[Source: ScienceDaily] - Sleep disruption is the most common and severe symptom reported by middle-aged women when their periods change and they start moving into the menopause, according to a study in the April issue of the UK-based Journal of Clinical Nursing.
Researchers at the University of Arizona College of Nursing, USA, spoke to 110 women entering menopause -- when periods can become lighter or heavier and occur at longer or shorter intervals. Their average age was 49 and they had all experienced their last menstrual period in the last three years.
On average, they reported suffering from seven of the ten most common menopause symptoms.
95% suffered from sleep difficulties, 92% from forgetfulness, 87% from irritability, 85% from night sweats and 91% from hot flashes or flushes.
The other symptoms reported were: mood swings (75%), depression (71%), day sweats (66%), vaginal dryness (55%) and irregular bleeding (35%).
Women taking part in the study were also asked to rate the severity of ten menopause symptoms on a scale of zero to four, where zero was no symptoms and four was extreme. The average severity score was 20.8 out of a possible 40.
Difficulty sleeping was the most severe symptom, scoring an average of 2.90 out of four, followed by night sweats (2.58), irritability (2.56), forgetfulness (2.42), hot flashes or flushes (2.41) and mood swings (2.12).
Women reported that they were less affected by day sweats (1.88), depression (1.73), vaginal dryness (1.45) and irregular bleeding (0.82).
"We also talked to the women about how frequently they experienced symptoms" says lead researcher and associate professor Dr Judith A Berg. "Women who reported problems with day sweats and hot flashes or flushes experienced an average of six a day and women who had problems with night sweats averaged just under three a night."
The average time since the women's last menstrual period (LMP) was five months and the cut off point for the study was 36 months since the last period. Women were included in the study if they had a minimum severity score of at least 12 out of 40 when they were asked to rate the ten key symptoms on a scale of zero to four.
Women who had health problems like diabetes or a history of breast or uterine cancer were excluded, as were women who were on certain types of medication, like hormone treatment or tranquilizers.
The researchers found that some menopausal symptoms changed in frequency as women moved further into the menopause. But sleep disturbance was a notable exception, remaining constant regardless of when a woman had had her LMP.
For example women who had had their LMP in the last two months experienced an average of 3.4 hot flashes or flushes a day and this more than doubled to 7.60 in women who had had their LMP in the last three to 11 months. By 12 months plus the level had fallen to 6.83.
The pattern was the same for day sweats, starting at 3.50 a day and rising to 5.97 before falling to 5.17.
However, night sweats rose consistently during this time, starting at 1.86, then rising to 2.67 and 3.25.
"This contradicts earlier research which sought to link sleep difficulties with night sweats and problems like hot flashes or flushes" stressed Dr Berg. "Although the severity of these problems changed as the women progressed through the early stage of the menopause, the sleep difficulties the women reported remained fairly constant."
The study also showed that, with the exception of sleep difficulties, the most common symptoms reported by the women were not necessarily the ones that they said were the most severe.
"For example, forgetfulness was the second most commonly reported symptom, but when it came to severity it only rated seventh out of the 10 symptoms studied" says Dr Berg.
"And night sweats were the fourth most common symptom, but women rated them second when it came to severity.
"These findings underline the importance of talking to women about the severity of symptoms and the distress they cause as well as how frequently they occur."
The researchers note that a number of previous studies have identified hot flashes or flushes as the biggest problem for menopausal women.
"Our study looked at women who were relatively young and the time lapse since their last period was shorter than in a number of previous studies" explains Dr Berg. "It is known that hot flashes or flushes increase as the menopause progresses and emerging data suggests that other symptoms are more severe in the earlier stages."
A woman is said to have reached the menopause when she has not had a period for a year. During this phase, known as the perimenopause, the hormonal and biological changes associated with the menopause begin and many women experience both physical and emotional symptoms.
"What our study clearly shows is that women who are entering the menopause find sleep difficulties a frequent and distressing problem and that this problem was consistently reported by women in the sample, regardless of when they had had their last period" concludes Dr Berg.
Journal reference: Menopausal symptom perception and severity: results from a screening questionnaire. Berg et al. Journal of Clinical Nursing. 17, pp 940 to 948. (April 2008).
Adapted from materials provided by Wiley-Blackwell, via EurekAlert!, a service of AAAS.
Tuesday, April 29, 2008
As Nanotechnology Goes Mainstream, 'Toxic Socks' Raise Concerns; Unknown Risks From Nanosilver Cited
[Source: ScienceDaily] - Nanotechnology is now available in a store near you. Valued for it's antibacterial and odor-fighting properties, nanoparticle silver is becoming the star attraction in a range of products from socks to bandages to washing machines. But as silver's benefits propel it to the forefront of consumer nanomaterials, scientists are recommending a closer examination of the unforeseen environmental and health consequences of nanosilver.
"The general public needs to be aware that there are unknown risks associated with the products they buy containing nanomaterials," researchers Paul Westerhoff and Troy M. Benn said in a report scheduled for the 235th national meeting of the American Chemical Society (ACS).
Westerhoff and Benn report that ordinary laundering can wash off substantial amounts of the nanosilver particles from socks impregnated with the material. The Arizona State researchers suggest that the particles, intended to prevent foot odor, could travel through a wastewater treatment system and enter natural waterways where they might have unwanted effects on aquatic organisms living in the water and possibly humans, too.
"This is the first report of anyone looking at the release of silver from this type of manufactured clothing product," said the authors.
Behind those concerns lies a very simple experiment. Benn and Westerhoff bought six pairs of name brand anti-odor socks impregnated with nanosilver. They soaked them in a jar of room temperature distilled water, shook the contents for an hour and tested the water for two types of silver -- the harmful "ionic" form and the less-studied nanoparticle variety.
"From what we saw, different socks released silver at different rates, suggesting that there may be a manufacturing process that will keep the silver in the socks better," said Benn. "Some of the sock materials released all of the silver in the first few washings, others gradually released it. Some didn't release any silver." The researchers will present the specific brands they studied at their ACS presentation.
If sufficient nanosilver leeches out of these socks and escapes waste water treatment systems into nearby lakes, rivers and streams, it could damage aquatic ecosystems, said Benn. Ionic silver, the dissolved form of the element, does not just attack odor-causing bacteria. It can also hijack chemical processes essential for life in other microbes and aquatic animals.
"If you start releasing ionic silver, it is detrimental to all aquatic biota. Once the silver ions get into the gills of fish, it's a pretty efficient killer," said Benn. Ionic silver is only toxic to humans at very high levels. The toxicity of nanoparticle silver, said Westerhoff, has yet to be determined.
Westerhoff and Benn did not intend to establish the toxicity of silver. "The history of silver and silver regulation has been set for decades by the U. S. Environmental Protection Agency -- we're not trying to reexamine or reinvent that," said Westerhoff.
They do hope to spark a broader examination of the environmental and health consequences of nanomaterials, as well as increasing awareness of nanotechnology's role in everyday consumer goods.
Silver has been used historically since ancient roman times, though its nanoparticle form has only recently appeared in consumer products. Beyond socks, nanosilver appears in certain bandages, athletic wear and cleaning products. Benn suggested that most consumers are unaware of these nano-additions.
"I've spoken with a lot of people who don't necessarily know what nanotechnology is but they are out there buying products with nanoparticles in them. If the public doesn't know the possible environmental disadvantages of using these nanomaterials, they cannot make an informed decision on why or why not to buy a product containing nanomaterials," said Benn.
To that end, the researchers suggest that improved product labeling could help. Westerhoff proposes that clothing labels could become like the back of a food packaging, complete with a list of "ingredients" like nanosilver.
Westerhoff and Benn expect to expand their leeching experiments to other consumer products imbued with nanomaterials. They hope to find the moment in each product's lifecycle when nanomaterials could be released into the environment, as well as developing better detection methods to characterize nanoparticles in water and air samples.
"Our work suggests that consumer groups need to start thinking about these things," said Benn. "Should there be other standards for these products?"
Adapted from materials provided by American Chemical Society, via EurekAlert!, a service of AAAS.
"The general public needs to be aware that there are unknown risks associated with the products they buy containing nanomaterials," researchers Paul Westerhoff and Troy M. Benn said in a report scheduled for the 235th national meeting of the American Chemical Society (ACS).
Westerhoff and Benn report that ordinary laundering can wash off substantial amounts of the nanosilver particles from socks impregnated with the material. The Arizona State researchers suggest that the particles, intended to prevent foot odor, could travel through a wastewater treatment system and enter natural waterways where they might have unwanted effects on aquatic organisms living in the water and possibly humans, too.
"This is the first report of anyone looking at the release of silver from this type of manufactured clothing product," said the authors.
Behind those concerns lies a very simple experiment. Benn and Westerhoff bought six pairs of name brand anti-odor socks impregnated with nanosilver. They soaked them in a jar of room temperature distilled water, shook the contents for an hour and tested the water for two types of silver -- the harmful "ionic" form and the less-studied nanoparticle variety.
"From what we saw, different socks released silver at different rates, suggesting that there may be a manufacturing process that will keep the silver in the socks better," said Benn. "Some of the sock materials released all of the silver in the first few washings, others gradually released it. Some didn't release any silver." The researchers will present the specific brands they studied at their ACS presentation.
If sufficient nanosilver leeches out of these socks and escapes waste water treatment systems into nearby lakes, rivers and streams, it could damage aquatic ecosystems, said Benn. Ionic silver, the dissolved form of the element, does not just attack odor-causing bacteria. It can also hijack chemical processes essential for life in other microbes and aquatic animals.
"If you start releasing ionic silver, it is detrimental to all aquatic biota. Once the silver ions get into the gills of fish, it's a pretty efficient killer," said Benn. Ionic silver is only toxic to humans at very high levels. The toxicity of nanoparticle silver, said Westerhoff, has yet to be determined.
Westerhoff and Benn did not intend to establish the toxicity of silver. "The history of silver and silver regulation has been set for decades by the U. S. Environmental Protection Agency -- we're not trying to reexamine or reinvent that," said Westerhoff.
They do hope to spark a broader examination of the environmental and health consequences of nanomaterials, as well as increasing awareness of nanotechnology's role in everyday consumer goods.
Silver has been used historically since ancient roman times, though its nanoparticle form has only recently appeared in consumer products. Beyond socks, nanosilver appears in certain bandages, athletic wear and cleaning products. Benn suggested that most consumers are unaware of these nano-additions.
"I've spoken with a lot of people who don't necessarily know what nanotechnology is but they are out there buying products with nanoparticles in them. If the public doesn't know the possible environmental disadvantages of using these nanomaterials, they cannot make an informed decision on why or why not to buy a product containing nanomaterials," said Benn.
To that end, the researchers suggest that improved product labeling could help. Westerhoff proposes that clothing labels could become like the back of a food packaging, complete with a list of "ingredients" like nanosilver.
Westerhoff and Benn expect to expand their leeching experiments to other consumer products imbued with nanomaterials. They hope to find the moment in each product's lifecycle when nanomaterials could be released into the environment, as well as developing better detection methods to characterize nanoparticles in water and air samples.
"Our work suggests that consumer groups need to start thinking about these things," said Benn. "Should there be other standards for these products?"
Adapted from materials provided by American Chemical Society, via EurekAlert!, a service of AAAS.
First Diagnostic Test For Alzheimer's And Parkinson's Disease On The Horizon
[Source:ScienceDaily] -A new blood test that can give an early diagnosis of neurodegenerative disease and distinguish between Parkinson's and Alzheimer's disease could be launched this summer, reports Marina Murphy in SCI's Chemistry & Industry magazine.
Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4."
"There is currently no diagnostic test for any neurodegenerative disease on the market -- diagnoses are currently based solely on a clinical diagnosis of symptoms," said chief executive, Steve Rash.
Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.
Although the test has been welcomed by Kieran Breen, director of research at the Parkinson's Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: "While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis."
Susan Sorensen, head of research at the UK Alzheimer's Society said: "There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer's disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.
"The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer's disease... Some suggest Alzheimer's, for example, is too complex to be identified in this way."
Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.
Note: (1) Expert Review of Proteomics 2008, 5(1), 1-8; Biochemical and Biophysical Research Communications 2006, 342, 1034-1039
Adapted from materials provided by Society of Chemical Industry, via EurekAlert!, a service of AAAS.
Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4."
"There is currently no diagnostic test for any neurodegenerative disease on the market -- diagnoses are currently based solely on a clinical diagnosis of symptoms," said chief executive, Steve Rash.
Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.
Although the test has been welcomed by Kieran Breen, director of research at the Parkinson's Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: "While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis."
Susan Sorensen, head of research at the UK Alzheimer's Society said: "There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer's disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.
"The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer's disease... Some suggest Alzheimer's, for example, is too complex to be identified in this way."
Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.
Note: (1) Expert Review of Proteomics 2008, 5(1), 1-8; Biochemical and Biophysical Research Communications 2006, 342, 1034-1039
Adapted from materials provided by Society of Chemical Industry, via EurekAlert!, a service of AAAS.
Statement by Cheryl Nickerson Hearing on NASA's International Space Station
[Source: House Science and Technology Committee ]
Cheryl A. Nickerson, Ph.D.
Associate Professor of Life Sciences, School of Life Sciences
Center for Infectious Diseases and Vaccinology
The Biodesign Institute
Arizona State University
Mr. Chairman, members of the Committee, thank you for inviting me to appear before you today to testify. My name is Cheryl Nickerson, and I am an Associate Professor in the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at Arizona State University. My research focuses on understanding the molecular mechanisms and processes of infectious disease, with an important emphasis on investigating the unique effect of spaceflight on microbial pathogen responses. NASA's support of my research has resulted in multiple spaceflight experiments, which have provided novel insight into how microbial pathogens cause infection both during flight and on Earth, and hold promise for new drug and vaccine development to combat infectious disease.
Through awards such as the Presidential Early Career Award for Scientists and Engineers, and independent research funding from grants totaling over three million dollars, NASA has consistently recognized my laboratory's contributions to the United States Space Program into infectious disease risks for the crew during spaceflight and the general public here on Earth. I also serve as a scientific consultant for NASA at the Johnson Space Center in support of their efforts to determine and mitigate microbial risks to the crew during flight, and was honored to be selected as a NASA Astronaut candidate finalist for the Astronaut class of 2004. That being said, the views expressed in today's testimony are my own, but I believe they reflect community concerns.
In your invitation letter asking me to testify before you today you asked a series of questions regarding the utilization prospects of ISS research that I would like to address now in sequence.
1. What has been the nature of your space-based research, and what have been your findings to date?
I would like to begin by applauding NASA's foresight in funding our spaceflight research in the field of infectious disease. We were initially funded by NASA's Office of Biological and Physical Research and are currently funded by both the Advanced Capabilities Division and the Human Research Program in the Explorations Systems Mission Directorate. The connection between spaceflight and its influence on infectious disease was not immediately clear 10 years ago when NASA initially funded our research. As a result, NASA's support of my research through multiple spaceflight experiments has allowed us to provide novel insight into the molecular mechanisms that microbial pathogens use to cause infectious disease both during flight and on Earth, and has exciting implications for translation into human health benefits, including the development of new drugs and vaccines for treatment and prevention.
While the eradication or control of many microbial diseases has dramatically improved the health outlook of our society, infectious diseases are still a leading cause of human death and illness worldwide. Infectious disease causes 35 percent of deaths worldwide, and is the world's biggest killer of children and young adults. Within the United States, infectious disease has a tremendous social, economic, and security impact. Total cost for infectious disease in the U.S. exceeds $120 billion annually due to direct medical and lost productivity costs. Moreover, the future is threatened by new and re-emerging infectious diseases, an alarming increase in antibiotic resistance, and the use of microbial agents as a bioterrorist threat. Thus, research platforms that offer new insight into how pathogens cause infection and disease are desperately needed and will lead to novel strategies for treatment and prevention.
To enhance our understanding of how pathogens cause disease in the infected host, my laboratory uses innovative approaches to investigate the molecular mechanisms of infectious disease. It was this search for novel approaches that drove our initial investigations with NASA technology. As flight experiments are a rare opportunity, our early experimental efforts concentrated on the use of a unique bioreactor, called the Rotating Wall Vessel (RWV), designed at the NASA Johnson Space Center in Houston as a ground-based spaceflight analogue. The RWV bioreactor allows scientists to culture cells (microbial or mammalian) in the laboratory under conditions that mimic several aspects of spaceflight and can be used to induce many of the biological changes that occur during spaceflight. In addition, by using mathematical modeling, we found that this analogue, and true spaceflight, produce an environment that is relevant to conditions encountered by the pathogen during infection in the human host - thus enhancing the relevance of our findings for the development of new strategies to combat infectious disease on Earth.
