90 percent of patients can return to work or resume full activity in only two to three weeks.
Am I eligible for this surgery?
You are eligible if you have cancer that has not spread outside the prostate and is not very aggressive, as well as a PSA blood test less than 10. You are not eligible if you have had previous open or laparoscopic pelvic surgery, even for another reason, or a history of hormone treatment called LH-RH agonist (luteinizing hormone-releasing hormone), which reduces the size of the prostate tumor.
What are the side effects?
Medical research so far has shown the frequency of incontinence and impotence to be similar between minimally invasive surgery and open surgery -- with men usually returning to normal urinary function within three months for both types of surgeries. Both types of surgeries also have similar rates of incontinence.
Because this technique is nerve-sparing, postoperative sexual potency rate should be comparable to that of conventional open surgery. However, it is important to note that minimally invasive prostate surgery has not been in use long enough to truly assess whether or not it leads to higher rates of potency. But early results are promising.
How do I prepare for surgery?
Your surgeon will meet with you to answer any questions you might have. You will be asked questions about your health history, and a general physical examination will be performed. If your intestine requires cleaning, you will be given a prescription for a laxative medicine to take the evening before the surgery.
All patients are generally asked to provide a blood sample. Depending on your age and general health, you might also have an EKG (electrocardiogram), a chest X-ray, lung function tests, or other tests.
Finally, you will meet with an anesthesiologist who will discuss the type of anesthesia you will be given for surgery. You will also learn about pain control after the operation, which might include a PCA (patient controlled analgesia) pump.
What happens during surgery?
Your surgeon will place a small needle just below your belly button and insert the needle into your abdominal cavity. The needle is connected to a small tube, and carbon dioxide is passed into the abdominal cavity. This gas lifts the abdominal wall to give the surgeon a better view of the abdominal cavity once the laparoscope is in place. The surgeon is then guided by the laparoscope, which transmits a picture of the prostate onto a video monitor.
Next, a small incision will be made near your belly button. The laparoscope is placed through this incision and is connected to a video camera. The image your surgeon sees in the laparoscope is projected onto video monitors placed near the operating table.
Before starting the surgery, the surgeon will take a thorough look at your abdominal cavity to make sure the laparoscopy procedure will be safe for you. If the surgeon determines that the procedure will not be safe for you because of the presence of scar tissue, infection ,or abdominal disease, the procedure will not be continued.
If the surgeon decides the surgery can be safely performed, additional small incisions will be made, giving your surgeon access to the abdominal cavity. If necessary, one of these small incisions might be enlarged to remove the pelvic lymph nodes.
What happens after surgery?
You can expect to follow a liquid diet and you gradually will be able to eat solid foods. When you go home, you will follow a soft diet, which generally means no raw fruits or vegetables. A dietitian can provide more specific dietary guidelines.
Nausea and vomiting are common and occur because the intestines are temporarily disabled during anesthesia and surgery. Your doctor can prescribe medicines to relieve these symptoms, which will improve a few days after surgery.
You will be encouraged to get out of bed and walk as much as possible, starting the first day after surgery. You should steadily increase your activity after you go home. For six weeks after surgery, you should not lift or push anything over 30 pounds, and do not do abdominal exercises such as sit-ups.
Roger David Kornberg (born April 24, 1947) is an American biochemist and professor of structural biology at Stanford University School of Medicine.
Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, "the molecular basis of eukaryotic transcription." His father, Arthur Kornberg, who was also a professor at Stanford University, was awarded the Nobel Prize in Physiology or Medicine in 1959.
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Scientific Discoveries and Nobel Prize
All organisms are controlled by their genes, which are coded by DNA, which is copied to RNA, which creates proteins, which are sequences of amino acids. DNA resides in the nucleus. When a cell expresses a gene, it copies (transcribes) that gene's DNA sequence onto a messenger RNA (mRNA) sequence. mRNA is transported out of the nucleus to ribosomes. The ribosomes read the mRNA and translate the code into the right amino acid sequence to make that gene's protein.
The DNA is transcribed to mRNA by an enzyme, RNA polymerase II, with the help of many other proteins. Using yeast, Kornberg identified the role of RNA polymerase II and other proteins in transcribing DNA, and he created three-dimensional images of the protein cluster using X-ray crystallography. Polymerase II is used by all organisms with nuclei, including humans, to transcribe DNA.
Kornberg and his research group have made several fundamental discoveries concerning the mechanisms and regulation of eukaryotic transcription. While a postdoctoral fellow working with Aaron Klug and Francis Crick at the MRC in the 1970s, Kornberg discovered the nucleosome as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often termed "Chromatin" when it is bound to proteins in this manner, reflecting Walther Flemming's discovery that certain structures within the cell nucleus would absorb dyes and become visible under a microscope).Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins.
