Science Weekly podcast: Just how many universes are there?

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Brian Greene claims that every decision we make creates a parallel universe – and the proof is in the maths; plus, we join Tim Jackson as he takes a Q&A session on whether rampant consumerism is ruining our lives

ILSI Biomed Israel 2011



Dr. Mitchel, President of Target Health will again be attending the ILSI-Biomed 2011 Conference will be held on May 23-25, 2011 in Tel-Aviv. Please let us know if you are attending.


The conference is a meeting place for industry and academia from Israel and abroad. International visitors come to hear about and witness the various innovations, and experience first-hand the Israeli entrepreneurial spirit. In 2011, Biomed will celebrate the conference’s 10th anniversary. Last year’s event drew 6,000 industry players, engineers and scientists, with 1,000 participants from 42 countries and in excess of 2,500 one-on-one meetings.


This year’s conference will feature a rich program and supporting events:


*       A full day Cardiovascular Symposium and seminars focusing on the patient of tomorrow, preventative medicine, oncology, orphan diseases, CNS diseases, and regulation/reimbursement

*       60 presentations given by Israeli medical device and biopharma companies

*       Cutting-edge keynote addresses by prominent industry leaders from Israel and abroad

*       A platform where science, technology, academia and industry come together

*       Present up-to-date issues around the economical and regulatory landscape and the future of healthcare through a variety of panels on industry topics and trends

*       Provide a meeting place for personalized one-on-one meetings and networking opportunities

*       Start-up Pavilion where a wealth of innovation is displayed


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

Personlized Dendritic Cell Vaccine Increases Survival in Patients with Deadly Brain Cancer

A dendritic cell vaccine personalized for each individual based on the patient’s own tumor may increase median survival time in those with a deadly form of brain cancer called 1) ___. Published in Clinical Cancer Research (2010;17:1603), the study also identified a subset of patients with mesenchymal glioblastoma who were more likely to respond to the vaccine. Mesenchymal glioblastoma accounts for about one-third of all cases of glioblastoma.


This is the first time in brain 2) ___ that a subset of patients more likely to respond to an immunotherapy has been identified, said Dr. Linda Liau, a Jonsson Cancer Center researcher, professor of neurosurgery and senior author of the study.


The study found that the vaccine, administered after the conventional treatments of surgery and radio-chemotherapy, was associated with a median survival of 31.4 months, double the 15 months of historical controls. In all, 23 patients were enrolled in the Phase I study that was launched in 2003. Of those, about one third of participants are still alive, some more than eight years after their 3) ___. The study also found that side effects were minimal, limited mostly to flu-like symptoms and rashes near the vaccine 4) ___ site.


“This is quite an encouraging result, especially in an early phase study like this,” Liau said. “It’s promising to see patients with this type of brain cancer experience such long 5) ___.” However, Liau cautioned that the findings need to be confirmed in larger, randomized studies. A Phase II, randomized study at UCLA is underway testing the vaccine in newly diagnosed glioblastoma patients. For the study, patients will receive either the standard of care (surgery, radiation and 6) ___) or the standard of care plus the vaccine.


It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative and mesenchymal. During the course of her study, Liau and her colleagues observed that one group of patients seemed to be responding very well to the vaccine and examined their tumors using a microarray analysis of their DNA. They found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the 7) ___. The finding was surprising because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival than those with the other subtypes. In patients with this type of glioblastoma, several 8) ___ that modulate the immune system are dysregulated, meaning they don’t work properly. The authors speculate that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.

“Glioblastoma remains one of the diseases for which there is no curative therapy … and the prognosis for patients with primary malignant brain 9) ___ remains dismal,” the study states.


Brad Silver, 41, who grew up in Southern California and now lives in a Cleveland suburb, was diagnosed with glioblastoma in 2003 and was told that he had, at best, two months to live. Silver sought a second opinion at UCLA and the golf-ball sized tumor in his left lateral lobe was removed. He underwent radiation and chemotherapy and enrolled in the vaccine 10) ___ trial.