We chose the model bacterial pathogen Salmonella typhimurium for both our spaceflight analogue and spaceflight studies, as it is the best characterized pathogen and poses a risk to both the crew during flight and the general public on Earth. Salmonella is the most readily and fully understood pathogen and belongs to a large group of bacteria whose natural habitat is the intestinal tract of humans and animals. This group includes most of the bacteria that cause intestinal and diarrheal disease, considered to be one of the greatest health problems globally.
Indeed, Salmonella infection is one of the most common food-borne infections worldwide. In the United States an estimated 1.41 million
cases occur, resulting in 168,000 visits to physicians, 15,000 hospitalizations and 580 deaths annually. Salmonella accounts for approximately 30% of deaths caused by food- borne infections in the United States, and is even more detrimental in the developing world. The total cost associated with Salmonella infections in the US is estimated at three billion dollars annually. Moreover, in 1984, Salmonella was used in a bioterrorism attack by a religious cult in Oregon to cause a community-wide outbreak of foodborne illness in an attempt to influence the outcome of a local election. The organism is also an excellent choice for NASA as it is considered a potential threat to crew health as a food contaminant. There are currently no human vaccines to prevent Salmonella food borne illness.
Using the RWV ground-based technology, we conducted preliminary studies showing that Salmonella responded to this environment by globally altering its gene expression, stress resistance, and disease causing (virulence) profiles, thereby improving our chance of success and need for a spaceflight experiment. Subsequent analysis of the genes that were expressed after growth in this analogue suggested that the environment induced unique molecular mechanisms in the microbe to cause disease. Our information from these early experiments provided NASA with new insight toward understanding the risk of infection during flight. In addition, the unique molecular mechanisms that were identified held the potential to be used to develop new therapeutics and vaccines for the general public on Earth.
NASA and the scientific community continued their support of our ground-based findings by awarding us a grant to investigate the effect of true spaceflight on Salmonella virulence and gene expression responses. This was an exciting opportunity for us, as while the RWV bioreactor can simulate some aspects of the spaceflight environment, it cannot duplicate all of the physical parameters that organisms encounter during spaceflight or their biological responses. In September 2006, our first spaceflight experiment flew aboard STS-115, and we investigated the comprehensive changes in Salmonella when exposed to the truly unique environment of microgravity. The results from this experiment were remarkable and showed that during spaceflight, Salmonella altered its virulence and gene expression responses in unique ways that are not observed using traditional experimental approaches.
These findings immediately advanced our knowledge of microbial responses to spaceflight and disease causing mechanisms used by this important human pathogen. Our first technical report from this spaceflight experiment was recently published in the Proceedings of the National Academy of Sciences, and our results demonstrated changes in Salmonella disease causing potential (virulence) during flight as compared to identical samples that were grown on the ¬ground. Specifically, our findings demonstrated that spaceflight increased the virulence of Salmonella, and the pathogen was able to cause disease at lower doses. In addition, we identified 167 genes in Salmonella that changed expression in response to spaceflight. The identity of these genes allowed us to discover a key ¬"master switch" regulatory mechanism that controls Salmonella responses to spaceflight ¬environments. This molecular target, and others that we identified, hold potential to be translated into new therapeutic and vaccine approaches to treat and prevent human enteric salmonellosis.
This experiment was a "first of its kind" in spaceflight biological study. It was the first study ever to investigate the effect of spaceflight on the disease-causing potential (virulence) of a pathogen, and the first ever to obtain the entire gene expression response profiles of a bacterium to spaceflight. In fact, very few studies contain data that document gene expression changes during spaceflight. It is also critical to mention that an important part of our spaceflight work is directly related to helping us understand how microbial pathogens cause infectious disease here on Earth. This is possible because the the unique environment of spaceflight encountered by microorganisms (including pathogens) are also relevant to conditions that these cells encounter here on Earth during the normal course of their lifecycles, including certain niches within the infected host, such as parts of the human intestine. Thus, an exciting part of this work is the opportunity to use spaceflight and the ISS as a novel enabling research platform for innovations in infectious disease control here on Earth - including novel insight into how pathogens cause disease and for the development of new therapeutics and vaccines for treatment and prevention.
The success of our flight experiment aboard STS-115 inspired a follow-up experiment aboard STS-123, which just flew in March 2008. While the data is still being analyzed, our preliminary findings are leading toward translational applications of our original data for the development of novel strategies to treat and prevent infection and disease during flight and here on Earth. Shortly, we expect NASA and the public to receive a direct benefit from their investment.
The ISS holds tremendous potential to provide novel insight into human health and disease mechanisms that can lead to groundbreaking new treatments to combat infectious disease and improve the quality of life.
2. What is your perspective on the future potential for use of the microgravity environment as a research tool?
The microgravity of spaceflight offers a unique environment for ground-breaking biotechnology and biomedical innovations and discoveries to globally advance human health in the following areas:
- Infectious disease
- Immunology
- Cancer
- Aging
- Bone and muscle wasting diseases
- Development of biopharmaceuticals
- Tissue engineering
It is not surprising that biological systems respond in novel ways to the spaceflight environment. Many breakthroughs in life sciences research have come from studying living systems in unique and extreme environments. It is from studying the response of biological systems under these environments that we have not only gained new fundamental insight into how they function and adapt to extreme conditions, but have also translated these findings into beneficial biotechnology and biomedical advances to improve our quality of life. Spaceflight is simply the next logical progression and extreme environment to study that holds tremendous potential to provide the next ground- breaking advances in public health.
The ISS provides a unique environment where researchers can explore fundamental questions about human health - like how the body heals itself and develops disease. Specifically, the ISS offers an orbiting laboratory to use microgravity as a tool to bring a new technological approach to understanding living systems and discover basic mechanisms we haven't seen before. That is because organisms and cells respond in unique ways to spaceflight and exhibit characteristics relevant to human health and disease that they do not when cultured using traditional conditions on Earth. Accordingly, cellular and molecular mechanisms that underlie disease can be studied, offering new opportunities to see how cells operate in these conditions, and giving new fundamental insight into the disease process. Many of these findings may translate directly to the clinical setting for novel ways to diagnose, treat and prevent disease here on Earth. This type of research creates exciting new opportunities for the utilization of ISS to advance the frontiers of knowledge and act as a commercial platform for breakthrough biomedical and biotechnological discoveries. I believe it is important to take advantage of this unique research facility to develop new advances in biotech and biomedicine that will globally advance human health and benefit the United States in the international economy.
Thus, it is anticipated that ISS life sciences research will lead to ground-breaking discoveries and innovations in human health, biotech and biomedical innovations, and will have a lasting impact on our nation's scientific capability, economy, and quality of our lives.
3. What are any potential applications of the basic research you have conducted to date or intend to pursue?
The investment that NASA has made in our research for innovations in infectious disease treatment and control will provide long lasting return in the protection of humans as they explore space and for the general public here on Earth. Regarding protection of the crew, the negative impacts of infectious disease range from impeded crew performance to potentially life threatening scenarios. As humans travel further away from our home planet, the risk to crew health and mission success becomes even greater. As we gain greater knowledge of the risks of microbial infection, prudent preventative operational activities, therapeutics, and other countermeasures can be implemented to mitigate the risk to the crew and mission success.
Perhaps the greatest application from this research will not apply directly to spaceflight, but rather to improving the quality of life on Earth through the development of novel strategies to combat infection and disease. Internationally, we face many challenges to our health by microbial threats. Antibiotic resistant strains are on the rise, regional diseases are expanding to new locations, the threat of bioterrorism looms, and a multitude of diseases have insufficient treatments. New treatment paradigms and testing methods are desperately needed. The knowledge from spaceflight experiments is providing novel insight into how microbes cause disease in the human body and is providing new targets for therapeutic and vaccine development. The goal is to identify target mechanisms in space and then investigate these mechanisms on Earth. By understanding more fully how these organisms function and react to novel stimuli, we can develop new methods to treat and prevent the spread of infectious agents.
In addition, the knowledge gained from spaceflight research can advance and accelerate therapeutic development and implementation of new strategies for translation of this research into health benefits for the developing world. The costs of therapeutics and vaccine development can be prohibitively high. Bringing a new drug to market can cost in excess of one billion dollars over a decade before it reaches the patient. If the knowledge gained from spaceflight studies provides even an incremental decrease in these costs and timelines (which studies strongly suggest is the case), then this research is of tremendous importance.
An example of a potential boon from spaceflight experiments is our laboratory's discovery that gene regulatory proteins participate in the spaceflight mechanistic response of microbial pathogens. Gene regulatory proteins affect every property of a cell including its ability to cause disease. Our laboratory is currently focusing on how this regulatory pathway works in Salmonella and how it can be manipulated to control that organism's virulence in flight and here on Earth. Once understood, we will use that knowledge to see which other microorganisms can be controlled in a similar fashion. A detailed understanding of how these gene regulatory proteins are controlled may offer new opportunities to design efficacious drugs and vaccines that would target this class of protein.
It is also relevant to note that there are exciting efforts underway to develop a nationwide Biotechnology Space Research Alliance (BSRA) Consortium that partners a world-class team of industry, university, and economic development organizations across the country to partner with NASA to utilize the ISS for breakthrough biomedical and biotechnology discoveries. It is anticipated that the discoveries made on ISS will engender scientific knowledge, technological capability, and commerce on Earth as a gateway to 21st Century exploration and development of space.
One key to our nation's economic success has been its ability to provide unique answers to the world's problems. We have the opportunity to advance in a field where the United States is a world leader. I believe space exploration and development will be one of the defining activities for our nation that will lead the world in this new millennium.
Cheryl A. Nickerson, Ph.D.
Associate Professor of Life Sciences, School of Life Sciences
Center for Infectious Diseases and Vaccinology
The Biodesign Institute
Arizona State University
Mr. Chairman, members of the Committee, thank you for inviting me to appear before you today to testify. My name is Cheryl Nickerson, and I am an Associate Professor in the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at Arizona State University. My research focuses on understanding the molecular mechanisms and processes of infectious disease, with an important emphasis on investigating the unique effect of spaceflight on microbial pathogen responses. NASA's support of my research has resulted in multiple spaceflight experiments, which have provided novel insight into how microbial pathogens cause infection both during flight and on Earth, and hold promise for new drug and vaccine development to combat infectious disease.
Through awards such as the Presidential Early Career Award for Scientists and Engineers, and independent research funding from grants totaling over three million dollars, NASA has consistently recognized my laboratory's contributions to the United States Space Program into infectious disease risks for the crew during spaceflight and the general public here on Earth. I also serve as a scientific consultant for NASA at the Johnson Space Center in support of their efforts to determine and mitigate microbial risks to the crew during flight, and was honored to be selected as a NASA Astronaut candidate finalist for the Astronaut class of 2004. That being said, the views expressed in today's testimony are my own, but I believe they reflect community concerns.
In your invitation letter asking me to testify before you today you asked a series of questions regarding the utilization prospects of ISS research that I would like to address now in sequence.
1. What has been the nature of your space-based research, and what have been your findings to date?
I would like to begin by applauding NASA's foresight in funding our spaceflight research in the field of infectious disease. We were initially funded by NASA's Office of Biological and Physical Research and are currently funded by both the Advanced Capabilities Division and the Human Research Program in the Explorations Systems Mission Directorate. The connection between spaceflight and its influence on infectious disease was not immediately clear 10 years ago when NASA initially funded our research. As a result, NASA's support of my research through multiple spaceflight experiments has allowed us to provide novel insight into the molecular mechanisms that microbial pathogens use to cause infectious disease both during flight and on Earth, and has exciting implications for translation into human health benefits, including the development of new drugs and vaccines for treatment and prevention.
While the eradication or control of many microbial diseases has dramatically improved the health outlook of our society, infectious diseases are still a leading cause of human death and illness worldwide. Infectious disease causes 35 percent of deaths worldwide, and is the world's biggest killer of children and young adults. Within the United States, infectious disease has a tremendous social, economic, and security impact. Total cost for infectious disease in the U.S. exceeds $120 billion annually due to direct medical and lost productivity costs. Moreover, the future is threatened by new and re-emerging infectious diseases, an alarming increase in antibiotic resistance, and the use of microbial agents as a bioterrorist threat. Thus, research platforms that offer new insight into how pathogens cause infection and disease are desperately needed and will lead to novel strategies for treatment and prevention.
To enhance our understanding of how pathogens cause disease in the infected host, my laboratory uses innovative approaches to investigate the molecular mechanisms of infectious disease. It was this search for novel approaches that drove our initial investigations with NASA technology. As flight experiments are a rare opportunity, our early experimental efforts concentrated on the use of a unique bioreactor, called the Rotating Wall Vessel (RWV), designed at the NASA Johnson Space Center in Houston as a ground-based spaceflight analogue. The RWV bioreactor allows scientists to culture cells (microbial or mammalian) in the laboratory under conditions that mimic several aspects of spaceflight and can be used to induce many of the biological changes that occur during spaceflight. In addition, by using mathematical modeling, we found that this analogue, and true spaceflight, produce an environment that is relevant to conditions encountered by the pathogen during infection in the human host - thus enhancing the relevance of our findings for the development of new strategies to combat infectious disease on Earth.
We chose the model bacterial pathogen Salmonella typhimurium for both our spaceflight analogue and spaceflight studies, as it is the best characterized pathogen and poses a risk to both the crew during flight and the general public on Earth. Salmonella is the most readily and fully understood pathogen and belongs to a large group of bacteria whose natural habitat is the intestinal tract of humans and animals. This group includes most of the bacteria that cause intestinal and diarrheal disease, considered to be one of the greatest health problems globally.
Indeed, Salmonella infection is one of the most common food-borne infections worldwide. In the United States an estimated 1.41 million
cases occur, resulting in 168,000 visits to physicians, 15,000 hospitalizations and 580 deaths annually. Salmonella accounts for approximately 30% of deaths caused by food- borne infections in the United States, and is even more detrimental in the developing world. The total cost associated with Salmonella infections in the US is estimated at three billion dollars annually. Moreover, in 1984, Salmonella was used in a bioterrorism attack by a religious cult in Oregon to cause a community-wide outbreak of foodborne illness in an attempt to influence the outcome of a local election. The organism is also an excellent choice for NASA as it is considered a potential threat to crew health as a food contaminant. There are currently no human vaccines to prevent Salmonella food borne illness.
Using the RWV ground-based technology, we conducted preliminary studies showing that Salmonella responded to this environment by globally altering its gene expression, stress resistance, and disease causing (virulence) profiles, thereby improving our chance of success and need for a spaceflight experiment. Subsequent analysis of the genes that were expressed after growth in this analogue suggested that the environment induced unique molecular mechanisms in the microbe to cause disease. Our information from these early experiments provided NASA with new insight toward understanding the risk of infection during flight. In addition, the unique molecular mechanisms that were identified held the potential to be used to develop new therapeutics and vaccines for the general public on Earth.
NASA and the scientific community continued their support of our ground-based findings by awarding us a grant to investigate the effect of true spaceflight on Salmonella virulence and gene expression responses. This was an exciting opportunity for us, as while the RWV bioreactor can simulate some aspects of the spaceflight environment, it cannot duplicate all of the physical parameters that organisms encounter during spaceflight or their biological responses. In September 2006, our first spaceflight experiment flew aboard STS-115, and we investigated the comprehensive changes in Salmonella when exposed to the truly unique environment of microgravity. The results from this experiment were remarkable and showed that during spaceflight, Salmonella altered its virulence and gene expression responses in unique ways that are not observed using traditional experimental approaches.
These findings immediately advanced our knowledge of microbial responses to spaceflight and disease causing mechanisms used by this important human pathogen. Our first technical report from this spaceflight experiment was recently published in the Proceedings of the National Academy of Sciences, and our results demonstrated changes in Salmonella disease causing potential (virulence) during flight as compared to identical samples that were grown on the ¬ground. Specifically, our findings demonstrated that spaceflight increased the virulence of Salmonella, and the pathogen was able to cause disease at lower doses. In addition, we identified 167 genes in Salmonella that changed expression in response to spaceflight. The identity of these genes allowed us to discover a key ¬"master switch" regulatory mechanism that controls Salmonella responses to spaceflight ¬environments. This molecular target, and others that we identified, hold potential to be translated into new therapeutic and vaccine approaches to treat and prevent human enteric salmonellosis.