Kornberg's research group at Stanford later succeeded in the development of a faithful transcription system from baker's yeast, a simple unicellular eukaryote, which they then used to isolate in a purified form all of the several dozen proteins required for the transcription process. Through the work of Kornberg and others, it has become clear that these protein components are remarkably conserved across the full spectrum of eukaryotes, from yeast to human cells.
Using this system, Kornberg made the major discovery that transmission of gene regulatory signals to the RNA polymerase machinery is accomplished by an additional protein complex that they dubbed Mediator. As noted by the Nobel Prize committee, "the great complexity of eukaryotic organisms is actually enabled by the fine interplay between tissue-specific substances, enhancers in the DNA and Mediator. The discovery of Mediator is therefore a true milestone in the understanding of the transcription process."
At the same as Kornberg was pursuing these biochemical studies of the transcription process, he devoted two decades to the development of methods to visualize the atomic structure of RNA polymerase and its associated protein components. Initially, Kornberg took advantage of expertise with lipid membranes gained from his graduate studies to devise a technique for the formation of two-dimensional protein crystals on lipid bilayers. These 2D crystals could then be analyzed using electron microscopy to derive low-resolution images of the protein's structure. Eventually, Kornberg was able to use X-ray crystallography to solve the 3-dimensional structure of RNA polymerase at atomic resolution. The structure of RNA polymerase obtained by Kornberg is the most complex protein structure solved to date. He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins.[8]Through these studies, Kornberg has created an actual picture of how transcription works at a molecular level. According to the Nobel Prize committee, "the truly revolutionary aspect of the picture Kornberg has created is that it captures the process of transcription in full flow. What we see is an RNA-strand being constructed, and hence the exact positions of the DNA, polymerase and RNA during this process."
In 1959, Roger Kornberg's father, Arthur Kornberg, received the Nobel Prize in Physiology or Medicine for studies of how genetic information is transferred from one DNA molecule to another in a process called DNA replication. Specifically, Arthur Kornberg isolated the first enzyme capable of synthesizing DNA, bacterial DNA polymerase I, which was then the first known enzyme to take its instructions from a template, thus ensuring the conservation of genetic information during cellular growth and division. Roger Kornberg's younger brother, Thomas Bill Kornberg, discovered DNA polymerases II and III in 1970 and is now a geneticist at the University of California, San Francisco. All three Kornbergs have thus worked to understand how genetic information is put to use in cells. Roger and Arthur Kornberg are the sixth father-son pair to win Nobel Prizes.
Dr.Cameron Mello was awarded the 2006 Nobel prize for Medicine , along with colleague Dr. Andrew Z. Fire, for the discovery of RNA interference. In this video, he discusses his research and his experiences as a scientist and recent Nobel Prize
Craig Cameron Mello (born October 18, 1960) is an American biologist and Professor of Molecular Medicine at the University of Massachusetts Medical School in Worcester, Massachusetts. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Andrew Z. Fire, for the discovery of RNA interference. This research was conducted at the University of Massachusetts Medical School and published in 1998. Mello has been a Howard Hughes Medical Institute investigator since 2000.
About Speaker
Mello and Fire received the Nobel Prize for work that began in 1998, when Mello and Fire along with their colleagues (SiQun Xu, Mary Montgomery, Stephen Kostas, and Sam Driver) published a paper [3] in the journal Nature detailing how tiny snippets of RNA fool the cell into destroying the gene's messenger RNA (mRNA) before it can produce a protein - effectively shutting specific genes down.
In this Prof.Harald zur Hausen answers question from Students about HPV.Harald zur Hausen (born March 11, 1936) is a German virologist and professor emeritus. He has done research on cancer of the cervix, where he discovered the role of papilloma viruses, for which he received the Nobel Prize in Physiology or Medicine 2008.
Scientific merits
Zur Hausen's specific field of research is the study of oncoviruses. In 1976, he published the hypothesis that human papilloma virus plays an important role in the cause of cervical cancer. Together with his collaborators, he then identified HPV16 and HPV18 in cervical cancers in 1983-4. This research directly made possible the development of a vaccine which was introduced in 2006. See also HPV vaccine. He is also credited with discovery of the virus causing genital warts (HPV 6) and a monkey lymphotropic polyomavirus that is a close relative to a recently discovered human Merkel cell polyomavirus, as well as techniques to immortalize cells with Epstein-Barr virus and to induce replication of the virus using phorbol esters. His work on papillomaviruses and cervical cancer received a great deal of scientific criticism on initial unveiling but subsequently was confirmed and extended to other high-risk papillomaviruses.
He received the Gairdner Foundation International Award in 2008 for his contributions to medical science.He also shared the 2008 Nobel Prize in Medicine with Luc Montagnier and Françoise Barré-Sinoussi, who discovered the human immunodeficiency virus.