The vaccine preparation is 11) ___ for each individual. After the tumor is removed, tumor proteins are extracted which provide the antigens for the vaccine to target. After radiation and chemotherapy, the white blood cells are taken from the patient and grown into dendritic cells, a type of white blood cell that is an antigen-presenting cell. The vaccine preparation from this point takes about two weeks, as the 12) ___ cells are grown together with the patient’s own tumor antigens. The tumor-pulsed dendritic cells are then injected back in to the body, prompting the T cells to go after the tumor proteins and fight the malignant cells. The dendritic cells apparently activate the patient’s T cells to attack the tumor, basically teaching the 13) ___ system to respond to the tumor. The individualized vaccine is injected into the patient in three shots given every two weeks for a total of six weeks. Booster shots are given once every three months until the cancer recurs. Patients are scanned every two months to monitor for 14) ___ recurrence.


ANSWERS: 1) glioblastoma; 2) cancer; 3) diagnosis; 4) injection; 5) survivals; 6) chemotherapy; 7) vaccine; 8) genes; 9) tumors; 10) clinical; 11) personalized; 12) dendritic; 13) immune; 14) disease

Solving the Puzzle of Henry VIII


Blood group incompatibility between Henry VIII and his wives could have driven the Tudor king’s reproductive woes. In addition, a genetic condition related to his suspected blood group could also explain Henry’s dramatic mid-life transformation into a physically and mentally-impaired tyrant who executed two of his wives. Research conducted by bioarchaeologist Catrina Banks Whitley while she was a graduate student at SMU (Southern Methodist University) and anthropologist Kyra Kramer shows that the numerous miscarriages suffered by Henry’s wives could be explained if the king’s blood carried the Kell antigen. A Kell negative woman who has multiple pregnancies with a Kell positive man can produce a healthy, Kell positive child in a first pregnancy. However, the antibodies she produces during that first pregnancy will cross the placenta and attack a Kell positive fetus in subsequent pregnancies.


As published in The Historical Journal (2010;53), the pattern of Kell blood group incompatibility is consistent with the pregnancies of Henry’s first two wives, Katherine of Aragon and Anne Boleyn. If Henry also suffered from McLeod syndrome, a genetic disorder specific to the Kell blood group, it would finally provide an explanation for his shift in both physical form and personality from a strong, athletic, generous individual in his first 40 years to the monstrous paranoiac he would become, virtually immobilized by massive weight gain and leg ailments.


Henry married six women, two of whom he famously executed, and broke England’s ties with the Catholic Church, all in pursuit of a marital union that would produce a male heir. Historians have long debated theories of illness and injury that might explain the physical deterioration and frightening, tyrannical behavior that he began to display after his 40th birthday. Less attention has been given to the unsuccessful pregnancies of his wives in an age of primitive medical care and poor nutrition and hygiene.


Further supporting the Kell theory, descriptions of Henry in mid-to-late life indicate he suffered many of the physical and cognitive symptoms associated with McLeod syndrome – a medical condition that can occur in members of the Kell positive blood group. By middle age, the King suffered from chronic leg ulcers, fueling longstanding historical speculation that he suffered from type II diabetes. The ulcers also could have been caused by osteomyelitis, a chronic bone infection that would have made walking extremely painful. In the last years of his life, Henry’s mobility had deteriorated to the point that he was carried about in a chair with poles. That immobility is consistent with a known McLeod syndrome case in which a patient began to notice weakness in his right leg when he was 37, and atrophy in both his legs by age 47.


The Tudor king could have been suffering from medical conditions such as these in combination with McLeod syndrome, aggravated by his obesity. Records do not indicate whether Henry displayed other physical signs of McLeod syndrome, such as sustained muscle contractions (tics, cramps or spasms) or an abnormal increase in muscle activity such as twitching or hyperactivity. McLeod syndrome resembles Huntington’s disease, which affects muscle coordination and causes cognitive disorder. McLeod symptoms usually begin to develop when an individual is between 30 and 40 years old, often resulting in damage to the heart muscle, muscular disease, psychiatric abnormality and motor nerve damage. Henry VIII experienced most, if not all, of these symptoms.