This experiment was a "first of its kind" in spaceflight biological study. It was the first study ever to investigate the effect of spaceflight on the disease-causing potential (virulence) of a pathogen, and the first ever to obtain the entire gene expression response profiles of a bacterium to spaceflight. In fact, very few studies contain data that document gene expression changes during spaceflight. It is also critical to mention that an important part of our spaceflight work is directly related to helping us understand how microbial pathogens cause infectious disease here on Earth. This is possible because the the unique environment of spaceflight encountered by microorganisms (including pathogens) are also relevant to conditions that these cells encounter here on Earth during the normal course of their lifecycles, including certain niches within the infected host, such as parts of the human intestine. Thus, an exciting part of this work is the opportunity to use spaceflight and the ISS as a novel enabling research platform for innovations in infectious disease control here on Earth - including novel insight into how pathogens cause disease and for the development of new therapeutics and vaccines for treatment and prevention.
The success of our flight experiment aboard STS-115 inspired a follow-up experiment aboard STS-123, which just flew in March 2008. While the data is still being analyzed, our preliminary findings are leading toward translational applications of our original data for the development of novel strategies to treat and prevent infection and disease during flight and here on Earth. Shortly, we expect NASA and the public to receive a direct benefit from their investment.
The ISS holds tremendous potential to provide novel insight into human health and disease mechanisms that can lead to groundbreaking new treatments to combat infectious disease and improve the quality of life.
2. What is your perspective on the future potential for use of the microgravity environment as a research tool?
The microgravity of spaceflight offers a unique environment for ground-breaking biotechnology and biomedical innovations and discoveries to globally advance human health in the following areas:
- Infectious disease
- Immunology
- Cancer
- Aging
- Bone and muscle wasting diseases
- Development of biopharmaceuticals
- Tissue engineering
It is not surprising that biological systems respond in novel ways to the spaceflight environment. Many breakthroughs in life sciences research have come from studying living systems in unique and extreme environments. It is from studying the response of biological systems under these environments that we have not only gained new fundamental insight into how they function and adapt to extreme conditions, but have also translated these findings into beneficial biotechnology and biomedical advances to improve our quality of life. Spaceflight is simply the next logical progression and extreme environment to study that holds tremendous potential to provide the next ground- breaking advances in public health.
The ISS provides a unique environment where researchers can explore fundamental questions about human health - like how the body heals itself and develops disease. Specifically, the ISS offers an orbiting laboratory to use microgravity as a tool to bring a new technological approach to understanding living systems and discover basic mechanisms we haven't seen before. That is because organisms and cells respond in unique ways to spaceflight and exhibit characteristics relevant to human health and disease that they do not when cultured using traditional conditions on Earth. Accordingly, cellular and molecular mechanisms that underlie disease can be studied, offering new opportunities to see how cells operate in these conditions, and giving new fundamental insight into the disease process. Many of these findings may translate directly to the clinical setting for novel ways to diagnose, treat and prevent disease here on Earth. This type of research creates exciting new opportunities for the utilization of ISS to advance the frontiers of knowledge and act as a commercial platform for breakthrough biomedical and biotechnological discoveries. I believe it is important to take advantage of this unique research facility to develop new advances in biotech and biomedicine that will globally advance human health and benefit the United States in the international economy.
Thus, it is anticipated that ISS life sciences research will lead to ground-breaking discoveries and innovations in human health, biotech and biomedical innovations, and will have a lasting impact on our nation's scientific capability, economy, and quality of our lives.
3. What are any potential applications of the basic research you have conducted to date or intend to pursue?
The investment that NASA has made in our research for innovations in infectious disease treatment and control will provide long lasting return in the protection of humans as they explore space and for the general public here on Earth. Regarding protection of the crew, the negative impacts of infectious disease range from impeded crew performance to potentially life threatening scenarios. As humans travel further away from our home planet, the risk to crew health and mission success becomes even greater. As we gain greater knowledge of the risks of microbial infection, prudent preventative operational activities, therapeutics, and other countermeasures can be implemented to mitigate the risk to the crew and mission success.
Perhaps the greatest application from this research will not apply directly to spaceflight, but rather to improving the quality of life on Earth through the development of novel strategies to combat infection and disease. Internationally, we face many challenges to our health by microbial threats. Antibiotic resistant strains are on the rise, regional diseases are expanding to new locations, the threat of bioterrorism looms, and a multitude of diseases have insufficient treatments. New treatment paradigms and testing methods are desperately needed. The knowledge from spaceflight experiments is providing novel insight into how microbes cause disease in the human body and is providing new targets for therapeutic and vaccine development. The goal is to identify target mechanisms in space and then investigate these mechanisms on Earth. By understanding more fully how these organisms function and react to novel stimuli, we can develop new methods to treat and prevent the spread of infectious agents.
In addition, the knowledge gained from spaceflight research can advance and accelerate therapeutic development and implementation of new strategies for translation of this research into health benefits for the developing world. The costs of therapeutics and vaccine development can be prohibitively high. Bringing a new drug to market can cost in excess of one billion dollars over a decade before it reaches the patient. If the knowledge gained from spaceflight studies provides even an incremental decrease in these costs and timelines (which studies strongly suggest is the case), then this research is of tremendous importance.
An example of a potential boon from spaceflight experiments is our laboratory's discovery that gene regulatory proteins participate in the spaceflight mechanistic response of microbial pathogens. Gene regulatory proteins affect every property of a cell including its ability to cause disease. Our laboratory is currently focusing on how this regulatory pathway works in Salmonella and how it can be manipulated to control that organism's virulence in flight and here on Earth. Once understood, we will use that knowledge to see which other microorganisms can be controlled in a similar fashion. A detailed understanding of how these gene regulatory proteins are controlled may offer new opportunities to design efficacious drugs and vaccines that would target this class of protein.
It is also relevant to note that there are exciting efforts underway to develop a nationwide Biotechnology Space Research Alliance (BSRA) Consortium that partners a world-class team of industry, university, and economic development organizations across the country to partner with NASA to utilize the ISS for breakthrough biomedical and biotechnology discoveries. It is anticipated that the discoveries made on ISS will engender scientific knowledge, technological capability, and commerce on Earth as a gateway to 21st Century exploration and development of space.
One key to our nation's economic success has been its ability to provide unique answers to the world's problems. We have the opportunity to advance in a field where the United States is a world leader. I believe space exploration and development will be one of the defining activities for our nation that will lead the world in this new millennium.
Quest for new antibiotics leads to novel sources
[Source: Susan J. Landers, AMNews] - Washington -- As bacteria become resistant to increasing numbers of antibiotics the search is on for new and effective antimicrobials. Researchers are hunting near and far -- on the ground and even in the swamps.
For instance, the minerals from certain clays, which have been used medicinally for thousands of years, could form the basis of a new generation of inexpensive antibiotics, researchers from Arizona State University reported at the national meeting of the American Chemical Society in New Orleans, April 6-10.
And proteins found in alligator blood are being eyed as powerful new medications that could help fight infections associated with diabetic ulcers, severe burns and the "superbugs" that are raising fears in the medical community. The alligator study was also presented at the chemical society's meeting.
The list of diseases that are becoming more difficult to fight with first-line antibiotics is growing longer. Included are tuberculosis, staph and strep infections, malaria, head lice and, recently, meningococcal disease. Methicillin-resistant Staphylococcus aureus, or MRSA, is particularly notorious for making the jump from a hospital problem to one that causes illness and deaths in communities.
This dangerous trend has prompted efforts by public health and medical societies, including the AMA, to educate physicians about the importance of appropriately prescribing antibiotics and the need to inform patients about the dangers of antimicrobial resistance.
Thinking outside the box
The importance of the quest for new medications has sparked interest in the healing powers of clay. "The catch word is MRSA," said Shelley Haydel, PhD, assistant professor in the School of Life Sciences and the Biodesign Institute at Arizona State University in Tempe. "We've shown in the laboratory that [some clay] does have some effectiveness at killing MRSA."
Clay's power was a surprise to Dr. Haydel. "When I first got involved, I looked at it with a skeptical eye," she said. But when a paste of clay killed bacteria in 12 hours, she was hooked. Dr. Haydel and her colleagues have screened about 30 different clays -- samples from all over the world -- and found three with antimicrobial properties.
Some clay has antimicrobial properties.
Dr. Haydel isn't sure what the medical community's response will be to this unorthodox approach. "We have to show that it is safe -- and we believe that it is safe because it's been used for so long -- and effective at getting rid of infections in test subjects.
"If we don't have to know exactly how it is working and just show that it is working and not causing additional harm, we may be a couple of years away from clinical use."
Meanwhile, Mark Merchant, PhD, assistant professor of biochemistry at McNeese State University in Lake Charles, La., is wrestling alligators in the pursuit for a new antibiotic. After subduing a gator he extracts blood.
Previous studies by Dr. Merchant showed that alligators have unusually strong immune systems that can fight fungi, viruses and bacteria without having prior exposure to them. Scientists believe this is an evolutionary adaptation to promote quick wound healing, as alligators are often injured during territorial battles in the unhygienic world they inhabit.
Dr. Merchant and colleagues have already isolated white blood cells and extracted the active proteins.
"We're very excited about the potential of these alligator blood proteins as both antibacterial and antifungal agents," he said. "There is a real possibility that you could be treated with an alligator blood product one day." However, that day is not likely to arrive for seven to 10 years.
In another development, the Food and Drug Administration approved a test April 3 that allows rapid screening for MRSA. The nasal test, which will provide results within 24 hours according to the manufacturer, improves on the two-day wait that had been necessary previously.
For instance, the minerals from certain clays, which have been used medicinally for thousands of years, could form the basis of a new generation of inexpensive antibiotics, researchers from Arizona State University reported at the national meeting of the American Chemical Society in New Orleans, April 6-10.
And proteins found in alligator blood are being eyed as powerful new medications that could help fight infections associated with diabetic ulcers, severe burns and the "superbugs" that are raising fears in the medical community. The alligator study was also presented at the chemical society's meeting.
The list of diseases that are becoming more difficult to fight with first-line antibiotics is growing longer. Included are tuberculosis, staph and strep infections, malaria, head lice and, recently, meningococcal disease. Methicillin-resistant Staphylococcus aureus, or MRSA, is particularly notorious for making the jump from a hospital problem to one that causes illness and deaths in communities.
This dangerous trend has prompted efforts by public health and medical societies, including the AMA, to educate physicians about the importance of appropriately prescribing antibiotics and the need to inform patients about the dangers of antimicrobial resistance.
Thinking outside the box
The importance of the quest for new medications has sparked interest in the healing powers of clay. "The catch word is MRSA," said Shelley Haydel, PhD, assistant professor in the School of Life Sciences and the Biodesign Institute at Arizona State University in Tempe. "We've shown in the laboratory that [some clay] does have some effectiveness at killing MRSA."
Clay's power was a surprise to Dr. Haydel. "When I first got involved, I looked at it with a skeptical eye," she said. But when a paste of clay killed bacteria in 12 hours, she was hooked. Dr. Haydel and her colleagues have screened about 30 different clays -- samples from all over the world -- and found three with antimicrobial properties.
Some clay has antimicrobial properties.
Dr. Haydel isn't sure what the medical community's response will be to this unorthodox approach. "We have to show that it is safe -- and we believe that it is safe because it's been used for so long -- and effective at getting rid of infections in test subjects.
"If we don't have to know exactly how it is working and just show that it is working and not causing additional harm, we may be a couple of years away from clinical use."
Meanwhile, Mark Merchant, PhD, assistant professor of biochemistry at McNeese State University in Lake Charles, La., is wrestling alligators in the pursuit for a new antibiotic. After subduing a gator he extracts blood.
Previous studies by Dr. Merchant showed that alligators have unusually strong immune systems that can fight fungi, viruses and bacteria without having prior exposure to them. Scientists believe this is an evolutionary adaptation to promote quick wound healing, as alligators are often injured during territorial battles in the unhygienic world they inhabit.
Dr. Merchant and colleagues have already isolated white blood cells and extracted the active proteins.
"We're very excited about the potential of these alligator blood proteins as both antibacterial and antifungal agents," he said. "There is a real possibility that you could be treated with an alligator blood product one day." However, that day is not likely to arrive for seven to 10 years.
In another development, the Food and Drug Administration approved a test April 3 that allows rapid screening for MRSA. The nasal test, which will provide results within 24 hours according to the manufacturer, improves on the two-day wait that had been necessary previously.
Scientists make chemical cousin of DNA for use as new nanotechnology building block
[Source: Joe Caspermeyer, Arizona State University]- In the rapid and fast-growing world of nanotechnology, researchers are continually on the lookout for new building blocks to push innovation and discovery to scales much smaller than the tiniest speck of dust.
In the Biodesign Institute at Arizona State University, researchers are using DNA to make intricate nano-sized objects. Working at this scale holds great potential for advancing medical and electronic applications. DNA, often thought of as the molecule of life, is an ideal building block for nanotechnology because they self-assemble, snapping together into shapes based on natural chemical rules of attraction. This is a major advantage for Biodesign researchers like Hao Yan, who rely on the unique chemical and physical properties of DNA to make their complex nanostructures.
While scientists are fully exploring the promise of DNA nanotechnology, Biodesign Institute colleague John Chaput is working to give researchers brand new materials to aid their designs. In an article recently published in the Journal of the American Chemical Society, Chaput and his research team have made the first self-assembled nanostructures composed entirely of glycerol nucleic acid (GNA)—a synthetic analog of DNA.
“Everyone in DNA nanotechnology is essentially limited by what they can buy off the shelf,” said Chaput, who is also an ASU assistant professor in the Department of Chemistry and Biochemistry. “We wanted to build synthetic molecules that assembled like DNA, but had additional properties not found in natural DNA.”
The DNA helix is made up of just three simple parts: a sugar and a phosphate molecule that form the backbone of the DNA ladder, and one of four nitrogenous bases that make up the rungs. The nitrogenous base pairing rules in the DNA chemical alphabet fold DNA into a variety of useful shapes for nanotechnology, given that "A" can only form a zipper-like chemical bond with "T" and "G" only pair with "C."
In the case of GNA, the sugar is the only difference with DNA. The five carbon sugar commonly found in DNA, called deoxyribose, is substituted by glycerol, which contains just three carbon atoms.
Chaput has had a long-standing interest in tinkering with chemical building blocks used to make molecules like proteins and nucleic acids that do not exist in nature. When it came time to synthesize the first self-assembled GNA nanostructures, Chaput had to go back to basics. “The idea behind the research was what to start with a simple DNA nanostructure that we could just mimic.”
The first self-assembled DNA nanostructure was made by Ned Seeman’s lab at Columbia University in 1998, the very same laboratory where ASU professor Hao Yan received his Ph.D. Chaput’s team, which includes graduate students Richard Zhang and Elizabeth McCullum were not only able to duplicate these structures, but, unique to GNA, found they could make mirror image nanostructures.
In nature, many molecules important to life like DNA and proteins have evolved to exist only as right-handed. The GNA structures, unlike DNA, turned out to be ‘enantiomeric’ molecules, which in chemical terms means both left and right-handed.
“Making GNA is not tricky, it’s just three steps, and with three carbon atoms, only one stereo center,” said Chaput. “It allows us to make these right and left-handed biomolecules. People have actually made left-handed DNA, but it is a synthetic nightmare. To use it for DNA nanotechnology could never work. It’s too high of a cost to make, so one could never get enough material.”
The ability to make mirror image structures opens up new possibilities for making nanostructures. The research team also found a number of physical and chemical properties that were unique to GNA, including having a higher tolerance to heat than DNA nanostructures. Now, with a new material in hand, which Chaput dubs ‘unnatural nucleic acid nanostructures,’ the group hopes to explore the limits on the topology and types of structure they can make.
“We think we can take this as a basic building block and begin to build more elaborate structures in 2-D and see them in atomic force microscopy images,” said Chaput. “I think it will be interesting to see where it will all go. Researchers come up with all of these clever designs now.”
Women attack heart disease
[Source: Susie Steckner, Special for The Republic] - Admit it, you could probably eat more healthful food, exercise more and take better care of yourself. Add your high-stress job into the mix, and you've increased your risk of heart disease.
As a health-care executive and mother of three, Ruby Majhail was a heart attack waiting to happen.
Genetics, a stressful job, and poor diet and exercise habits conspired against Majhail, bringing a life-threatening diagnosis and a critical vow to make changes.
Today, Majhail has dramatically reduced her heart-attack risk by exercising and watching her diet.
"As you get older, it's like, 'Wait a minute, I need to change my lifestyle. Otherwise, this will come back to haunt me,' " said Majhail, 40, market chief financial officer overseeing Arizona and Nevada for IASIS Healthcare.