Nobel prize for medicine 2008 was Shared between Harald zur Hausen "for his discovery of human papilloma viruses causing cervical cancer" and to Françoise Barré-Sinoussi and Luc Montagnier for their discovery of human immunodeficiency virus.
Harald zur Hausen (born March 11, 1936) is a German virologist and professor emeritus. He has done research on cancer of the cervix, where he discovered the role of papilloma viruses,
Discovery of human papilloma virus causing cervical cancer
Against the prevailing view during the 1970s, Harald zur Hausen postulated a role for human papilloma virus (HPV) in cervical cancer. He assumed that the tumour cells, if they contained an oncogenic virus, should harbour viral DNA integrated into their genomes. The HPV genes promoting cell proliferation should therefore be detectable by specifically searching tumour cells for such viral DNA. Harald zur Hausen pursued this idea for over 10 years by searching for different HPV types, a search made difficult by the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.
Françoise Barré-Sinoussi
Françoise Barré-Sinoussi (born 30 July 1947) is a French virologist and director of the Unité de Régulation des Infections Rétrovirales at the Institut Pasteur in Paris, France. Born in Paris, France, Barré-Sinoussi performed some of the fundamental work in the identification of the human immunodeficiency virus (HIV) as the cause of AIDS
Luc Montagnier (born August 18, 1932) is a French virologist and joint recipient with Françoise Barré-Sinoussi and Harald zur Hausen of the 2008 Nobel Prize in Physiology or Medicine.
Discovery of HIV
Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.
Importance of the HIV discovery
Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.
Identification of virus−host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.
HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people
Ovulation is the process in the menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum (also known as an oocyte, female gamete, or casually, an egg) that participates in reproduction. Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle.
Overview
The process of ovulation is controlled by the hypothalamus of the brain and through the release of hormones secreted in the anterior lobe of the pituitary gland, (Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH)). In the follicular (pre-ovulatory) phase of the menstrual cycle, the ovarian follicle will undergo a series of transformations called cumulus expansion, this is stimulated by the secretion of FSH. After this is done, a hole called the stigma will form in the follicle, and the ovum will leave the follicle through this hole. Ovulation is triggered by a spike in the amount of FSH and LH released from the pituitary gland. During the luteal (post-ovulatory) phase, the ovum will travel through the fallopian tubes toward the uterus. If fertilized by a sperm, it may perform implantation there 6-12 days later.
In humans, the few days near ovulation constitute the fertile phase. The average time of ovulation is the fourteenth day of an average length (twenty-eight day) menstrual cycle. It is normal for the day of ovulation to vary from the average, with ovulation anywhere between the tenth and nineteenth day being common.
Cycle length alone is not a reliable indicator of the day of ovulation. While in general an earlier ovulation will result in a shorter menstrual cycle, and vice versa, the luteal (post-ovulatory) phase of the menstrual cycle may vary by up to a week between women.
Osteoarthritis , is a group of diseases and mechanical abnormalities entailing painful degradation of joints, including cartilage and the subchondral bone next to it. Clinical symptoms of OA may include joint pain, tenderness, stiffness, inflammation, and creaking of joints. In OA, a variety of potential forces -- hereditary, developmental, metabolic, and mechanical -- may initiate processes leading to loss of cartilage -- a strong protein matrix that lubricates and cushions the joints. As the body struggles to contain ongoing damage, immune and regrowth process can accelerate damage. When bone surfaces become less well protected by cartilage, subchondral bone may be exposed and damaged, with regrowth leading to a proliferation of ivory-like, dense, reactive bone in central areas of cartilage loss, a process called eburnation. The patient increasingly experiences pain upon weight bearing, including walking and standing. Due to decreased movement because of the pain, regional muscles may atrophy, and ligaments may become more lax. OA is the most common form of arthritis
Method and System for Treatment of Blood and/or Other Body Fluids and/or Synthetic Fluids using Combined Filter Elements and Electric Field Forces
In 1990, an astounding discovery was reported at Albert Einstein College of Medicine in NYC by Drs. Kaali and Wyman, resulting in Patent No. 5,188,738 being issued in 1993 entitled "Alternating Current Supplied Electrically Conductive Method and System for Treatment of Blood and/or Other Body Fluids and/or Synthetic Fluids with Electric Forces.". Their research work involved an in vitro & in vivo human Blood Electrification process, which electronically sterilizes the blood, resulting in all known pathogens, including bacteria, viruses, parasites, and fungus, being completely eliminated! Their research had been anticipated 24 years earlier in 1973 with the research involved in Patent No. 3,753,886. Not surprisingly though, due to the stranglehold, that the Pharmaceutical Cartel has in the U.S., this revolutionary clinical data was almost totally suppressed. Other than a few News Articles such as the Science News: Mar. 30, `91 pg. 207, Longevity: Dec. `92/pg. 14, and Houston Post: Mar. 20, '91 /Sect. A-10, plus the Patent No. 5,188,738,
Abstract ~ A method and system for the treatment of blood and/or other body fluids (such as amniotic fluids) as well as synthetic fluids such as tissue culture medium whereby a fluid to be treated is mechanically filtered for elimination of particles contained therein which exceed 0.2 microns in size (or some other minutely small size) and in addition subjecting the fluid being treated to electric field forces in the microwatt/milliwatt region induced by relatively low voltage of a few volts and low current density which does not exceed values which could impair the biological usefulness and characteristics of the blood or other fluid being treated.