Higher Cancer Risk Continues After Chernobyl

According to an article published online in the journal Environmental Health Perspectives (17 March 2011), nearly 25 years after the accident at the Chernobyl nuclear power plant in Ukraine, exposure to radioactive iodine-131 from the fallout may be responsible for thyroid cancers that are still occurring in those who were children or adolescents at the time of the accident. An international team of researchers led by the National Cancer Institute (NCI), found a clear dose-response relationship, in which higher absorption of radiation led to an increased risk for thyroid cancer that has not seemed to diminish over time.


The study included over 12,500 participants who were under 18 years of age at the time of the Chernobyl accident on April 26, 1986, and lived in one of three Ukrainian oblasts, or provinces, near the accident site: Chernigov, Zhytomyr, and Kiev. Thyroid radioactivity levels were measured for each participant within two months of the accident and were used to estimate each individual’s I-131 dose. The participants were screened for thyroid cancer up to four times over 10 years, with the first screening occurring 12 to 14 years after the accident.


Standard screenings included feeling for growths in the thyroid glands and an ultrasonographic examination (a procedure that uses sound waves to image the thyroid gland within the body), and an independent clinical examination and thyroid exam by an endocrinologist. Participants were asked to complete a series of questionnaires including items specifically relevant to thyroid dose estimation. These items included residential history, milk consumption, and whether they were given preventive doses of non-radioactive iodine in the two months following the accident, to help lessen the amount of radioactive iodine that would be absorbed by the thyroid. Participants with a suspected thyroid cancer were referred for a biopsy to collect potentially cancerous cells for microscopic examination. If warranted, participants were also referred for surgery. In total, 65 of the study participants were diagnosed with thyroid cancer.


The study found no evidence, during the study time period, to indicate that the increased cancer risk to those who lived in the area at the time of the accident is decreasing over time. However, a separate, previous analysis of atomic bomb survivors and medically irradiated individuals found cancer risk began to decline about 30 years after exposure, but was still elevated 40 years later. The authors believe that continued follow-up of the participants in the current study will be necessary to determine when an eventual decline in risk is likely to occur.

Radiation Risks Resulting From the Japanese Nuclear Accident

Radiation Risks to Health: A Joint Statement from Leading Scientific Experts

Any radiation that’s released would travel primarily east and northeast across the Pacific Ocean, eventually reaching North America somewhere between Alaska and California. However, because of the huge distance traveled at approximately 10 miles/hr., any harmful radiation would likely be dispersed into the atmosphere before reaching U.S. shores 7-11 days later.


The growing concern surrounding the release of radiation from an earthquake and tsunami-stricken nuclear complex in Japan has raised fears of radiation exposure to populations in North America from the potential plume of radioactivity crossing the Pacific Ocean. To help Americans understand their radiation-related health risks, the American Association of Clinical Endocrinologists (AACE), the American Thyroid Association (ATA), The Endocrine Society and the Society of Nuclear Medicine (SNM) issued a joint statement on March 21, 2011.


The statement suggests that the principal radiation source of concern, in regard to impact on health, is radioactive iodine including iodine-131.This presents a special risk to health because exposure of the thyroid to high levels may lead to development of thyroid nodules and thyroid cancer years later. Radioactive iodine uptake to the thyroid can be blocked by taking potassium iodide (KI) pills. However the statement cautions KI should not be taken unless there is a clear risk of exposure to high levels of radioactive iodine. While some radiation may be detected in the United States as a result of the nuclear reactor accident in Japan, current estimates indicate radiation levels will not be harmful to the thyroid gland or general health. If radiation levels did warrant the use of KI, the statement recommends it should be taken as directed by physicians or public health authorities until the risk for significant exposure dissipates.


Since there is not a radiation emergency in the United States or its territories, the statement does not support the ingestion of KI prophylaxis at this time. KI can cause allergic reactions, skin rashes, salivary gland inflammation, hyperthyroidism or hypothyroidism in a small percentage of people.


Several kinds of radioactive elements that can be released by a nuclear meltdown have the potential to cause cancer.