Sadly, too many women are missing the message.
Heart disease continues to be the No. 1 killer of women in the United States. In 2006, more than 4,800 Arizona women died of it. In the past decade, more than 53,100 women in the state have lost their lives to it, according to the Arizona Department of Health Services.
Though women older than 65 are most affected, women in their 40s, 50s and early 60s are still at substantial risk. For many, high-stress and deadline-heavy jobs add to that threat, medical studies show.
Women in high-powered jobs are at nearly three times the risk of developing heart disease than working women with less authority and demands, according to a 2002 Framingham Offspring Study.
Another study in 2004 found that women and men in the workplace are six times more likely to have a heart attack 24 hours after a major deadline. Other risk factors for women include taking on unwanted responsibilities at work over the course of a year, researchers at the Karolinska Institute in Sweden found.
If there's good news, experts say, it's that women are becoming increasingly aware of their heart-disease risks through efforts such as the American Heart Association's Go Red for Women educational campaign. A 2006 survey by the association showed that 57 percent of women polled know heart disease is the leading killer of women, up from 34 percent in 2000.
Arizona key in research
In coming years, Arizona could play a key role in the fight against heart disease.
The Translational Genomics Research Institute in Phoenix is developing plans for two initiatives, said Johanna Wolford, 43, director of TGen's diabetics, cardiovascular and metabolic disease division.
The organization wants to partner with Arizona State University and Scottsdale Healthcare to create outcomes-research centers in order to monitor which treatments are helping prevent heart disease.
It also wants to team up with the University of Arizona to create a center for cardiovascular pharmacogenomics, which would identify the best therapeutic interventions for people at risk for heart disease.
TGen also is in preliminary talks with ASU about developing a cardiovascular outcomes-research center that focuses on ethnically diverse populations.
As TGen looks to the future, there are prevention strategies women can implement today.
Preventing the disease
Diet and exercise are critical. Women should maintain a well-balanced diet and work toward 30 minutes of activity every day, said Adriana Perez, 32, a cardiovascular nurse at St. Joseph's Hospital and Medical Center and a Go Red volunteer.
Managing stress also is important. Perez suggests developing a social support system, with a mix of family, friends and neighbors, to help cope with stress.
Women should watch for conditions such as diabetes and high blood pressure that can lead to severe heart disease, and they should quit smoking.
Majhail realized she needed to make changes five years ago, when tests showed that the level of her triglycerides - a type of fat - was in the 700s; a healthy level is about 150. She also was at risk because she's Asian-Indian, a group that has a high rate of heart disease.
She began a new diet and exercise regimen. Her triglyceride level is now at about 250.
As a health-care executive and mother of three, Ruby Majhail was a heart attack waiting to happen.
Genetics, a stressful job, and poor diet and exercise habits conspired against Majhail, bringing a life-threatening diagnosis and a critical vow to make changes.
Today, Majhail has dramatically reduced her heart-attack risk by exercising and watching her diet.
"As you get older, it's like, 'Wait a minute, I need to change my lifestyle. Otherwise, this will come back to haunt me,' " said Majhail, 40, market chief financial officer overseeing Arizona and Nevada for IASIS Healthcare.
Sadly, too many women are missing the message.
Heart disease continues to be the No. 1 killer of women in the United States. In 2006, more than 4,800 Arizona women died of it. In the past decade, more than 53,100 women in the state have lost their lives to it, according to the Arizona Department of Health Services.
Though women older than 65 are most affected, women in their 40s, 50s and early 60s are still at substantial risk. For many, high-stress and deadline-heavy jobs add to that threat, medical studies show.
Women in high-powered jobs are at nearly three times the risk of developing heart disease than working women with less authority and demands, according to a 2002 Framingham Offspring Study.
Another study in 2004 found that women and men in the workplace are six times more likely to have a heart attack 24 hours after a major deadline. Other risk factors for women include taking on unwanted responsibilities at work over the course of a year, researchers at the Karolinska Institute in Sweden found.
If there's good news, experts say, it's that women are becoming increasingly aware of their heart-disease risks through efforts such as the American Heart Association's Go Red for Women educational campaign. A 2006 survey by the association showed that 57 percent of women polled know heart disease is the leading killer of women, up from 34 percent in 2000.
Arizona key in research
In coming years, Arizona could play a key role in the fight against heart disease.
The Translational Genomics Research Institute in Phoenix is developing plans for two initiatives, said Johanna Wolford, 43, director of TGen's diabetics, cardiovascular and metabolic disease division.
The organization wants to partner with Arizona State University and Scottsdale Healthcare to create outcomes-research centers in order to monitor which treatments are helping prevent heart disease.
It also wants to team up with the University of Arizona to create a center for cardiovascular pharmacogenomics, which would identify the best therapeutic interventions for people at risk for heart disease.
TGen also is in preliminary talks with ASU about developing a cardiovascular outcomes-research center that focuses on ethnically diverse populations.
As TGen looks to the future, there are prevention strategies women can implement today.
Preventing the disease
Diet and exercise are critical. Women should maintain a well-balanced diet and work toward 30 minutes of activity every day, said Adriana Perez, 32, a cardiovascular nurse at St. Joseph's Hospital and Medical Center and a Go Red volunteer.
Managing stress also is important. Perez suggests developing a social support system, with a mix of family, friends and neighbors, to help cope with stress.
Women should watch for conditions such as diabetes and high blood pressure that can lead to severe heart disease, and they should quit smoking.
Majhail realized she needed to make changes five years ago, when tests showed that the level of her triglycerides - a type of fat - was in the 700s; a healthy level is about 150. She also was at risk because she's Asian-Indian, a group that has a high rate of heart disease.
She began a new diet and exercise regimen. Her triglyceride level is now at about 250.
MMRC Genomics Initiative Presents Two Abstracts at American Association of Cancer Research (AACR) 2008 Annual Meeting
[Source: PharmaLive.com] - The Multiple Myeloma Research Consortium (MMRC), presented two abstracts during the 2008 Annual Meeting of the American Association of Cancer Research, including one that was selected for oral presentation, based on data from the MMRC Multiple Myeloma Genomics Initiative.
In an oral session, Daniel Auclair, PhD, manager of the Initiative for the MMRC, presented "Clues from the MMRC Genomics Initiative about the Multiple Myeloma Druggable Genome". The clues emerge from a preliminary analysis of an initial set of 100 patient tissue samples using high-resolution array-based comparative genomic hybridization (aCGH) and gene expression profiling (GEP) technologies. An analysis of these tissue samples, collected through the MMRC Tissue Bank, highlight novel genetic abnormalities and identify potential new druggable targets and pathways in multiple myeloma. This updated dataset is freely available to the scientific community through the Multiple Myeloma Genomics Portal, the world's only myeloma-specific repository of genomic data.
In addition, details were provided about the multiple myeloma genome re-sequencing project planned to be performed in collaboration with the Eli and Edythe L. Broad Institute of MIT and Harvard on 250 patient tumor samples and matched peripheral blood. The sequencing of all the genes expressed in myeloma tumor cells (~10,000 genes) will be done on state-of-the-art next generation single molecule sequencing instruments. These instruments represent the newest, most accurate and cost effective technology available today for genome re-sequencing.
"The expanded sequencing project is perfect in its timing. The project has the potential to yield specific findings for myeloma and help set the standard for cancer genome sequencing in other diseases," said Todd R. Golub, MD, Director of the Cancer Program at the Eli and Edythe L. Broad Institute of MIT and Harvard, physician at Dana Farber Cancer Institute, and co-Principal Investigator of the MMRC Genomics Initiative. ?Coupled with the breadth of the data from the entire Initiative, these sequencing results will play a pivotal role in identifying new targets and approaches for treating patients with myeloma."
In a second presentation, "Validation of NF-kB pathway mutations in myeloma using data from the MMRC Genomics Initiative", Angela Baker, PhD, Translational Genomics Research Institute, disclosed that by using data from the Initiative and by correlating changes in gene expression and DNA copy number, her group identified several genes involved in the NF-kB pathway in myeloma. The results of this study aid in the validation of previous findings on this pathway and may ultimately lead to new targets for the treatment of multiple myeloma.
"The Multiple Myeloma Genomics Initiative is critical in generating data that will help MMRC researchers make significant progress in identifying new therapeutic targets for more effective therapies," states MMRF and MMRC Founder and CEO, Kathy Giusti, who is also a myeloma patient.
In an oral session, Daniel Auclair, PhD, manager of the Initiative for the MMRC, presented "Clues from the MMRC Genomics Initiative about the Multiple Myeloma Druggable Genome". The clues emerge from a preliminary analysis of an initial set of 100 patient tissue samples using high-resolution array-based comparative genomic hybridization (aCGH) and gene expression profiling (GEP) technologies. An analysis of these tissue samples, collected through the MMRC Tissue Bank, highlight novel genetic abnormalities and identify potential new druggable targets and pathways in multiple myeloma. This updated dataset is freely available to the scientific community through the Multiple Myeloma Genomics Portal, the world's only myeloma-specific repository of genomic data.
In addition, details were provided about the multiple myeloma genome re-sequencing project planned to be performed in collaboration with the Eli and Edythe L. Broad Institute of MIT and Harvard on 250 patient tumor samples and matched peripheral blood. The sequencing of all the genes expressed in myeloma tumor cells (~10,000 genes) will be done on state-of-the-art next generation single molecule sequencing instruments. These instruments represent the newest, most accurate and cost effective technology available today for genome re-sequencing.
"The expanded sequencing project is perfect in its timing. The project has the potential to yield specific findings for myeloma and help set the standard for cancer genome sequencing in other diseases," said Todd R. Golub, MD, Director of the Cancer Program at the Eli and Edythe L. Broad Institute of MIT and Harvard, physician at Dana Farber Cancer Institute, and co-Principal Investigator of the MMRC Genomics Initiative. ?Coupled with the breadth of the data from the entire Initiative, these sequencing results will play a pivotal role in identifying new targets and approaches for treating patients with myeloma."
In a second presentation, "Validation of NF-kB pathway mutations in myeloma using data from the MMRC Genomics Initiative", Angela Baker, PhD, Translational Genomics Research Institute, disclosed that by using data from the Initiative and by correlating changes in gene expression and DNA copy number, her group identified several genes involved in the NF-kB pathway in myeloma. The results of this study aid in the validation of previous findings on this pathway and may ultimately lead to new targets for the treatment of multiple myeloma.
"The Multiple Myeloma Genomics Initiative is critical in generating data that will help MMRC researchers make significant progress in identifying new therapeutic targets for more effective therapies," states MMRF and MMRC Founder and CEO, Kathy Giusti, who is also a myeloma patient.
Monday, April 28, 2008
Rats facing NAU spay chemical
[Source:CYNDY COLE, Arizona Daily Sun Staff Reporter] - As the United Nations warns of a global crisis and residents of more than a dozen countries riot because of rapidly increasing food prices, rice-field rats in Southeast Asia are chowing down in the world's rice bowl.
The rodents, able to produce 600 offspring from one pair in a few months, have sometimes eaten one-third of the rice crops and are raising a famine scare in India. General anti-coagulant poisons knock back the populations, but they always rebound.
"With the food shortages that are starting to erupt, this is huge," said Cheryl Dyer, researcher and ovarian physiologist at Northern Arizona University.
She and NAU scientists Loretta Mayer and Timothy Vail have helped create a product that could knock back the rat population, and nonsurgically sterilize female dogs, cats and other vertebrate pest species.
The idea might someday replace surgeries to spay domestic pets, help control packs of rabid dogs in Africa -- or find popularity in Spain, where pied pipers tried last year to drive crop-eating rodents from their fields with the use of flutes.
And if rice-growing countries were to spay rats and save 10 percent more of their crops per year, it would be enough to feed 380 million people.
The product came from the discovery that an industrial compound found in the plastics industry could accelerate the aging process in rodents, but affect no other part of the body.
"I saw it and said, 'That's my model for menopause,'" Mayer said.
Pharmaceutical companies had been testing drugs for human on mice and rats with their female reproductive organs removed.
This compound kept the organs intact, to cause chemical sterilization, more closely simulating menopause in women.
In short, it created a better lab mouse.
And the compound is short-lived, posing less environmental and food-chain risk than the anticoagulants now used to poison rice-field rats and whatever other animals consume the bait.
Rice-producing countries are currently spending more than $1 billion annually on poison, Mayer said, while chemists must continually rework the poisons to keep ahead of animal resistance.
This chemical compound, named ContraPest, is to be used in the rice fields of Java this summer by the International Rice Research Institute.
It has already been used to chemically spay 170 dogs from the Navajo Nation that were adopted to homes. Mayer and Dyer are animal lovers who say this is a good way to restore balance in animal populations gone haywire.
Commercial licensing for pet spaying is probably at least two years away, they say.
Mayer is president and Dyer is chief researcher for SenesTech, a Flagstaff biotechnology company founded in 2002 to improve women's health and control feral animal populations.
The rodents, able to produce 600 offspring from one pair in a few months, have sometimes eaten one-third of the rice crops and are raising a famine scare in India. General anti-coagulant poisons knock back the populations, but they always rebound.
"With the food shortages that are starting to erupt, this is huge," said Cheryl Dyer, researcher and ovarian physiologist at Northern Arizona University.
She and NAU scientists Loretta Mayer and Timothy Vail have helped create a product that could knock back the rat population, and nonsurgically sterilize female dogs, cats and other vertebrate pest species.
The idea might someday replace surgeries to spay domestic pets, help control packs of rabid dogs in Africa -- or find popularity in Spain, where pied pipers tried last year to drive crop-eating rodents from their fields with the use of flutes.
And if rice-growing countries were to spay rats and save 10 percent more of their crops per year, it would be enough to feed 380 million people.
The product came from the discovery that an industrial compound found in the plastics industry could accelerate the aging process in rodents, but affect no other part of the body.
"I saw it and said, 'That's my model for menopause,'" Mayer said.
Pharmaceutical companies had been testing drugs for human on mice and rats with their female reproductive organs removed.
This compound kept the organs intact, to cause chemical sterilization, more closely simulating menopause in women.
In short, it created a better lab mouse.
And the compound is short-lived, posing less environmental and food-chain risk than the anticoagulants now used to poison rice-field rats and whatever other animals consume the bait.
Rice-producing countries are currently spending more than $1 billion annually on poison, Mayer said, while chemists must continually rework the poisons to keep ahead of animal resistance.
This chemical compound, named ContraPest, is to be used in the rice fields of Java this summer by the International Rice Research Institute.
It has already been used to chemically spay 170 dogs from the Navajo Nation that were adopted to homes. Mayer and Dyer are animal lovers who say this is a good way to restore balance in animal populations gone haywire.
Commercial licensing for pet spaying is probably at least two years away, they say.
Mayer is president and Dyer is chief researcher for SenesTech, a Flagstaff biotechnology company founded in 2002 to improve women's health and control feral animal populations.
Scientists Call For More Access To Biotech Crop Data
[Source: ScienceDaily] - More than one billion acres of biotech crops have been grown in the US, but their environmental impacts are not fully known. In Arizona, farmers share maps of biotech cotton fields with University of Arizona scientists, enabling detailed analyses of the effects of this technology. Now a team of biologists proposes that making similar maps of the entire US available to scientists will permit much-needed studies of the environmental impacts of genetically engineered crops.
Biologists call for making available more detailed maps of the locations of biotech crops. Access to maps of biotech crops on a county and township level will give researchers greater ability to analyze the effects of biotech crops on wildlife, water quality, and on pest and beneficial insects.
"Since 1996 more than a billion acres have been planted with biotech crops in the U.S.," said Michelle Marvier of Santa Clara University in Calif. "We don't really know what are the pros and cons of this important new agricultural technology."
"People on both sides of the debate about genetically engineered crops have been making a lot of claims," said Marvier, an associate professor of biology and environmental studies. "One side has been saying that biotech crops reduce insecticide use, reduce tillage and therefore the erosion of top soil. People on the other side say that biotech crops could hurt native species."
The scientists' call will be published as a Policy Forum in the April 25, 2008, issue of the journal Science. Marvier's co-authors are Yves Carrière and Bruce Tabashnik of The University of Arizona in Tucson; Norman Ellstrand of the University of California at Riverside; Paul Gepts of the University of California at Davis; Peter Kareiva of Santa Clara University and The Nature Conservancy; Emma Rosi-Marshall of Loyola University in Chicago; and L. LaReesa Wolfenbarger of the University of Nebraska in Omaha.