There's been much controversy concerning embryonic stem cell research in recent years. However, a new study finds some patients are benefitting from ADULT stem cell therapy right now, and doctors hope we are one step closer to some major breakthroughs... Dr. Sean Kenniff reports... Donald Reid is hoping adult stem cells will give him more time. (Donald Reid/Heart Patient) THERE'S NOT MANY OPTIONS LEFT FOR ME. The 57-year-old has clogged arteries and heart disease so bad he's not a candidate for surgery. Instead he's joined an experimental study that involves this machine. It's taking his blood and pulling out stem cells. We're not talking about stem cells from an embryo. These are Donald's own adult stem cells. In the coming days doctors will inject them directly into Donald's heart… with the hope it will regenerate and revitalize the damaged organ. (Dr. Sean Kenniff/CBS NEWS) Adult stem cells have become standard therapy for treating several types of cancers like lukemia and lymphoma. But according to new research this treatment is now starting to show real promise in treating other diseases. A review of hundreds of trials found in some patients adult stem cells have stopped auto-immune diseases like rheumatoid arthritis and multiple sclerosis. Some heart patients like Donald have also seen improvement. Weill Cornell's Michael Schuster is excited by the results but warns it's still early. (Dr. Michael Schuster/NY Pres., Weill Cornell Med. Ctr.) WE DON'T KNOW YET WHAT THE BEST TECHNIQUE IS, WE DON'T REALLY KNOW HOW MUCH OF A BENEFIT THE PATIENTS WILL HAVE. And when it comes to diseases like Diabetes, Alzheimer's and Parkison's. (Dr. Michael Schuster/NY Pres., Weill Cornell Med. Ctr.) I THINK WE'RE STILL A FEW YEARS AWAY FROM KNOWING WHETHER STEM CELLS REALLY TURN OUT TO BE THE ANSWER. Donald should have an answer much sooner. His wish….. (Donald Reid/Heart Patient) TO BE LIKE EVERYONE ELSE AND NOT HAVE TO WORRY ABOUT THAT MY HEART MIGHT GIVE OUT. In the coming weeks he'll know if that wish came true
A Healthy Brain The healthy brain is made up of millions of interconnecting nerve cells, called neurons. Neurons constantly communicate with each other by sending signals through tentacle-like connections called axons and dendrites. How Alzheimer's Disease Affects the Brain The brain of a patient with Alzheimer's disease is much different. The orderly, organized arrangement of nerve cells found in a healthy brain become entangled, full of senile plaques and neurofibrillary tangles. The plaques and tangles interfere with the normal activity between neurons in the area of the brain responsible for intellectual thought. Symptoms of Alzheimer's Disease Alzheimer's disease affects people in different ways. The disease is slowly progressive from onset. Memory loss, confusion, disorientation, and poor judgment are a few of the symptoms of Alzheimer's disease.
Since innovation is “not necessarily always predictable,” Daniel Vasella declines to discuss it in a systematic way, and instead, focuses on a case study of one of his company’s flagship pharmaceuticals, Gleevec. The discovery, development and marketing of this drug, which fights the rare chronic myeloid leukemia (CML), may point to some of the things Novartis does right, suggests Vasella.
Many significant drugs result from years of basic research that takes place outside of industry. Pathbreaking work that occurred decades ago uncovered chromosome damage in patients with CML, and revealed an abnormal protein secreted due to this mutation. In the early 1990s, Novartis began the creative work of trying to block the signal of this cancer-causing protein.
After testing numerous compounds, Gleevec was synthesized in 1992, and “then the problems started,” says Vasella. When the drug was delivered intravenously, there were toxic effects, and they couldn’t reproduce results from cell cultures. With 100 researchers laboring on the problem, recounts Vasella, “marketing said, ‘stop this damn thing.’”
Despite the setbacks, “We persisted,” says Vasella. Indeed, the first clinical human trials, on 31 patients, were so spectacular -- 100% remission rates -- that Vasella didn’t believe the data. The company moved into frenetic pitch to complete the additional clinical trials necessary for FDA approval, and then on to production. Employees volunteered to work in 24-hour shifts, seven days a week. Vasella faced another issue: “We had to come up with a way we’d make money,” since CML affected a relative handful of patients globally. And the fewer the patients, the higher the price of the drug, potentially keeping it out of the hands of those who most needed it. The company decided to subsidize the cost of Gleevec for patients of little means. In spite of this, Gleevec “has surpassed all expectations.” Sales this year alone will exceed $2.4 billion.