*       Iodine-131: The thyroid gland takes up iodine from the blood to make critical hormones. People exposed to radioactive iodine can develop cancer if this version ends up in their thyroids. Taking a stable form of iodine, potassium iodide, helps fill up the thyroid, keeping the radioactive iodine out. Potassium iodide doesn’t protect other organs.


*       Cesium-137: This element, which can dissolve in groundwater, goes to the bone, where it also can cause bone cancer and leukemia, which affects blood cells made in the bone marrow.


*       Strontium-90: This element acts like calcium, also building up in bones and teeth, also causing bone cancer and leukemia.


*       Plutonium-241: This element can accumulate in the bone and liver, causing cancer.


Finding of Long-Sought Drug Target Structure May Expedite Drug Discovery

According to an article published online in Science Express (10 March 2011), .The three-dimensional structure of a key biological receptor has been revealed. The finding has the potential to speed drug discovery in many areas, from arthritis to respiratory disorders to wound healing, because it enables chemists to better examine and design molecules for use in experimental drugs.


“This is an important step forward – it was impossible until recently to know how this type of receptor is switched on by chemical signals like a tiny machine,” said Dr. Kenneth A. Jacobson, chief of the Laboratory of Bioorganic Chemistry in NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and an author on the paper. “The architecture of the activated receptor allows us to think in more detailed terms about the other half of the drug interaction. We hope that we’re on the verge of a revolution that will expedite the process of crafting new drugs to treat disease.”


A receptor is a protein that receives and sends signals to other molecules. The three-dimensional structure of the solved receptor also contains an agonist – a chemical command signal from outside the cell – in this case, an adenosine molecule. Similar to the function of a telephone receiver, the receptor acts as a sensor, picking up the message from the agonist and transmitting its information, which begins processes inside the cell.


The authors discovered that a previously known agonist molecule would bind to its receptor target in a way that stabilizes the protein for crystallization. Once crystallized, the structure can be seen by bombarding it with X-rays. The agonist solidifies the protein by connecting to multiple parts of the receptor with its molecular arms, in the process initiating the function of the entire structure. This adenosine receptor, called A2A, counteracts inflammation and responds to organs in distress. It belongs to the G-protein coupled receptor family, which is involved in processes necessary for many drugs currently in use to take effect.

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FDA, EMA Announce Pilot for Parallel Assessment of Quality by Design Applications



The FDA and EMA have launched a new pilot program that will allow parallel evaluation of relevant development and manufacturing data components, known as Quality by Design (QbD), of new drug marketing applications that are submitted to both agencies. The parallel evaluation within this voluntary pilot program means that reviewers from both agencies will separately assess the quality/chemistry, manufacturing and control (CMC) section of the new drug applications (NDAs) submitted to the FDA and marketing authorization applications (MAAs) submitted to the EMA. However, there will be regular communication and consultation between European regulators and their U.S. colleagues throughout the review process relevant to QbD aspects of the applications.


QbD in pharmaceuticals involves designing and developing pharmaceutical formulations and manufacturing processes to help ensure product manufacturing quality. Several guidelines have been developed by the International Conference on Harmonisation (ICH) to harmonize and facilitate the implementation of QbD. This pilot program began out of concern that certain ICH guidelines were being interpreted differently in Europe and the United States. Goals of the pilot program include:


1.      Helping to ensuring consistent implementation of ICH guidelines for manufacturing quality in the application evaluation process

2.      Increasing awareness of these regulatory concepts by staff that review marketing applications and inspect manufacturing facilities as part of the approval process

3.      Defining the reviewer and inspector interaction for QbD applications

4.      Creating a further way for EMA and FDA assessors/reviewers to share full knowledge about these applications

5.      Developing and harmonizing regulatory decisions to the greatest extent possible.


This pilot program applies to NDAs and MAAs, some supplements, and CMC meeting requests that include QbD elements submitted to both agencies at about the same time. The pilot will only include chemical entities and not biologically-derived products. Review of QbD applications does not change statutory deadlines. The pilot will end on March 31, 2014.


For more information:


For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.


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