The article, Harvesting Data from Genetically Engineered Crops, has a map showing the distribution of crop fields in Arizona township by township.
Tabashnik, UA head and professor of entomology, said, "Putting Arizona's biotech cotton on the map has allowed us to be a leader in assessing the environmental impacts of biotech crops."
In Arizona, a unique collaboration between researchers and farmers has made detailed crop data available to researchers at The University of Arizona.
Tabashnik said, "It's a win-win situation. We analyze data they collect, so they can control pests better and make more money. It helps us obtain fundamental information about what's going on in the field that we could never get without them."
One of the UA's analyses showed that adoption of biotech cotton in Arizona helped to reduce insecticide use while sustaining yields.
Carrière, a UA professor of entomology who has done many of the analyses, said, "You have to protect the privacy of the farmers. We've done it in Arizona, so why not do it across the country?"
To start examining those questions in other parts of the U.S., the team of scientists call for the government to make available data it is already collecting.
At the present time, the team writes, the U.S. Department of Agriculture collects data at the scale of individual farms, but the data are only available to researchers at the scale of entire states. Answering key questions about the environmental impacts of genetically engineered crops requires finer spatial resolution.
"The analyses could be about quality of water, quality of soil, non-target effects, regional population density of pests and economic aspects such as yield improvement," said Carrière. "The findings could be useful to a wide range of people."
The U.S. Department of Agriculture's National Agricultural Statistical Service annually collects data documenting acreage planted to various crops in all 50 states, the researchers write in their paper. In addition, the NASS annually interviews more than 125,000 farmers about their land use and the acreage planted in various biotech crops.
Tabashnik said, "We're already spending the money to have these data collected. Let's make them available in the right format for researchers to use. It would be a relatively inexpensive additional step with enormous scientific and public benefit."
Adapted from materials provided by University of Arizona, via EurekAlert!, a service of AAAS.
Biologists call for making available more detailed maps of the locations of biotech crops. Access to maps of biotech crops on a county and township level will give researchers greater ability to analyze the effects of biotech crops on wildlife, water quality, and on pest and beneficial insects.
"Since 1996 more than a billion acres have been planted with biotech crops in the U.S.," said Michelle Marvier of Santa Clara University in Calif. "We don't really know what are the pros and cons of this important new agricultural technology."
"People on both sides of the debate about genetically engineered crops have been making a lot of claims," said Marvier, an associate professor of biology and environmental studies. "One side has been saying that biotech crops reduce insecticide use, reduce tillage and therefore the erosion of top soil. People on the other side say that biotech crops could hurt native species."
The scientists' call will be published as a Policy Forum in the April 25, 2008, issue of the journal Science. Marvier's co-authors are Yves Carrière and Bruce Tabashnik of The University of Arizona in Tucson; Norman Ellstrand of the University of California at Riverside; Paul Gepts of the University of California at Davis; Peter Kareiva of Santa Clara University and The Nature Conservancy; Emma Rosi-Marshall of Loyola University in Chicago; and L. LaReesa Wolfenbarger of the University of Nebraska in Omaha.
The article, Harvesting Data from Genetically Engineered Crops, has a map showing the distribution of crop fields in Arizona township by township.
Tabashnik, UA head and professor of entomology, said, "Putting Arizona's biotech cotton on the map has allowed us to be a leader in assessing the environmental impacts of biotech crops."
In Arizona, a unique collaboration between researchers and farmers has made detailed crop data available to researchers at The University of Arizona.
Tabashnik said, "It's a win-win situation. We analyze data they collect, so they can control pests better and make more money. It helps us obtain fundamental information about what's going on in the field that we could never get without them."
One of the UA's analyses showed that adoption of biotech cotton in Arizona helped to reduce insecticide use while sustaining yields.
Carrière, a UA professor of entomology who has done many of the analyses, said, "You have to protect the privacy of the farmers. We've done it in Arizona, so why not do it across the country?"
To start examining those questions in other parts of the U.S., the team of scientists call for the government to make available data it is already collecting.
At the present time, the team writes, the U.S. Department of Agriculture collects data at the scale of individual farms, but the data are only available to researchers at the scale of entire states. Answering key questions about the environmental impacts of genetically engineered crops requires finer spatial resolution.
"The analyses could be about quality of water, quality of soil, non-target effects, regional population density of pests and economic aspects such as yield improvement," said Carrière. "The findings could be useful to a wide range of people."
The U.S. Department of Agriculture's National Agricultural Statistical Service annually collects data documenting acreage planted to various crops in all 50 states, the researchers write in their paper. In addition, the NASS annually interviews more than 125,000 farmers about their land use and the acreage planted in various biotech crops.
Tabashnik said, "We're already spending the money to have these data collected. Let's make them available in the right format for researchers to use. It would be a relatively inexpensive additional step with enormous scientific and public benefit."
Adapted from materials provided by University of Arizona, via EurekAlert!, a service of AAAS.
Thursday, April 24, 2008
Human beings may have had a brush with extinction 70,000 years ago, an extensive genetic study suggests.
[Source: CNN] - The human population at that time was reduced to small isolated groups in Africa, apparently because of drought, according to an analysis released Thursday.
The report notes that a separate study by researchers at Stanford University estimated the number of early humans may have shrunk as low as 2,000 before numbers began to expand again in the early Stone Age.
"This study illustrates the extraordinary power of genetics to reveal insights into some of the key events in our species' history," Spencer Wells, National Geographic Society explorer in residence, said in a statement.
"Tiny bands of early humans, forced apart by harsh environmental conditions, coming back from the brink to reunite and populate the world. Truly an epic drama, written in our DNA."
Wells is director of the Genographic Project, launched in 2005 to study anthropology using genetics. The report was published in the American Journal of Human Genetics.
Previous studies using mitochondrial DNA -- which is passed down through mothers -- have traced modern humans to a single "mitochondrial Eve," who lived in Africa about 200,000 years ago.
The migrations of humans out of Africa to populate the rest of the world appear to have begun about 60,000 years ago, but little has been known about humans between Eve and that dispersal.
Genographic Project
The new study looks at the mitochondrial DNA of the Khoi and San people in South Africa, who appear to have diverged from other people between 90,000 and 150,000 years ago.
The researchers led by Doron Behar of Rambam Medical Center in Haifa, Israel, and Saharon Rosset of IBM T.J. Watson Research Center in Yorktown Heights, New York, and Tel Aviv University concluded that humans separated into small populations before the Stone Age, when they came back together and began to increase in numbers and spread to other areas.
Eastern Africa experienced a series of severe droughts between 135,000 and 90,000 years ago, and researchers said this climatological shift may have contributed to the population changes, dividing into small, isolated groups that developed independently.
Paleontologist Meave Leakey, a Genographic adviser, said: "Who would have thought that as recently as 70,000 years ago, extremes of climate had reduced our population to such small numbers that we were on the very edge of extinction?"
Today, more than 6.6 billion people inhabit the globe, according to the U.S. Census Bureau.
The research was funded by the National Geographic Society, IBM, the Waitt Family Foundation, the Seaver Family Foundation, Family Tree DNA and Arizona Research Labs.
The report notes that a separate study by researchers at Stanford University estimated the number of early humans may have shrunk as low as 2,000 before numbers began to expand again in the early Stone Age.
"This study illustrates the extraordinary power of genetics to reveal insights into some of the key events in our species' history," Spencer Wells, National Geographic Society explorer in residence, said in a statement.
"Tiny bands of early humans, forced apart by harsh environmental conditions, coming back from the brink to reunite and populate the world. Truly an epic drama, written in our DNA."
Wells is director of the Genographic Project, launched in 2005 to study anthropology using genetics. The report was published in the American Journal of Human Genetics.
Previous studies using mitochondrial DNA -- which is passed down through mothers -- have traced modern humans to a single "mitochondrial Eve," who lived in Africa about 200,000 years ago.
The migrations of humans out of Africa to populate the rest of the world appear to have begun about 60,000 years ago, but little has been known about humans between Eve and that dispersal.
Genographic Project
The new study looks at the mitochondrial DNA of the Khoi and San people in South Africa, who appear to have diverged from other people between 90,000 and 150,000 years ago.
The researchers led by Doron Behar of Rambam Medical Center in Haifa, Israel, and Saharon Rosset of IBM T.J. Watson Research Center in Yorktown Heights, New York, and Tel Aviv University concluded that humans separated into small populations before the Stone Age, when they came back together and began to increase in numbers and spread to other areas.
Eastern Africa experienced a series of severe droughts between 135,000 and 90,000 years ago, and researchers said this climatological shift may have contributed to the population changes, dividing into small, isolated groups that developed independently.
Paleontologist Meave Leakey, a Genographic adviser, said: "Who would have thought that as recently as 70,000 years ago, extremes of climate had reduced our population to such small numbers that we were on the very edge of extinction?"
Today, more than 6.6 billion people inhabit the globe, according to the U.S. Census Bureau.
The research was funded by the National Geographic Society, IBM, the Waitt Family Foundation, the Seaver Family Foundation, Family Tree DNA and Arizona Research Labs.
UA Researchers Tackling Unsolved Questions about Protein Structures
[Source: Deborah Dawn, BIO5] - A University of Arizona research team is exploring the evolutionary origins of protein structures. Their findings help us better understand how proteins evolved to carry out the instructions encoded in the genes of every living thing.
Protein molecules are made up of chains of amino acids. These chains bend and fold into a dizzying array of three-dimensional shapes and structures, depending on the order of the amino acids in a given chain. Those varied structures are part of what allow the proteins—which are assembled based on instructions coded in DNA—to regulate everything from an organism's growth and metabolism to the ways messages are transmitted from cell to cell. Protein structures are at the heart of how organisms function.
However, the evolution of those structures is still poorly understood, because there are few observed examples of proteins that have clearly evolved from one shape to another. "The origin of the diversity of protein structures is a major unsolved problem," explains BIO5 member Matthew H.J. Cordes, an associate professor of Biochemistry and Molecular Biophysics at the UA.
Cordes' lab is solving that problem. Two graduate students in his lab, Christian M. Roessler and Branwen M. Hall, have located protein molecules in two different viruses that have dramatically different structures: one protein has a helical, or corkscrew shape, while the other is shaped more like a hairpin. Yet these very different proteins have similar amino acid sequences and perform similar functions--binding to DNA to help the viruses replicate and spread--making it likely that they had a common ancestor.
"Somehow, mutations converted the corkscrew structure to the hairpin structure," Cordes says of the finding, which was recently reported in the Proceedings of the National Academy of Sciences.
While this isn't the first example of structural differences among proteins with a common ancestor, it may be the most dramatic natural example of related proteins retaining clear similarity in amino acid sequence while undergoing major reorganization of their structure. "This finding strongly confirms that evolutionary processes produce new protein shapes," Cordes says. "It could become a textbook example of the reality and beauty of evolutionary changes in structure." He adds that some proteins in this family with the hairpin shape bind to DNA more strongly than those with the corkscrew shape, though it is too early to tell if this is always the case. It's not yet known whether such an advantage helped drive the hairpin structure's evolution.
Cordes' graduate students found their protein pair via an unusual method: Roessler and Hall used a stepping-stone technique to make a series of small "jumps" among closely related proteins, following minute structural changes from one protein to another until they "landed" at a protein that was dramatically different from the one they'd started with, yet was still related to it.
Cordes' lab is now working out the details of the specific mutations that might have caused their two proteins to diverge from one another. They also plan to use their stepping-stone technique to shed light on the evolutionary links among other proteins.
"This is like space exploration," Cordes says. "We're journeying through the protein universe, step by step."
Tuesday, April 22, 2008
Texas cancer center eyes Valley connection
[Source; Kate Nolan, Arizona Republic] - It's not unusual to find a cancer event in the Northeast Valley.
Scottsdale boasts branches of the Arizona Cancer Center (based in Tucson) and the Mayo Clinic Cancer Center (based in Rochester, Minn.).
Both are among the 39 elite comprehensive cancer centers funded by the National Cancer Institute, and they dependably capture the attention of local donors. Arizona Cancer Center is said to be the national leader in cancer prevention.
What was unusual about a recent cancer promotion held at Camelback Golf Club in Scottsdale, was its focus: the University of Texas M.D. Anderson Cancer Center in Houston.
Party hosts were part-time Paradise Valley residents Jo Ann and Paul Oreffice. He is the retired chairman of Dow Chemical Co., and said he wanted to raise the community's awareness of M.D. Anderson. Oreffice's son-in-law was treated successfully there for a brain tumor that Portland doctors said was untreatable.
"He hasn't had a bad day in eight-and-a-half years," said Oreffice, who serves on a philanthropic board at M.D. Anderson and is President of the National Parkinson Foundation.
One of the nation's oldest and largest cancer centers, M.D. Anderson oversees around a half-billion dollars in research projects every year and a total annual budget of $2.8 billion. The place is so vast, it isn't known for any one specialty.
M.D. Anderson welcomes private contributions from anywhere, but usually seeks support in areas closer to home, as most health institutions do, said a spokeswoman.
Similarly, most of Mayo Clinic Arizona's donations come from Arizona.
Why is M.D. Anderson here?
Would Mayo throw a promotional party in Houston where major institutions already exist?
Probably not, said Dr. Susan Dolbert, Mayo development chairman in Arizona.
But M.D. Anderson may have its reasons: the Texas center appears to be enlisting in the Valley's war on cancer.
Not long ago, an extensive downtown Phoenix cancer center was on the drawing boards.
At first, there was talk of collaboration between Arizona Cancer Center, Maricopa Medical Center, Scottsdale Healthcare, Banner Health and others for a downtown facility in conjunction with the University of Arizona College of Medicine.
Then came talks between the Arizona Cancer Center and Banner Health, Arizona's largest healthcare provider.
But last year, the conversations faded with no end-product.
Possible new cancer partnership
Now the talk is back on, between M.D. Anderson and Banner Health, according to sources from both institutions.
"A number of cities are talking with us," said Dr. John Mendelsohn, the Texas center's president, somewhat minimizing the Phoenix talks.
Mendelsohn said M.D. Anderson is following the Mayo Clinic expansion model, but on a global scale, with centers in Madrid and Orlando and that his cancer center already collaborates with Arizona Cancer Center on several initiatives.
Banner spokesman Bill Byron said, "A metropolitan area this size needs a comprehensive cancer center. We anticipate the discussions will result in one and are still exploring options."
Byron declined to comment on details or other possible partners, but said the list of potential partners for such an undertaking is limited.
Ultimately, senior leadership will make Banner's call. The Texans have been less forthcoming.
As for the golf clubhouse meet-and-greet, M.D. Anderson spokeswoman DeDe DeStefano maintained, "Truly, it was unrelated to the talks."
Scottsdale boasts branches of the Arizona Cancer Center (based in Tucson) and the Mayo Clinic Cancer Center (based in Rochester, Minn.).
Both are among the 39 elite comprehensive cancer centers funded by the National Cancer Institute, and they dependably capture the attention of local donors. Arizona Cancer Center is said to be the national leader in cancer prevention.
What was unusual about a recent cancer promotion held at Camelback Golf Club in Scottsdale, was its focus: the University of Texas M.D. Anderson Cancer Center in Houston.
Party hosts were part-time Paradise Valley residents Jo Ann and Paul Oreffice. He is the retired chairman of Dow Chemical Co., and said he wanted to raise the community's awareness of M.D. Anderson. Oreffice's son-in-law was treated successfully there for a brain tumor that Portland doctors said was untreatable.
"He hasn't had a bad day in eight-and-a-half years," said Oreffice, who serves on a philanthropic board at M.D. Anderson and is President of the National Parkinson Foundation.
One of the nation's oldest and largest cancer centers, M.D. Anderson oversees around a half-billion dollars in research projects every year and a total annual budget of $2.8 billion. The place is so vast, it isn't known for any one specialty.
M.D. Anderson welcomes private contributions from anywhere, but usually seeks support in areas closer to home, as most health institutions do, said a spokeswoman.
Similarly, most of Mayo Clinic Arizona's donations come from Arizona.
Why is M.D. Anderson here?
Would Mayo throw a promotional party in Houston where major institutions already exist?
Probably not, said Dr. Susan Dolbert, Mayo development chairman in Arizona.
But M.D. Anderson may have its reasons: the Texas center appears to be enlisting in the Valley's war on cancer.
Not long ago, an extensive downtown Phoenix cancer center was on the drawing boards.
At first, there was talk of collaboration between Arizona Cancer Center, Maricopa Medical Center, Scottsdale Healthcare, Banner Health and others for a downtown facility in conjunction with the University of Arizona College of Medicine.