What elements might have led to this triumph and Novartis’ more recent successes? Vasella cites “intrinsic motivation” in each Novartis staff member, high standards, savvy risk-taking and persistence in both research and marketing, and a company culture that brings out the best in everyone.
About the Speaker
Daniel Vasella
Chairman and CEO, Novartis
Daniel Vasella, M.D., was appointed Chairman in April 1999, having served as CEO and Head of the Group Executive Committee since the merger that created Novartis in 1996. Previously, Dr. Vasella was CEO of Sandoz Pharma Ltd. and a member of the Sandoz Group Executive Committee.
As CEO, Vasella created the Novartis Institute for BioMedical Research and moved the company’s research headquarters to Cambridge, Massachusetts, to be closer to top scientific talent as well as patient and hospital networks. He also established The Genomics Institute of the Novartis Research Foundation, which is focused on developing therapeutics from the data generated from the mapping of the human genome.
Vasella has implemented pioneering initiatives to ensure access to medicines, which include the founding of the Novartis Institute for Tropical Diseases for research on neglected diseases of the developing world, and the International Patient Assistance Program for the breakthrough cancer drug Gleevec®/Glivec™, an agreement to supply the novel malaria treatment Coartem® at cost to the World Health Organization and a pledge to donate the drug therapy needed to eradicate leprosy worldwide.
In 2003, Vasella was awarded The CancerCare Human Services Award and also the Harvard Business School’s Alumni Achievement Award. He holds the rank of Chevalier in the Ordre National de la Légion d’Honneur (France). Vasella is a member of the Board of Directors of PepsiCo, Inc., United States. In addition, he is a member of the Board of Dean’s Advisors at the Harvard Business School. He is also President of the International Federation of Pharmaceutical Manufacturers Associations.
About the Speaker
Daniel Vasella
Chairman and CEO, Novartis
Daniel Vasella, M.D., was appointed Chairman in April 1999, having served as CEO and Head of the Group Executive Committee since the merger that created Novartis in 1996. Previously, Dr. Vasella was CEO of Sandoz Pharma Ltd. and a member of the Sandoz Group Executive Committee.
As CEO, Vasella created the Novartis Institute for BioMedical Research and moved the company’s research headquarters to Cambridge, Massachusetts, to be closer to top scientific talent as well as patient and hospital networks. He also established The Genomics Institute of the Novartis Research Foundation, which is focused on developing therapeutics from the data generated from the mapping of the human genome.
Vasella has implemented pioneering initiatives to ensure access to medicines, which include the founding of the Novartis Institute for Tropical Diseases for research on neglected diseases of the developing world, and the International Patient Assistance Program for the breakthrough cancer drug Gleevec®/Glivec™, an agreement to supply the novel malaria treatment Coartem® at cost to the World Health Organization and a pledge to donate the drug therapy needed to eradicate leprosy worldwide.
In 2003, Vasella was awarded The CancerCare Human Services Award and also the Harvard Business School’s Alumni Achievement Award. He holds the rank of Chevalier in the Ordre National de la Légion d’Honneur (France). Vasella is a member of the Board of Directors of PepsiCo, Inc., United States. In addition, he is a member of the Board of Dean’s Advisors at the Harvard Business School. He is also President of the International Federation of Pharmaceutical Manufacturers Associations.
When Fiona Murray visited research centers in China recently, scientists greeted her quizzically: “People were baffled about what a business school professor was doing in stem cell and gene sequencing labs,” Murray says.
As it turns out, Murray’s tour was integral to her own MIT Sloan research exploring how science serves as a source of competitive advantage. As China and India and other developing countries produce scientists and engineers at a quickening pace, Murray hopes to find out if their capacity to capitalize on scientific ideas is expanding in a comparable way.
One challenge to this kind of research, says Murray, is that the market for scientific ideas “is poorly functioning.” Traditional markets, say for pork bellies, oil or diamonds have well-defined products, well-established metrics,” but how do you measure the quality of scientific ideas?
Murray’s solution is to visit key scientific and engineering institutes in other countries to observe both scientific infrastructure -- the physical state of laboratories -- and how researchers collaborate and generate useful knowledge. She also scans the scientific literature to see how many papers a particular country publishes, in what subdisciplines, and how many citations scientists receive.
Murray’s work may aid commercial enterprises intent on taking advantage of growing global scientific and engineering expertise. Some initial insights: places like China and India hold tremendous potential for firms, whether through their permissive regulatory climates or unique natural resources. But, she advises, don’t enter one of these countries expecting to hire scientists at bargain basement prices, since “the real costs of scientific labor are hidden.” Also, expect poor lab facilities, enormous bureaucracies and a crazy quilt of intellectual property and licensing rules.