Then came talks between the Arizona Cancer Center and Banner Health, Arizona's largest healthcare provider.
But last year, the conversations faded with no end-product.
Possible new cancer partnership
Now the talk is back on, between M.D. Anderson and Banner Health, according to sources from both institutions.
"A number of cities are talking with us," said Dr. John Mendelsohn, the Texas center's president, somewhat minimizing the Phoenix talks.
Mendelsohn said M.D. Anderson is following the Mayo Clinic expansion model, but on a global scale, with centers in Madrid and Orlando and that his cancer center already collaborates with Arizona Cancer Center on several initiatives.
Banner spokesman Bill Byron said, "A metropolitan area this size needs a comprehensive cancer center. We anticipate the discussions will result in one and are still exploring options."
Byron declined to comment on details or other possible partners, but said the list of potential partners for such an undertaking is limited.
Ultimately, senior leadership will make Banner's call. The Texans have been less forthcoming.
As for the golf clubhouse meet-and-greet, M.D. Anderson spokeswoman DeDe DeStefano maintained, "Truly, it was unrelated to the talks."
Experts get $6.6 mil for Alzheimer's work
[Source: Ken Alltucker, The Arizona Republic] - Scientists at Banner Alzheimer's Institute and the Mayo Clinic in Arizona have secured a $6.6 million federal grant to study the brains of people who carry a genetic risk for developing Alzheimer's disease.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
Monday, April 21, 2008
Mighty Microbes: Bacteria Filaments Can Bundle Together And Move Objects 100,000 Times Bacterium's Body Weight
[Source:ScienceDaily] - Researchers from The University of Arizona and Columbia University have discovered that tiny filaments on bacteria can bundle together and pull with forces far stronger than experts had previously thought possible.
The team of researchers, including Magdalene "Maggie" So, a member of the BIO5 Institute and the department of immunobiology in the UA College of Medicine, studied Type IV pili -- or filaments -- on the surface of Neisseria gonorrhoeae, the bacterium that causes the infectious disease gonorrhea. The research results help them understand the role that Type IV pili play in initiating a variety of infectious diseases -- including tuberculosis -- and how retracting pili allow bacteria to crawl and to exchange genes with each other.
When a bundle of Type IV pili retracts, it pulls with a force in the nanoNewton range, which is 10 times the force of a single retracting filament. The study demonstrates the power and cooperative nature of the nanomotors that cause Type IV pili to retract.
"The motor that causes these filaments to pull is one of the strongest nanomotors known in biology," So said.
In previous studies, the same group of investigators measured single filament retraction forces in the 50 to 100 picoNewton range. This force allows the bacterium to move an object 10,000 times its own body weight. Retraction forces from a bundle are roughly 10 times higher, allowing the bacterium to move objects 100,000 times its body weight.
Pilus retraction forces are an important factor in how N. gonorrhoeae starts an infection. So, who has studied these microbes for more than 20 years, says N. gonorrhoeae communicates with a human cell by pulling on it. These pulling forces perturb the normal circuitry of the cell. As a result, the infected cell is fooled into lowering its defenses against the infecting microbe.
So said that the team of investigators came up with a new method to measure the tremendous forces applied by retracting pili. They allow bacteria to sit on a dense brushwork of tiny elastic pillars. The pili attach to these pillars. When pili retract, they bend the pillars. By measuring how the pillars bend, the investigators calculate the retraction forces.
An article about the research, titled "Cooperative Retraction of Bundled Type IV Pili Enables Nanonewton Force Generation," was published in the latest issue of PLoS Biology.
Authors of the PLoS Biology article are Nicolas Biais and Mike Sheetz, Columbia University; Benoit Ladoux, Université Paris 7; So and Dustin Higashi, both from the UA.
Adapted from materials provided by University of Arizona.
The team of researchers, including Magdalene "Maggie" So, a member of the BIO5 Institute and the department of immunobiology in the UA College of Medicine, studied Type IV pili -- or filaments -- on the surface of Neisseria gonorrhoeae, the bacterium that causes the infectious disease gonorrhea. The research results help them understand the role that Type IV pili play in initiating a variety of infectious diseases -- including tuberculosis -- and how retracting pili allow bacteria to crawl and to exchange genes with each other.
When a bundle of Type IV pili retracts, it pulls with a force in the nanoNewton range, which is 10 times the force of a single retracting filament. The study demonstrates the power and cooperative nature of the nanomotors that cause Type IV pili to retract.
"The motor that causes these filaments to pull is one of the strongest nanomotors known in biology," So said.
In previous studies, the same group of investigators measured single filament retraction forces in the 50 to 100 picoNewton range. This force allows the bacterium to move an object 10,000 times its own body weight. Retraction forces from a bundle are roughly 10 times higher, allowing the bacterium to move objects 100,000 times its body weight.
Pilus retraction forces are an important factor in how N. gonorrhoeae starts an infection. So, who has studied these microbes for more than 20 years, says N. gonorrhoeae communicates with a human cell by pulling on it. These pulling forces perturb the normal circuitry of the cell. As a result, the infected cell is fooled into lowering its defenses against the infecting microbe.
So said that the team of investigators came up with a new method to measure the tremendous forces applied by retracting pili. They allow bacteria to sit on a dense brushwork of tiny elastic pillars. The pili attach to these pillars. When pili retract, they bend the pillars. By measuring how the pillars bend, the investigators calculate the retraction forces.
An article about the research, titled "Cooperative Retraction of Bundled Type IV Pili Enables Nanonewton Force Generation," was published in the latest issue of PLoS Biology.
Authors of the PLoS Biology article are Nicolas Biais and Mike Sheetz, Columbia University; Benoit Ladoux, Université Paris 7; So and Dustin Higashi, both from the UA.
Adapted from materials provided by University of Arizona.
Scientists Explore Human Gene Pool With Help From Microsoft Research
[Source: Microsoft Corp.] - Projects show potential of computer science to profoundly impact prediction and treatment of genetic diseases.
Breakthrough research with the ability to predict and prevent adverse drug responses within prescription medicine, and provide greater insight into the cause of neurodegenerative illnesses such as Parkinson's disease and Alzheimer's disease, are just two of six research projects Microsoft Research today announced it will support through its Computational Challenges of Genome Wide Association Studies (GWAS) program.
The supported projects were selected from 40 proposals submitted from 39 academic institutions worldwide. Microsoft Research's goal with funding computational challenges associated with GWAS research is to aid researchers in the correlation of genetic patterns with patients' responses to drugs, diseases, aging or the expression of genetic disorders. The ultimate goal is to enable lifesaving research through the use of technology.
"The Microsoft Research GWAS program provides crucial funding at the interface between information management and quality healthcare," said Michael Kane, an assistant professor of Computer Technology at Purdue University and one of the researchers selected to receive support under the GWAS program. "Patient-specific genotyping to assure prescription drug safety and drug effectiveness is a major step toward the emergence and adoption of personalized medicine, and this support is key to facilitating that vision. Microsoft Corp. has recognized the important role information technology will play in the future of healthcare. Ultimately, this is about technology that helps to save lives."
As part of the program, more than $850,000 was shared among six research institutions.
"When it comes to performing genetic analysis, researchers are often hampered by the data itself, whether it's inconsistencies in format, the inability to visualize it, or sheer volume," said Kristin Tolle, program manager for biomedical computing on the External Research & Programs (ER&P) team at Microsoft Research. "Through this program, Microsoft Research is encouraging the development of computer-science solutions to improve data access, standardization, visualization and tools to help scientists study the human genome. "Of all the research areas Microsoft collaborates with, none may have as much real impact on global economies and the lives of ordinary people as healthcare," Tolle said.
Enabling this research is part of ER&P's broader efforts to move research in new directions across nearly every field of computer science, engineering and general science. Through this and other regional and global programs, Microsoft Research is partnering with researchers and scientists to address some of the toughest, most urgent scientific and societal challenges -- such as those in healthcare -- through enabling technologies that can provide real solutions.
Other examples of Microsoft's support of healthcare-related research include the program Cell Phones as a Platform for Healthcare, which sought novel healthcare solutions that are accessible, affordable and relevant for smart mobile phones; and the Intelligent Systems for Assisted Cognition Awards, which provided funding for technologies to assist people living with disorders such as autism and Alzheimer's disease. In the past six months alone, Microsoft External Research & Programs has awarded more than $2.5 million to academic researchers and scientists in support of healthcare research.
John Pearson is one of the six winners and a description of the project follows:
Translational Genomics Research Institute, John Pearson: "A Universal Data Format for Genotype Microarrays." Combining data generated in genome research is problematic due to the variety of software platforms in use today. Pearson will work to create a universal data format that would accommodate multiple vendor platforms into a single file and software library. The software library would allow for open use by the research community and commercial proprietary use by platform vendors.
Breakthrough research with the ability to predict and prevent adverse drug responses within prescription medicine, and provide greater insight into the cause of neurodegenerative illnesses such as Parkinson's disease and Alzheimer's disease, are just two of six research projects Microsoft Research today announced it will support through its Computational Challenges of Genome Wide Association Studies (GWAS) program.
The supported projects were selected from 40 proposals submitted from 39 academic institutions worldwide. Microsoft Research's goal with funding computational challenges associated with GWAS research is to aid researchers in the correlation of genetic patterns with patients' responses to drugs, diseases, aging or the expression of genetic disorders. The ultimate goal is to enable lifesaving research through the use of technology.
"The Microsoft Research GWAS program provides crucial funding at the interface between information management and quality healthcare," said Michael Kane, an assistant professor of Computer Technology at Purdue University and one of the researchers selected to receive support under the GWAS program. "Patient-specific genotyping to assure prescription drug safety and drug effectiveness is a major step toward the emergence and adoption of personalized medicine, and this support is key to facilitating that vision. Microsoft Corp. has recognized the important role information technology will play in the future of healthcare. Ultimately, this is about technology that helps to save lives."
As part of the program, more than $850,000 was shared among six research institutions.
"When it comes to performing genetic analysis, researchers are often hampered by the data itself, whether it's inconsistencies in format, the inability to visualize it, or sheer volume," said Kristin Tolle, program manager for biomedical computing on the External Research & Programs (ER&P) team at Microsoft Research. "Through this program, Microsoft Research is encouraging the development of computer-science solutions to improve data access, standardization, visualization and tools to help scientists study the human genome. "Of all the research areas Microsoft collaborates with, none may have as much real impact on global economies and the lives of ordinary people as healthcare," Tolle said.
Enabling this research is part of ER&P's broader efforts to move research in new directions across nearly every field of computer science, engineering and general science. Through this and other regional and global programs, Microsoft Research is partnering with researchers and scientists to address some of the toughest, most urgent scientific and societal challenges -- such as those in healthcare -- through enabling technologies that can provide real solutions.
Other examples of Microsoft's support of healthcare-related research include the program Cell Phones as a Platform for Healthcare, which sought novel healthcare solutions that are accessible, affordable and relevant for smart mobile phones; and the Intelligent Systems for Assisted Cognition Awards, which provided funding for technologies to assist people living with disorders such as autism and Alzheimer's disease. In the past six months alone, Microsoft External Research & Programs has awarded more than $2.5 million to academic researchers and scientists in support of healthcare research.
John Pearson is one of the six winners and a description of the project follows:
Translational Genomics Research Institute, John Pearson: "A Universal Data Format for Genotype Microarrays." Combining data generated in genome research is problematic due to the variety of software platforms in use today. Pearson will work to create a universal data format that would accommodate multiple vendor platforms into a single file and software library. The software library would allow for open use by the research community and commercial proprietary use by platform vendors.
Thursday, April 17, 2008
No stopping stem cells
[Source: BEN NORRIS, Arizona Daily Sun] - A renowned scholar and advocate for stem cell research took the stage of the High Country Conference Center Saturday to preach the benefits of embryonic stem cell treatment.
Christopher Scott, a Stanford University researcher and author, has spent much of the past decade studying both the scientific and ethical issues surrounding the controversial topic. "This issue becomes so polarizing," Scott said. "It just drives the wedge deeper. The point of this should be to open the door and get everyone's point of view. We need good, pragmatic people."
Scott was the keynote speaker at a conference of honors college students from throughout the western U.S.
Booking the scholar is quite a feat for NAU and the new conference center. Scott's work has been featured on NPR's Science Friday program and has earned him a coveted fellowship at King's College in London.
Scott has given more than 50 talks at colleges and conferences throughout the country, explaining his position and promoting his 2007 book "Stem Cells Now." Controversy surrounds the stem cells scientists wish to use, taken from embryos donated by potential mothers for in vitro fertilization.
Scott said many of these embryos are simply discarded after a few months of going unused because potential parents tend to donate more than is necessary.
"This raises important ethical and political questions," Scott said. "Should we let them go or should we use them for public benefit."
The argument is most heated between two factions: those who believe life begins with the embryo and those who believe the embryo is basically a collection of cells.
"An important topic is whether a 2-day-old embryo is human," Scott said. "Most scholars and ethicists have moved beyond that discussion. It will be very hard to meet in the middle. If you think it is murder, there is no middle ground."
Indeed, Scott admits he has come across some pretty fierce opposition from right-to-life groups, but always tries to keep the conversations civil. He faced no public opposition during his presentation at the conference center Saturday.
ON THE EDGES OF MEDICINE
During his presentation, Scott showed the audience slides of bladders and kidneys reshaped with the help of stem cell technology.
Scott said the first embryonic stem cell clinical trials in the United States are slated to begin in the next three months. Researchers and medical professionals plan to attempt a stem cell transplant to treat spinal injuries.
Scot said researchers are also interested to learn if using stem cells can reverse or slow the progress of macular degeneration, a condition that eventually leads to blindness.
Scientists also believe stem cell research can lead to the regeneration of heart, liver, kidney and muscle cells, to name a few.
"This is now a world phenomenon," Scott said. "The U.S. is one of dozens of countries doing this research."
Although the United States government prohibits federal funding of all but a few stem cell lines, research is not prohibited in all 50 states.
CONFERENCE A PLATFORM FOR STUDENTS, TOO
The weekend-long conference, hosted by NAU and the High Country Conference Center, brought honors students from more than 40 colleges and universities throughout the western United States.
Students had a chance to present their own research during breakout sessions. Topics ranged from discussions in bioscience to history and political issues.
"This is a great experience for the audience and the presenters," said Michael Evertson, a sophomore from Central Arizona College, who gave his presentation on the history of progressive rock music. "I came to enjoy the presentations and make some networking connections."
Kelly Lintecum, also a sophomore at the same college, gave her presentation on avian flu. She hopes to study bioscience at either NAU or ASU, but has not made up her mind just yet.
"I'm here to improve my public speaking skills," Lintecum said. "It's also important to represent my school."
Honor students from NAU also made sure to show up for the event. Zeke Lihosit, a freshman history major volunteered to help with the organization and setup, not to mention testing the waters for a presentation of his own next time the conference rolls around.
"This is my first time at a conference like this," Lihosit said. "It's pretty cool to see all these students present their ideas and research."
This is the first major conference at the center to host guests from all over the western United States.
Stem Cell Research Quick Hits
- Stem cell research is a misdemeanor crime in the state of South Dakota
- Researchers are ready to treat spinal injuries and blindness in the first phases of stem cell treatment.
- Stanford researchers used embryonic stem cells to create a mouse whose brain was 1 percent human.
- Despite legislation prohibiting federal funding, Californians approved a bill in 2007 granting the use of state funds to finance research.
- Scientists used stem cell research and tissue regeneration to create a replica kidney roughly the size of a 50-cent piece.
- Adult stem cells can be found in the stomach, blood, skin and in sperm
Source: Christopher Scott, Stanford University researcher
Christopher Scott, a Stanford University researcher and author, has spent much of the past decade studying both the scientific and ethical issues surrounding the controversial topic. "This issue becomes so polarizing," Scott said. "It just drives the wedge deeper. The point of this should be to open the door and get everyone's point of view. We need good, pragmatic people."
Scott was the keynote speaker at a conference of honors college students from throughout the western U.S.
Booking the scholar is quite a feat for NAU and the new conference center. Scott's work has been featured on NPR's Science Friday program and has earned him a coveted fellowship at King's College in London.
Scott has given more than 50 talks at colleges and conferences throughout the country, explaining his position and promoting his 2007 book "Stem Cells Now." Controversy surrounds the stem cells scientists wish to use, taken from embryos donated by potential mothers for in vitro fertilization.
Scott said many of these embryos are simply discarded after a few months of going unused because potential parents tend to donate more than is necessary.
"This raises important ethical and political questions," Scott said. "Should we let them go or should we use them for public benefit."
The argument is most heated between two factions: those who believe life begins with the embryo and those who believe the embryo is basically a collection of cells.
"An important topic is whether a 2-day-old embryo is human," Scott said. "Most scholars and ethicists have moved beyond that discussion. It will be very hard to meet in the middle. If you think it is murder, there is no middle ground."
Indeed, Scott admits he has come across some pretty fierce opposition from right-to-life groups, but always tries to keep the conversations civil. He faced no public opposition during his presentation at the conference center Saturday.
ON THE EDGES OF MEDICINE
During his presentation, Scott showed the audience slides of bladders and kidneys reshaped with the help of stem cell technology.
Scott said the first embryonic stem cell clinical trials in the United States are slated to begin in the next three months. Researchers and medical professionals plan to attempt a stem cell transplant to treat spinal injuries.
Scot said researchers are also interested to learn if using stem cells can reverse or slow the progress of macular degeneration, a condition that eventually leads to blindness.
Scientists also believe stem cell research can lead to the regeneration of heart, liver, kidney and muscle cells, to name a few.
"This is now a world phenomenon," Scott said. "The U.S. is one of dozens of countries doing this research."
Although the United States government prohibits federal funding of all but a few stem cell lines, research is not prohibited in all 50 states.
CONFERENCE A PLATFORM FOR STUDENTS, TOO
The weekend-long conference, hosted by NAU and the High Country Conference Center, brought honors students from more than 40 colleges and universities throughout the western United States.
Students had a chance to present their own research during breakout sessions. Topics ranged from discussions in bioscience to history and political issues.
"This is a great experience for the audience and the presenters," said Michael Evertson, a sophomore from Central Arizona College, who gave his presentation on the history of progressive rock music. "I came to enjoy the presentations and make some networking connections."
Kelly Lintecum, also a sophomore at the same college, gave her presentation on avian flu. She hopes to study bioscience at either NAU or ASU, but has not made up her mind just yet.
"I'm here to improve my public speaking skills," Lintecum said. "It's also important to represent my school."
Honor students from NAU also made sure to show up for the event. Zeke Lihosit, a freshman history major volunteered to help with the organization and setup, not to mention testing the waters for a presentation of his own next time the conference rolls around.
"This is my first time at a conference like this," Lihosit said. "It's pretty cool to see all these students present their ideas and research."
This is the first major conference at the center to host guests from all over the western United States.
Stem Cell Research Quick Hits
- Stem cell research is a misdemeanor crime in the state of South Dakota
- Researchers are ready to treat spinal injuries and blindness in the first phases of stem cell treatment.
- Stanford researchers used embryonic stem cells to create a mouse whose brain was 1 percent human.
- Despite legislation prohibiting federal funding, Californians approved a bill in 2007 granting the use of state funds to finance research.
- Scientists used stem cell research and tissue regeneration to create a replica kidney roughly the size of a 50-cent piece.
- Adult stem cells can be found in the stomach, blood, skin and in sperm
Source: Christopher Scott, Stanford University researcher
UA 'home run' is hit vs. cancer of colon
[Source: Carla McClain, Arizona Daily Star] - Striking a major blow against a top killer — colon cancer — a new drug therapy cuts the threat of this disease by as much as 90 percent in high-risk patients, University of Arizona scientists announced Monday.
The new therapy — combining the drug DFMO and an anti-inflammatory known as sulindac — was tested in patients who had developed precancerous colon polyps, putting them at high risk for full-fledged colon cancer.
Overall, their likelihood of developing more dangerous polyps was cut by 70 percent after three years on the combination therapy.
But in the most threatened patients — those who had large or multiple polyps — the risk of recurrence was slashed by a stunning 95 percent. That is more than double the preventive effect of other known therapies against colon cancer, including aspirin.
"This has really hit a home run," said Dr. David S. Alberts, director of the Arizona Cancer Center, where about 50 of the 300 patients in the study were tested and where much of the basic research and patient analysis was conducted.
"It is by a long shot the most effective therapy we have found to prevent this cancer, with very little toxicity," Alberts said.
In a cautionary note, researchers warned that the DFMO-sulindac therapy faces at least two more years of clinical trials before it will be "ready for prime-time" use in the United States.
"Although the five clinical trials we have completed show this therapy to be no more toxic than plain aspirin, we are always concerned about that issue and want further testing before this goes to the general population," said Eugene Gerner, director of the UA Cancer Center's gastrointestinal cancer program.
Gerner is the study's co-investigator, teaming with Dr. Frank Meyskens, director of the Chao Family Cancer Center at the University of California at Irvine and a former University of Arizona cancer researcher.
Their results won high praise when presented Monday at the annual meeting of the American Association for Cancer Research in San Diego.
Calling the findings "spectacular," Michael Sporn, pharmacology and toxicology professor at Dartmouth Medical School, said they "represent a landmark advance in efforts to stop the current worldwide epidemic of cancer deaths."
Colon cancer — the second-worst cancer killer in the United States — strikes nearly 150,000 Americans every year and kills about 60,000. Only lung cancer kills more.
In recent years, scientists have hurled a myriad of agents — drugs, vitamins and minerals — at high-risk patients, trying to stop colon polyps from recurring after being surgically removed.
But the results have been mixed and often conflicting. Among the most promising therapies, aspirin appears to cut polyp regrowth by slightly less than 30 percent. Celecoxib (brand name Celebrex) — an NSAID, or non-steroidal anti-inflammatory drug, similar to sulindac — has shown a 40 percent risk reduction, but it carries cardiovascular risks. The mineral calcium has at best reduced regrowth by about 20 percent.
The DFMO-sulindac combination more than doubled those rates in some cases and was especially powerful in preventing advanced polyps most likely to lead to cancer.
"That's the real breakthrough," Gerner said. "We have shown for the first time that a combination strategy can dramatically reduce this threat for the patients at highest risk.
"Further testing will tell us if this therapy might be useful for others at risk — those who have a family history of colon cancer, but have not yet developed polyps," Gerner added.
One of the key drugs in the new therapy — DFMO, or difluoromethylornithine — is a synthetic amino acid known to interfere with the carcinogenic process. But used alone, it proved toxic at doses needed for treating advanced cancer. By combining it with the NSAID sulindac, the research team was able to cut the DFMO to one-fiftieth of that dose, all but eliminating toxic effects.
"There is a great hope that we will be able to prevent colon cancer effectively using this method," Meyskens said. "We had not been able to do this before due to the high toxicity of available therapies."
The study involved about 300 patients who had at least one colon polyp within the previous five years. They were given either the daily combination DFMO (500 milligrams) and sulindac (150 mg), or a placebo.
After three years, the risk of a recurrent polyp dropped from 41.1 percent in the placebo group to 12.3 percent with treatment — a 70 percent reduction.
Even more striking, the risk in patients with advanced polyps dropped from 8.5 percent in the placebo group to 0.7 percent in the treatment group — a 92 percent reduction.
And for those in the most danger — patients with multiple previous polyps — the rate of re-growth plunged from 13.2 percent in the placebo group to 0.7 percent in the treatment group — a 95 percent reduction.
The results were so dramatic that the trial was stopped early and the results released.
Finally, an analysis of side effects and toxicity found no significant difference between the treatment and placebo groups.
The study was funded in part by the National Cancer Institute's Specialized Program of Research Excellence in GI Cancers.
The Arizona Cancer Center is one of only five institutions nationwide to receive a GI SPORE grant. Originally funded in 2002, it is the largest new grant awarded to the University of Arizona College of Medicine in the past 10 years. It was renewed in 2007 for another five years and funded at $12 million.
On StarNet: Find more cancer resources, including information on screening and prevention, at go.azstarnet.com/cancer.
The new therapy — combining the drug DFMO and an anti-inflammatory known as sulindac — was tested in patients who had developed precancerous colon polyps, putting them at high risk for full-fledged colon cancer.
Overall, their likelihood of developing more dangerous polyps was cut by 70 percent after three years on the combination therapy.
But in the most threatened patients — those who had large or multiple polyps — the risk of recurrence was slashed by a stunning 95 percent. That is more than double the preventive effect of other known therapies against colon cancer, including aspirin.
"This has really hit a home run," said Dr. David S. Alberts, director of the Arizona Cancer Center, where about 50 of the 300 patients in the study were tested and where much of the basic research and patient analysis was conducted.
"It is by a long shot the most effective therapy we have found to prevent this cancer, with very little toxicity," Alberts said.
In a cautionary note, researchers warned that the DFMO-sulindac therapy faces at least two more years of clinical trials before it will be "ready for prime-time" use in the United States.
"Although the five clinical trials we have completed show this therapy to be no more toxic than plain aspirin, we are always concerned about that issue and want further testing before this goes to the general population," said Eugene Gerner, director of the UA Cancer Center's gastrointestinal cancer program.
Gerner is the study's co-investigator, teaming with Dr. Frank Meyskens, director of the Chao Family Cancer Center at the University of California at Irvine and a former University of Arizona cancer researcher.
Their results won high praise when presented Monday at the annual meeting of the American Association for Cancer Research in San Diego.
Calling the findings "spectacular," Michael Sporn, pharmacology and toxicology professor at Dartmouth Medical School, said they "represent a landmark advance in efforts to stop the current worldwide epidemic of cancer deaths."
Colon cancer — the second-worst cancer killer in the United States — strikes nearly 150,000 Americans every year and kills about 60,000. Only lung cancer kills more.
In recent years, scientists have hurled a myriad of agents — drugs, vitamins and minerals — at high-risk patients, trying to stop colon polyps from recurring after being surgically removed.
But the results have been mixed and often conflicting. Among the most promising therapies, aspirin appears to cut polyp regrowth by slightly less than 30 percent. Celecoxib (brand name Celebrex) — an NSAID, or non-steroidal anti-inflammatory drug, similar to sulindac — has shown a 40 percent risk reduction, but it carries cardiovascular risks. The mineral calcium has at best reduced regrowth by about 20 percent.
The DFMO-sulindac combination more than doubled those rates in some cases and was especially powerful in preventing advanced polyps most likely to lead to cancer.
"That's the real breakthrough," Gerner said. "We have shown for the first time that a combination strategy can dramatically reduce this threat for the patients at highest risk.
"Further testing will tell us if this therapy might be useful for others at risk — those who have a family history of colon cancer, but have not yet developed polyps," Gerner added.
One of the key drugs in the new therapy — DFMO, or difluoromethylornithine — is a synthetic amino acid known to interfere with the carcinogenic process. But used alone, it proved toxic at doses needed for treating advanced cancer. By combining it with the NSAID sulindac, the research team was able to cut the DFMO to one-fiftieth of that dose, all but eliminating toxic effects.
"There is a great hope that we will be able to prevent colon cancer effectively using this method," Meyskens said. "We had not been able to do this before due to the high toxicity of available therapies."
The study involved about 300 patients who had at least one colon polyp within the previous five years. They were given either the daily combination DFMO (500 milligrams) and sulindac (150 mg), or a placebo.
After three years, the risk of a recurrent polyp dropped from 41.1 percent in the placebo group to 12.3 percent with treatment — a 70 percent reduction.
Even more striking, the risk in patients with advanced polyps dropped from 8.5 percent in the placebo group to 0.7 percent in the treatment group — a 92 percent reduction.
And for those in the most danger — patients with multiple previous polyps — the rate of re-growth plunged from 13.2 percent in the placebo group to 0.7 percent in the treatment group — a 95 percent reduction.
The results were so dramatic that the trial was stopped early and the results released.
Finally, an analysis of side effects and toxicity found no significant difference between the treatment and placebo groups.
The study was funded in part by the National Cancer Institute's Specialized Program of Research Excellence in GI Cancers.
The Arizona Cancer Center is one of only five institutions nationwide to receive a GI SPORE grant. Originally funded in 2002, it is the largest new grant awarded to the University of Arizona College of Medicine in the past 10 years. It was renewed in 2007 for another five years and funded at $12 million.
On StarNet: Find more cancer resources, including information on screening and prevention, at go.azstarnet.com/cancer.
FDA soon may support biomarker tests
[Source: Ann Fernholm, Chronicle Staff Writer] - The Food and Drug Administration is poised to throw its support behind a powerful new method of predicting the safety of experimental drugs, a step that could help pharmaceutical companies bring treatments to market more quickly - and reduce patients' risk.
The process being considered uses seven indicators - known as biomarkers - that signal kidney injury when found in the urine of test subjects.
"Today, the FDA gives approval for a new drug or device, but there has previously been no way to obtain approval for a new and better way to test a drug for its safety," said Raymond Woosley, president and CEO of the nonprofit Critical Path Institute, which is working with the FDA to safely speed drug development.
Currently, experimental drugs are tested in animals before being taken to human clinical trails. But animals' reactions aren't always the best predictor of whether substances will be safe for humans. Drugs harmless to animals can hurt humans, and vice versa. If a drug toxic to the kidneys passes animal tests today, the damage might not show up until it is too late.
"Using current tests, you have lost about 70 percent of the kidney function before you pick it up," says William Mattes, director of toxicology at the Critical Path Institute in Tucson.
The new biomarker process has the potential to save a patient's kidneys.
The ultimate goal of the pharmaceutical industry is to have a range of such marker tests that would signal dangerous side effects like heart failure, liver damage or cancer. Samples of blood, urine or saliva, for example, would be taken from participants in a clinical trial. If certain biomarkers indicated the patient was at risk, the trial could be stopped before any major damage occurs.
Seventeen companies have joined the research into biomarkers at the Critical Path Institute. These include giants like Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck and Co. and Pfizer. The companies contribute their expertise but, according to Woosley, the institute does not accept commercial funding.
Initially, the seven biomarker testing processes will be qualified by the FDA for use in preclinical animal studies, and only as a complement to current tests.
"This qualification process allows the industry to have an accurate view of the application of these biomarkers in drug development. They are not replacing anything that is done today. But the goal, as we gather more and more information, is to eventually be able to include them in clinical trials," said Federico Goodsaid, senior staff scientist at the genomics group at the FDA Office of Clinical Pharmacology.
Goodsaid is responsible for the development of the FDA's biomarker qualification pilot process, which began about a year ago when 23 potential biomarkers for kidney damage were submitted to the federal agency. The evaluation process at the Critical Path Institute has since selected the seven most efficient ones.
Named for the risky period when a drug is taken from the preclinical stage into clinical trials, the Critical Path Institute was founded two years ago by the FDA in collaboration with University of Arizona and Menlo Park's SRI International to break a worrying trend within the pharmaceutical industry: In the past decade the number of innovative therapies submitted for FDA approval dropped by 50 percent, but the cost of drug development increased dramatically.
Meanwhile, scares like the one associated with the painkiller Vioxx, which turned out to cause heart attacks and strokes, have further fueled this trend.
Unique for the Critical Path Institute is that FDA is a cofounder. Today, the European Medicines Agency - an agency similar to the FDA - also participates as an adviser. The agency is expected to qualify the seven biomarker testing method simultaneously with FDA.
"This is the first time they have coordinated their decisions," Mattes said.
Sidney Wolfe, director of the health research group at Public Citizen, a nonprofit public interest organization, supports the use of biomarkers as long as they are properly validated. But he is critical of the FDA's attitude toward present drug safety tests.
"Findings of toxicity in the currently required animal tests are not taken seriously enough by companies or by the FDA," Wolfe said.
He cites two recent examples of drugs in trouble, both of which showed toxicity in laboratory animals: the diabetes drug Avandia from GlaxoSmithKline and Vytorin from Schering-Plough and Merck, a cholesterol-lowering medication.
"Avandia showed evidence of heart damage in animal studies and, for Vytorin, tests showed serious toxicity in laboratory animals, regardless of how low a dose of this combination drug was used," says Wolfe.
The official announcement of the qualification of the seven biomarkers for kidney injury is expected from the FDA any day.
"It is in a very advanced stage of that process," Goodsaid said. "We should have some news soon."
What are biomarkers?
A biomarker is an indicator that can be used to test a biological function. Some biomarkers turn up when organs are injured and cells within the damaged tissue release substances into the blood, urine or saliva. These substances can then be used to detect dangerous side effects.
E-mail Ann Fernholm at afernholm@sfchronicle.com.
The process being considered uses seven indicators - known as biomarkers - that signal kidney injury when found in the urine of test subjects.
"Today, the FDA gives approval for a new drug or device, but there has previously been no way to obtain approval for a new and better way to test a drug for its safety," said Raymond Woosley, president and CEO of the nonprofit Critical Path Institute, which is working with the FDA to safely speed drug development.