Counsels Murray, “Start by collaborating on R&D with research institutes and labs. That allows you to understand their expertise, social rules of engagement and to potentially shape the rules.”
Synthetic biology is a new area of biological research that combines science and engineering in order to design and build ("synthesize") novel biological functions and systems
There’s no mistaking Drew Endy’s profession: “I like to make things -- that’s what I do.” From his engineer’s perspective, the slow and painful methods of bioengineering demand a solution. Endy hopes to refine the tools necessary to move the field forward. “We’re going from looking at the living world as only coming from nature, to a subset of the living world being produced by engineers who design and build hopefully useful living artifacts according to our specifications,” says Endy.
Thirty years ago, scientists figured out how to use enzymes to cut and paste genetic material, leading to recombinant DNA technology. But the techniques involved are painfully slow, requiring very specific physical materials and “know-how via the guild-like structure of biology.” Endy points to methods coming on line that will make it easier to design and build biological systems.
One is DNA synthesis, in which a machine fed information and sugars generates a physical piece of DNA. It reminds Endy of the “matter compilers” seen on Star Trek, where “food materializes from a cubby in the wall.” This technique will allow the economical production of long sequences of DNA. Another key ingredient in bioengineering will be the development of standards for making and measuring DNA, in the same way that machining hardware came to be governed by common standards in the 19th century. Endy also suggests that biotechnology will be increasingly informed by useful abstraction, so that scientists will manipulate raw materials less and refined and repackaged materials more, in order to make new things simply and more reliably. These advances will also enable bioengineers to “be experts in our own domains without having to be masters of everything.”
But as bioengineering becomes easier, and “people start to engineer biology,” we’ll need to worry about new issues, says Endy: Will people synthesize pathogens from scratch? Will groups pool knowledge legally? Will there be accreditation and oversight of those who create biological systems?
About the Speaker
Andrew Endy
Cabot Assistant Professor of Biological Engineering
Drew Endy earned degrees in civil, environmental, and biochemical engineering at Lehigh and Dartmouth. He studied genetics & microbiology as a postdoc at U.T. Austin and U.W. Madison. From 1998 through 2001 he helped to start the Molecular Sciences Institute, an independent not-for-profit biological research lab in Berkeley, CA.
In 2002, Endy started a group as a fellow in the Department of Biology and the Biological Engineering Division at MIT. He joined the MIT faculty in 2004. Endy co-founded the MIT Synthetic Biology working group and the Registry of Standard Biological Parts, and organized the First International Conference on Synthetic Biology. With colleagues he taught the 2003 and 2004 MIT Synthetic Biology labs that led to the organization of iGEM, the international Genetically Engineered Machine competiton.
In 2004 Endy co-founded Codon Devices, Inc., a venture-funded startup that is working to develop next-generation DNA synthesis technology. In 2005 Endy co-founded the BioBricks Foundation, a not-for-profit organization that is working to develop legal and economic strategies needed to support open biotechnology.
How do we distinguish our friends from foes? How does dementia destroy memory? And how can past experience invade the present with destructive force? Scientists are closing in on the biochemical roots of these neurological puzzles.
Thomas Insel describes the profound impact of a small group of neuropeptides on social behavior in animals, from worms to humans. Oxytocin, the hormone which turns on maternal behavior and cognition, turns out to play a large role in determining social memories. Mice whose genes for producing oxytocin are knocked out can’t seem to remember animals they’ve met 30 minutes earlier – what Insel describes as “dense social amnesia.” An area of the brain’s amygdala is particularly rich in oxytocin receptors, and when the peptide is injected into a nearby ventricle, the animals’ social interactions revert more closely to normal behavior. Oxytocin is a useful tool for interrogating the circuitry that enables humans to determine “who’s important to me, who I’d die for, who I’m pair-bonded with, who will take care of me,” says Insel.
Alzheimer’s Disease (AD), which afflicts 20 million people worldwide, begins by literally clogging and tangling the hippocampus, the part of the brain essential for learning and memory. Li-Huei Tsai and other researchers have found “compelling evidence” that a small protein may be critically important in activating AD’s awful atrophy of memory. By manipulating specific enzymes, Tsai has managed to model in animals “all the pathological hallmarks of Alzheimer’s Disease,” and zero in on the source of the plaques and tangles seen in human Alzheimer’s patients. Tsai foresees drug interventions that inhibit these enzymes. But, she says, a big task remains “even after we’re successful in halting a deleterious process--how can we restore learning and retrieve lost memory in AD patients?”
Why is it that only some people exposed to a shocking event develop post-traumatic stress disorder (PTSD)? Kerry Ressler’s research posits that some kind of learning must take place in the brain’s amygdala -- its fear response center—that cannot readily be extinguished. Researchers have tracked down a molecular factor that increases “after learning of fear or extinction of fear.” He believes that if this molecule is somehow blocked from doing its job, then someone suffering from PTSD cannot extinguish fear. In a fortuitous medical convergence, the drug D-cycloserine, which has been approved for years to treat tuberculosis, proves very effective in enhancing the effects of the molecule, and reducing fear of all kinds. One example: When people with fear of heights were given D-cycloserine as they took rides in elevators, they reported a significant, long-lasting reduction in their phobias.
Dr. Langer received the 2002 Charles Stark Draper Prize for inventing medical drug delivery technologies that prolong lives and ease suffering for millions every year.
Robert Langer has more than 500 issued or pending patents worldwide. In 2005, Langer received the $500,000 Albany Medical Center Prize in Medicine and Biomedical Research, America's top prize in medicine. In 2002, he received the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers, from the National Academy of Engineering. Among numerous other awards Langer has received are the Heinz Award for Technology, Economy and Employment (2003), the John Fritz Award (2003) (given previously to inventors such as Thomas Edison and Orville Wright) and the General Motors Kettering Award for Cancer Research (2004). Langer is one of very few people ever elected to all three U.S. National Academies and the youngest in history (age 43) ever to receive this distinction.
He received his Bachelor’s Degree from Cornell University in 1970 and his Sc.D. from the Massachusetts Institute of Technology in 1974, both in Chemical Engineering.
Tyler Jacks introduces the key research areas and scientists who will speak in the succeeding sessions. He offers a thumbnail sketch of cancer as a molecular genetic progression involving sequential alterations in, and the proliferation of, abnormal cells. “Think of a cancer cell like an integrated circuit: the same kinds of complexities in electronic networks also exist within cells,” notes Jacks. Because of work on the human genome, and advances in scientists’ ability to untangle these complex molecular interactions, “We now have the first generation of anti-cancer drugs targeted against molecular alterations in cancer,” says Jacks. Two highly successful drugs have already been derived from MIT research.
In addition, says Jacks, collaboration among biologists, engineers and mathematicians are yielding “a tremendous collection of tools and technologies.” These include tiny probes that enable diagnosis of cancers at earlier stages, nanoparticles that deliver a therapeutic payload directly to cancer cells, and devices that can be implanted in the body.
In Doug Lauffenburger’s view, MIT’s new bioengineering degree program is not merely justified, it is essential. Revolutionary changes in biological sciences—specifically, in molecular biology and genomics—have given scientists the means to understand and control both the building blocks and larger systems of living things. Now, says Lauffenburger, the “operation of biological functions needs to be understood in terms of biomolecular machines.” But the hard part, he says, is “predicting what happens when you manipulate them. It’s almost trial and error. That’s where engineering comes in.”
Linda Griffith provides one paradigm for such research. She is designing a scaffold on which to grow human cells for use in tissue implants. Using a “computer controlled process that builds complex 3D objects up from scratch,” Griffith creates a device that mimics the complex structures of joints and other body parts – suited for joint repair, or bone regeneration. Her research might someday produce organs for transplant. But Griffith’s grander goal involves “putting surgeons out of business,” by eliminating transplants altogether. She’s building a “liver on a chip” – growing liver cells on a tiny wafer with the architecture and molecular properties of actual liver cells. This biomechanical product can be used to test drug toxicity and gene therapies, and perhaps someday to model and block the growth of cancers.
Angela Belcher models her bioengineered devices on some of nature’s most ingenious products, such as the incredibly strong and exquisitely structured abalone shell. She designs on a nanoscale, getting viruses and antibodies to work with inorganic materials. “How far can you push organisms?” Belcher wonders. To date, she’s taught a nontoxic virus to recognize a specific metal used in a semiconductor wafer. Someday viruses could detect atomic defects in electronics. Belcher also describes virus scaffolds for growing semiconductor wires, and for generating lightweight batteries woven into soldier’s uniforms. She’s even looking into ways of spinning viruses, as spiders spin silk, for generating optical materials.
Rudolf Jaenisch quietly insists, and instead look closely at the biology involved. First, note that there are two different kinds of cloning: reproductive cloning, the attempt to create an exact replica of a human being, which Jaenisch believes to be both biologically flawed and morally questionable; and therapeutic cloning, which offers potential cures to some of mankind’s most devastating diseases, and from Jaenisch’s point of view, sidesteps ethical pitfalls. Both involve transferring the genetic material from a somatic cell (from the skin, for instance) into an individual egg cell. The fertilized cell gives rise to embryonic stem cells, which have the near miraculous capacity to differentiate into every kind of tissue found in the body. Jaenisch says human embryonic stem cell research could help reveal the mechanisms behind biological growth, and enable a customized approach to treating such diseases as diabetes and Parkinson’s. Once scientists create these ES cells, they can grow them in vitro.