Currently, experimental drugs are tested in animals before being taken to human clinical trails. But animals' reactions aren't always the best predictor of whether substances will be safe for humans. Drugs harmless to animals can hurt humans, and vice versa. If a drug toxic to the kidneys passes animal tests today, the damage might not show up until it is too late.
"Using current tests, you have lost about 70 percent of the kidney function before you pick it up," says William Mattes, director of toxicology at the Critical Path Institute in Tucson.
The new biomarker process has the potential to save a patient's kidneys.
The ultimate goal of the pharmaceutical industry is to have a range of such marker tests that would signal dangerous side effects like heart failure, liver damage or cancer. Samples of blood, urine or saliva, for example, would be taken from participants in a clinical trial. If certain biomarkers indicated the patient was at risk, the trial could be stopped before any major damage occurs.
Seventeen companies have joined the research into biomarkers at the Critical Path Institute. These include giants like Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck and Co. and Pfizer. The companies contribute their expertise but, according to Woosley, the institute does not accept commercial funding.
Initially, the seven biomarker testing processes will be qualified by the FDA for use in preclinical animal studies, and only as a complement to current tests.
"This qualification process allows the industry to have an accurate view of the application of these biomarkers in drug development. They are not replacing anything that is done today. But the goal, as we gather more and more information, is to eventually be able to include them in clinical trials," said Federico Goodsaid, senior staff scientist at the genomics group at the FDA Office of Clinical Pharmacology.
Goodsaid is responsible for the development of the FDA's biomarker qualification pilot process, which began about a year ago when 23 potential biomarkers for kidney damage were submitted to the federal agency. The evaluation process at the Critical Path Institute has since selected the seven most efficient ones.
Named for the risky period when a drug is taken from the preclinical stage into clinical trials, the Critical Path Institute was founded two years ago by the FDA in collaboration with University of Arizona and Menlo Park's SRI International to break a worrying trend within the pharmaceutical industry: In the past decade the number of innovative therapies submitted for FDA approval dropped by 50 percent, but the cost of drug development increased dramatically.
Meanwhile, scares like the one associated with the painkiller Vioxx, which turned out to cause heart attacks and strokes, have further fueled this trend.
Unique for the Critical Path Institute is that FDA is a cofounder. Today, the European Medicines Agency - an agency similar to the FDA - also participates as an adviser. The agency is expected to qualify the seven biomarker testing method simultaneously with FDA.
"This is the first time they have coordinated their decisions," Mattes said.
Sidney Wolfe, director of the health research group at Public Citizen, a nonprofit public interest organization, supports the use of biomarkers as long as they are properly validated. But he is critical of the FDA's attitude toward present drug safety tests.
"Findings of toxicity in the currently required animal tests are not taken seriously enough by companies or by the FDA," Wolfe said.
He cites two recent examples of drugs in trouble, both of which showed toxicity in laboratory animals: the diabetes drug Avandia from GlaxoSmithKline and Vytorin from Schering-Plough and Merck, a cholesterol-lowering medication.
"Avandia showed evidence of heart damage in animal studies and, for Vytorin, tests showed serious toxicity in laboratory animals, regardless of how low a dose of this combination drug was used," says Wolfe.
The official announcement of the qualification of the seven biomarkers for kidney injury is expected from the FDA any day.
"It is in a very advanced stage of that process," Goodsaid said. "We should have some news soon."
What are biomarkers?
A biomarker is an indicator that can be used to test a biological function. Some biomarkers turn up when organs are injured and cells within the damaged tissue release substances into the blood, urine or saliva. These substances can then be used to detect dangerous side effects.
E-mail Ann Fernholm at afernholm@sfchronicle.com.
Wednesday, April 16, 2008
New Method Can Rapidly ID Optimal Drug Cocktails
[Source: ScienceDaily] — UCLA researchers have developed a feedback control scheme that can search for the most effective drug combinations to treat a variety of conditions, including cancers and infections. The discovery could play a significant role in facilitating new clinical drug-cocktail trials.
The best known use of drug cocktails has been in the fight against HIV, the virus that causes AIDS. Drug cocktails also have been used to combat several types of cancer. Often, drugs that might not be effective in combating diseases individually do much better in combination.
With the use of the new closed-loop feedback control scheme, an approach guided by a stochastic search algorithm, researchers at the UCLA Henry Samueli School of Engineering and Applied Science and UCLA's Jonsson Comprehensive Cancer Center have devised an invaluable means of identifying potent drug combinations fast and efficiently. Their findings appear in the March 17 online version of the journal Proceedings of the National Academy of Sciences.
It has long been a difficult challenge for clinical researchers to determine the optimal dose of individual drugs used in combination. For example, a researcher testing 10 different concentrations of six drugs in every possible arrangement would be faced with 1 million potential combinations.
"With the development of this optimization method, we've overcome a major roadblock," said study author Chih-Ming Ho, UCLA's Ben Rich-Lockheed Martin Professor and a member of the National Academy of Engineering. "There have always been too many choices and too many combinations to sort through. It was like finding a needle in a haystack."
In one test case, the research team examined how to best prevent a viral infection of host cells. Using the closed-loop optimization scheme, they were able to identify, out of 100,000 possible combinations, the drug cocktails that completely inhibited viral infection after only about a dozen trials. In addition, they found that total inhibition of the virus occurred at much lower drug doses than would be necessary if the drugs were used alone; in fact, the concentrations of the drugs were only about 10 percent of that required when used individually.
"Viruses grow very rapidly and change rapidly as well. Because of that, a virus can become resistant to a particular drug," said Genhong Cheng, a member of the research team at the UCLA Center for Cell Control and UCLA's Jonsson Comprehensive Cancer Center. "This is why it's so important to be able to use a combination of more than one drug. If the virus mutates to become resistant to one drug, it is still sensitive to the other drugs."
Drug combinations can also be used effectively to inhibit infectious diseases because resistance to a single drug is very common, according to Ren Sun, UCLA professor of molecular and medical pharmacology and a member of the research team.
"If we can apply multiple drugs against one infectious agent, it probably will prevent the occurrence of drug resistance," said Sun, who is also a researcher at the Jonsson Cancer Center. "But, of course, when you use multiple drugs, side effects will be strong. With this model, there is a way to optimize the combination to reduce the side effects while maintaining efficacy that will be very beneficial."
"What the search scheme does is it tries to detect trends for optimal output," said Pak Wong, a former UCLA graduate student who participated in the study and is now an assistant professor of mechanical engineering at the University of Arizona. "Basically, the algorithm sees a trend and a direction and drives the trend in that direction. It's like mountain climbing and finding a way to get to the peak. So you keep going, and soon you rapidly find the peak while being guided by a smart search scheme."
In an example used to illustrate the prevention of viral infection of host cells, researchers started with arbitrarily chosen dosages of the drugs. The percentage of non-infected cells under this initial drug-cocktail treatment was fed into the stochastic search algorithm, which essentially helps guide a random search process. The algorithm then suggested the next drug concentrations for producing a higher percentage of non-infected cells. This closed-loop feedback control scheme is carried out continuously until the best combination is found. Randomness is built into the search decision, preventing the trap at local optimum levels and allowing the search process to continue until the optimal drug cocktail is identified.
The model also provides an alternative approach to studying cellular functions. Molecular biologists can identify all the players of a particular regulatory pathway in order to decipher how to block or augment that pathway. Cells are complex systems with many redundant functions, and it is difficult to predict how a cell will respond to multiple stimulations at one time. The model overlooks these details and lets the system determine what works best for itself. If researchers are more interested in how the cellular network functions, this approach can provide an initial bird's-eye view, but it also allows them to home in on the important molecular activities controlled by the best drug combinations.
This search scheme is an extremely effective and versatile tool that can be applied to combat numerous diseases, including cancer, the researchers say, and its multidimensional properties will likely make it useful in a wide variety of additional situations.
The next steps are animal and clinical testing.
The study was funded and supported by the Center for Cell Control, a nanomedicine development center funded by the National Institutes of Health through the Roadmap for Medical Research, and by the Institute for Cell Mimetic Space Exploration, a NASA-sponsored institute.
Adapted from materials provided by University of California - Los Angeles, via EurekAlert!, a service of AAAS.
The best known use of drug cocktails has been in the fight against HIV, the virus that causes AIDS. Drug cocktails also have been used to combat several types of cancer. Often, drugs that might not be effective in combating diseases individually do much better in combination.
With the use of the new closed-loop feedback control scheme, an approach guided by a stochastic search algorithm, researchers at the UCLA Henry Samueli School of Engineering and Applied Science and UCLA's Jonsson Comprehensive Cancer Center have devised an invaluable means of identifying potent drug combinations fast and efficiently. Their findings appear in the March 17 online version of the journal Proceedings of the National Academy of Sciences.
It has long been a difficult challenge for clinical researchers to determine the optimal dose of individual drugs used in combination. For example, a researcher testing 10 different concentrations of six drugs in every possible arrangement would be faced with 1 million potential combinations.
"With the development of this optimization method, we've overcome a major roadblock," said study author Chih-Ming Ho, UCLA's Ben Rich-Lockheed Martin Professor and a member of the National Academy of Engineering. "There have always been too many choices and too many combinations to sort through. It was like finding a needle in a haystack."
In one test case, the research team examined how to best prevent a viral infection of host cells. Using the closed-loop optimization scheme, they were able to identify, out of 100,000 possible combinations, the drug cocktails that completely inhibited viral infection after only about a dozen trials. In addition, they found that total inhibition of the virus occurred at much lower drug doses than would be necessary if the drugs were used alone; in fact, the concentrations of the drugs were only about 10 percent of that required when used individually.
"Viruses grow very rapidly and change rapidly as well. Because of that, a virus can become resistant to a particular drug," said Genhong Cheng, a member of the research team at the UCLA Center for Cell Control and UCLA's Jonsson Comprehensive Cancer Center. "This is why it's so important to be able to use a combination of more than one drug. If the virus mutates to become resistant to one drug, it is still sensitive to the other drugs."
Drug combinations can also be used effectively to inhibit infectious diseases because resistance to a single drug is very common, according to Ren Sun, UCLA professor of molecular and medical pharmacology and a member of the research team.
"If we can apply multiple drugs against one infectious agent, it probably will prevent the occurrence of drug resistance," said Sun, who is also a researcher at the Jonsson Cancer Center. "But, of course, when you use multiple drugs, side effects will be strong. With this model, there is a way to optimize the combination to reduce the side effects while maintaining efficacy that will be very beneficial."
"What the search scheme does is it tries to detect trends for optimal output," said Pak Wong, a former UCLA graduate student who participated in the study and is now an assistant professor of mechanical engineering at the University of Arizona. "Basically, the algorithm sees a trend and a direction and drives the trend in that direction. It's like mountain climbing and finding a way to get to the peak. So you keep going, and soon you rapidly find the peak while being guided by a smart search scheme."
In an example used to illustrate the prevention of viral infection of host cells, researchers started with arbitrarily chosen dosages of the drugs. The percentage of non-infected cells under this initial drug-cocktail treatment was fed into the stochastic search algorithm, which essentially helps guide a random search process. The algorithm then suggested the next drug concentrations for producing a higher percentage of non-infected cells. This closed-loop feedback control scheme is carried out continuously until the best combination is found. Randomness is built into the search decision, preventing the trap at local optimum levels and allowing the search process to continue until the optimal drug cocktail is identified.
The model also provides an alternative approach to studying cellular functions. Molecular biologists can identify all the players of a particular regulatory pathway in order to decipher how to block or augment that pathway. Cells are complex systems with many redundant functions, and it is difficult to predict how a cell will respond to multiple stimulations at one time. The model overlooks these details and lets the system determine what works best for itself. If researchers are more interested in how the cellular network functions, this approach can provide an initial bird's-eye view, but it also allows them to home in on the important molecular activities controlled by the best drug combinations.
This search scheme is an extremely effective and versatile tool that can be applied to combat numerous diseases, including cancer, the researchers say, and its multidimensional properties will likely make it useful in a wide variety of additional situations.
The next steps are animal and clinical testing.
The study was funded and supported by the Center for Cell Control, a nanomedicine development center funded by the National Institutes of Health through the Roadmap for Medical Research, and by the Institute for Cell Mimetic Space Exploration, a NASA-sponsored institute.
Adapted from materials provided by University of California - Los Angeles, via EurekAlert!, a service of AAAS.
Multiple Myeloma Research Consortium and Sunesis Pharmaceuticals Present Data On SNS-032 At American Association of Cancer Research Annual Meeting
[Source Genetic Engineering News] - The Multiple Myeloma Research Consortium (MMRC) in collaboration with Sunesis Pharmaceuticals presented preclinical data on the activity of Sunesis' cell cycle inhibitor, SNS-032, in multiple myeloma cell assays and animal models. The data was presented orally at the 2008 Annual Meeting of the American Association of Cancer Research.
Suzanne Trudel, MD, Assistant Professor, University Health Network (UHN) in Toronto, Canada, and Project Leader for the MMRC Validation Team, which performed the studies, presented data showing that SNS-032 demonstrated growth inhibitory effects in different multiple myeloma cell lines as well as myeloma cells prepared from patient samples. In addition, SNS-032 demonstrated activity in a transgenic animal model with multiple myeloma characteristics similar to those observed in humans. These studies, resulting from extensive collaborative efforts between the MMRC, Emory University's Winship Cancer Institute and Sunesis demonstrated preclinical, single-agent activity of SNS-032 in multiple myeloma and support its further investigation as a potential therapeutic candidate. SNS-032, a potent and selective inhibitor of cyclin-dependent kinases (CDKs) 2, 7 and 9, is currently in a Phase 1 clinical trial in patients with chronic lymphocytic leukemia (CLL) or multiple myeloma.
"Sunesis is proud to collaborate with the MMRC and the Validation Team to advance this important clinical program in the quest for a cure for multiple myeloma. It highlights the importance of collaborations between industry and oncology field experts in order to more rapidly and appropriately evaluate new treatments for cancer therapy," said Rachael Hawtin, PhD, Associate Director, Biology, Sunesis.
The MMRC Validation Team, composed of leading myeloma scientists from the Dana-Farber Cancer Institute, Mayo Clinic-Scottsdale, H. Lee Moffitt Cancer Center and UHN, tests compounds in a variety of multiple myeloma cell-based systems and animal models. The team represents a unique research and development model, typically not included in foundation activities, with the major goal of prioritizing compounds to enter myeloma clinical trials by testing their preclinical activity in myeloma specific systems.
"The team is very encouraged by the success of the first project to enter the MMRC validation model and the selection of this research as an oral presentation at the AACR. The results demonstrate modest single agent activity in mice," says Dr. Trudel
Suzanne Trudel, MD, Assistant Professor, University Health Network (UHN) in Toronto, Canada, and Project Leader for the MMRC Validation Team, which performed the studies, presented data showing that SNS-032 demonstrated growth inhibitory effects in different multiple myeloma cell lines as well as myeloma cells prepared from patient samples. In addition, SNS-032 demonstrated activity in a transgenic animal model with multiple myeloma characteristics similar to those observed in humans. These studies, resulting from extensive collaborative efforts between the MMRC, Emory University's Winship Cancer Institute and Sunesis demonstrated preclinical, single-agent activity of SNS-032 in multiple myeloma and support its further investigation as a potential therapeutic candidate. SNS-032, a potent and selective inhibitor of cyclin-dependent kinases (CDKs) 2, 7 and 9, is currently in a Phase 1 clinical trial in patients with chronic lymphocytic leukemia (CLL) or multiple myeloma.
"Sunesis is proud to collaborate with the MMRC and the Validation Team to advance this important clinical program in the quest for a cure for multiple myeloma. It highlights the importance of collaborations between industry and oncology field experts in order to more rapidly and appropriately evaluate new treatments for cancer therapy," said Rachael Hawtin, PhD, Associate Director, Biology, Sunesis.
The MMRC Validation Team, composed of leading myeloma scientists from the Dana-Farber Cancer Institute, Mayo Clinic-Scottsdale, H. Lee Moffitt Cancer Center and UHN, tests compounds in a variety of multiple myeloma cell-based systems and animal models. The team represents a unique research and development model, typically not included in foundation activities, with the major goal of prioritizing compounds to enter myeloma clinical trials by testing their preclinical activity in myeloma specific systems.
"The team is very encouraged by the success of the first project to enter the MMRC validation model and the selection of this research as an oral presentation at the AACR. The results demonstrate modest single agent activity in mice," says Dr. Trudel
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