Ethical problems emerge, Jaenisch believes, when a cloned embryo is implanted in a uterus with the intent of creating a full-term clone, or with the intent of harvesting stem cells from an aborted fetus. These involve the “destruction of potential life.” The creation of cloned ES cells for research purposes, however, is the “propagation of existing life,” says Jaenisch.
Stephen Marks delineates the various human rights arguments around cloning: Are we at risk “of turning people into products?” Can “we pursue genetic health and enhancements” while maintaining the individual’s dignity? He describes the U.S. administration’s current opposition to any form of cloning and in particular, its attempt to throttle international treaties that might eventually permit therapeutic cloning.
About the Speakers
Rudolf Jaenisch
Professor of Biology, MIT Founding Member, Whitehead Institute for Biomedical Research
Jaenisch is one of the founders of transgenic science (gene transfer to create mouse models of human disease). His lab has produced mouse models leading to new understanding of cancers and various neurological diseases.
He received his doctorate in medicine from the University of Munich in 1967. He came to the Whitehead from the University of Hamburg in Germany, where he was head of the Department of Tumor Virology at the Heinrich Pette Institute.
Jaenisch received the 2002 Robert Koch Prize for Excellence in Scientific Achievement. In 2003, he was awarded the Charles Rodolphe Brupbacher Prize for basic research in oncology and was elected a member of the National Academy of Sciences.
Jaenisch is a fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology, and a member of the American Association for the Advancement of Science.
Stephen P. Marks
François-Xavier Bagnoud Professor of Health and Human Rights Department of Population and International Health
Harvard School of Public Health
Stephen Marks' current interests include integrating human rights into sustainable human development. He has been a consultant to the United Nations Development Program on this topic and is principal investigator for a major grant by the Government of the Netherlands on the right to development. Another current research interest is international efforts to limit human genetic manipulation, focusing on human reproductive cloning and germline gene therapy. This study explores the human rights implications of these techniques and the assumptions of opposing attitudes on this question. Among his many degrees, he holds a Doctor of Laws (Docteur d’Etat en droit), with high honors, Institute of the Law of Peace and Development, Faculty of Law and Economics, University of Nice, 1979; an advanced degree (Diplôme d’études appliqués avancées, DEAA) in administrative litigation and human rights, Faculty of Law, Economics and Political Science of the University of Besançon, 1977; and a Certificate of European Studies, Institute of Advanced European Studies of the University of Legal, Political and Social Sciences of Strasbourg, 1972.
If the future once lay in plastics, as the film “The Graduate” claimed, today the watchword may be “feedstocks.” This term includes corn, wheat, soy, sunflower, rapeseed (canola)—the array of carbohydrates and proteins growing in fields across the planet. The news, as Douglas Cameron makes clear, is that these crops no longer serve just as staples for animal and human diets, but as the basis for a “revolution in the chemical industry.” Cameron’s company, Cargill, is exploring a host of biotech applications for carbohydrates, fats and proteins found in common crops. For instance, they’re attempting to convert a plastic derivative of lactic acid (derived from fermented starch) into inexpensive polymers for medical implants. Another application: polylactide fibers that not only give comfort to clothing but provide high wicking power. Cameron also sees soy and vegetable oils as a promising industrial “platform.” Cargill envisions transforming them for use in engines, as lubricants, hydraulic and transformer fluids, replacing environmentally unfriendly chemicals. If industry can find effective conversion methods, grains and legumes may emerge as primary sources of fuel, key ingredients in drugs and diet supplements, clothing and paper products, and as heightened versions of themselves—more nutritious food for people and animals.
Douglas C. Cameron PhD '87
Director of Biotechnology Biotechnology Development Center Cargill, Inc.
Douglas C. Cameron leads molecular biology and metabolic engineering research and development at Cargill. From 1986-1998, Cameron was a professor in the Department of Chemical Engineering and an affiliate in the Molecular Biology Program at the University of Wisconsin-Madison. In 1996 he was a guest professor in the Institute for Biotechnology at the ETH in Zurich, Switzerland. From 1979-1981 Cameron held the position of Biochemical Engineer at Advanced Harvesting Systems, a plant biotechnology company funded by International Harvester. Cameron is a Fellow of the American Institute of Medical and Biological Engineering (AIMBE). He is on the editorial boards of Metabolic Engineering and Biomacromolecules. Cameron serves on the Minnesota Governor's Bioscience Council and the board of directors of Minnesota Biotechnology Industry Organization. He is a member of the MIT Biological Engineering visiting committee and on the managing board of the newly formed Society for Biological Engineering. Cameron is also a Consulting Professor in the Department of Chemical Engineering at Stanford University. He has a B.S.E. in biomedical engineering in 1979 from Duke University, and a Ph.D. in biochemical engineering in 1986 from MIT
